University of Manchester
EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF RHEUMATOID ARTHRITIS WITH SYNTHETIC AND BIOLOGICAL DISEASE-MODIFYING ANTIRHEUMATIC DRUGS: 2016 UPDATEJosef S. Smolen,1,2* Robert Landewé,3* Johannes Bijlsma,4 Gerd Burmester,5 Katerina Chatzidionysiou,6 Bernard Combe,7 Maxime Dougados,8 Jackie Nam,9 Sofia Ramiro,10 Marieke Scholte,11 Ronald van Vollenhoven,3 Daniel Aletaha,1 Martin Aringer,12 Maarten Boers,13 Chris Buckley,14 Vivian Bykerk,15 Frank Buttgereit,5 Mario Cardiel,16 Maurizio Cutolo,17 Eijk-Yvonne Hustings,18 Paul Emery,9 Axel Finckh,19 Cem Gabay,19 Juan Gomez-Reino,20 Laure Gossec,21 Jacques-Eric Gottenberg,22 Mieke Hazes,23 Tom Huizinga,10 Meghna Jani,24 Dmitry Karateev,25 Marios Kouloumas,26 Tore Kvien,27 Zhanguo Li,28 Xavier Mariette,29 Iain McInnes,30 Eduardo Mysler,31 Peter Nash,32 Karel Pavelka,33 Gyula Poór,34 Christophe Richez,35 Piet van Riel,36 Andrea Rubbert-Roth,37 Kenneth Saag,38 Jose da Silva,39 Tanja Stamm,40 Tsutomu Takeuchi,41 René Westhovens,42 Martinus de Wit,43 Désirée van der Heijde101Division of Rheumatology, Department of Medicine 3, Medical University of Vienna and 22nd Department of Medicine, Hietzing Hospital, Vienna, Austria; 3Amsterdam Rheumatology & Immunology Center, Amsterdam, & Zuyderland Medical Center, Heerlen, The Netherlands; 4Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht Utrecht, The Netherlands; 5Department of Rheumatology and Clinical Immunology, Charité - University Medicine Berlin, Free University and Humboldt University Berlin, Germany; 6Rheumatology Department, Karolinska Institute, Stockholm, Sweden; 7Rheumatology Department, Lapeyronie Hospital, Montpellier University, UMR 5535, Montpellier, France; 8Rhumatologie B, Hopital Cochin, 27 rue du Fbg Saint-Jacques, 75014 Paris, France; 9NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, United Kingdom; 10Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; ; 12Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universit?tsklinikum Carl Gustav Carus, Technische Universit?t Dresden, Germany; 13Department of Epidemiology and?Biostatistics, VU University Medical Center, Amsterdam,?The Netherlands; 14Birmingham NIHR Wellcome Trust Clinical Research Facility, Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom; 15Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA; Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; 16Centro de Investigación Clínica de Morelia SC, Michoacán, México; 17Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy; Department of Patient & Care and Department of Rheumatology, University of Maastricht, the Netherlands; 19Division of Rheumatology, University Hospitals of Geneva, Switzerland; 20Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain; 21Sorbonne Universités, Pitié Salpêtrière Hospital, Department of Rheumatology, Paris, France; 22Strasbourg University Hospital and University of Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg, France; 23Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; 24Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, United Kingdom; 25V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation; 26European League Against Rheumatism, Zurich, Switzerland, and Cyprus League against Rheumatism, Nikosia, Cyprus; 27Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; 28Department of rheumatology and immunology, Beijing University People's Hospital, China; 29Université Paris-Sud, Assistance Publique-H?pitaux de Paris, H?pitaux Universitaires Paris-Sud, INSERM U1184, Center for Immunology of viral Infections and Autoimmune Diseases (IMVA), Le Kremlin Bicêtre, France; 30Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Scotland; 31Organización Médica de Investigación, Buenos Aires, Argentina; 32Department of Medicine, University of Queensland, Australia; 33Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic; 34National Institute of Rheumatology and Physiotherapy, Semmelweis University, Budapest; 35Rheumatology Department,?FHU ACRONIM,?Pellegrin Hospital and?UMR CNRS 5164,?Bordeaux University,?Bordeaux, France; 36Department of Rheumatology, Bernhoven, Uden, Netherlands; 37University of Cologne, Cologne, Germany; 38Department of Medicine, Division of Rheumatology, University of Alabama at Birmingham, Birmingham, USA: 39Servi?o de Reumatologia, Centro Hospitalar e Universitário de Coimbra Praceta Mota Pinto, Coimbra, Portugal; 40Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria; 41Keio University School of Medicine, Keio University Hospital, Tokyo, Japan; 42Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven; Rheumatology, University Hospitals Leuven, Leuven, Belgium; 43Department Medical Humanities, VU Medical Centre, Van der Boechorststraat 7, Amsterdam, The Netherlands*Joint first authors; JS and RL contributed equally to the development of the recommendations and this manuscriptCorrespondence:Josef Smolen, MD, Div. of Rheumatology, Dept. of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. T: +43-1-40400-43000; F: +43-1-40400-43060; e-mail: josef.smolen@wienkav.at; josef.smolen@meduniwien.ac.at Short title: 2016 Update of EULAR RA management recommendationsAbstractRecent insights in RA necessitated updating the EULAR RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (versus 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) DMARDs (methotrexate [MTX], leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (TNF-inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs; targeted synthetic (ts) DMARDs (Janus kinase [Jak] inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission, as defined by ACR-EULAR Boolean or index criteria, or low disease activity are discussed. Targeting imaging remission has no advantages, but economic disadvantages. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25mg/week) plus short-term GC, aiming at >50% improvement within 3- and target attainment within 6 months. If this fails stratification is recommended. Without unfavorable prognostic markers, switching to -or adding- another csDMARDs (plus short-term GC) is suggested. In the presence of unfavorable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered.For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR’s most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.tThe management of rheumatoid arthritis (RA) has changed dramatically over the past thirty years. Few therapeutic agents existed then, which were either minimally or not efficacious, because of toxicity and the fact that optimal dosing and onset of action had not yet been elucidated for some agents.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPldpbHNrZSBLUjwvQXV0aG9yPjxZZWFyPjE5OTA8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPldpbHNrZSBLUjwvQXV0aG9yPjxZZWFyPjE5OTA8L1llYXI+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ADDIN EN.CITE.DATA 1-4 Available therapies were started late rather than early in the course of the disease.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNjaHVtYWNoZXIgSFI8L0F1dGhvcj48WWVhcj4xOTkzPC9Z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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNjaHVtYWNoZXIgSFI8L0F1dGhvcj48WWVhcj4xOTkzPC9Z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ADDIN EN.CITE.DATA 5;6 Early arthritis clinics were emerging,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkh1aXppbmdhPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48
UmVjTnVtPjQzPC9SZWNOdW0+PElEVGV4dD5Dcml0ZXJpYSBmb3IgZWFybHkgcmhldW1hdG9pZCBh
cnRocml0aXM6IEZyb20gQmF5ZXMmYXBvczsgbGF3IHJldmlzaXRlZCB0byBuZXcgdGhvdWdodHMg
b24gcGF0aG9nZW5lc2lzLiAoQ29uZmVyZW5jZSBzdW1tYXJ5KTwvSURUZXh0PjxNREwgUmVmX1R5
cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjQzPC9SZWZf
SUQ+PFRpdGxlX1ByaW1hcnk+Q3JpdGVyaWEgZm9yIGVhcmx5IHJoZXVtYXRvaWQgYXJ0aHJpdGlz
OiBGcm9tIEJheWVzJmFwb3M7IGxhdyByZXZpc2l0ZWQgdG8gbmV3IHRob3VnaHRzIG9uIHBhdGhv
Z2VuZXNpcy4gKENvbmZlcmVuY2Ugc3VtbWFyeSk8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5IdWl6aW5nYSxXLkouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NYWNo
b2xkLEsuUC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJyZWVkdmVsZCxGLkMu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5MaXBza3ksUC5FPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TbW9sZW4sSi5TLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRl
X1ByaW1hcnk+MjAwMjwvRGF0ZV9QcmltYXJ5PjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50
PjxTdGFydF9QYWdlPjExNTU8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjExNTk8L0VuZF9QYWdlPjxQ
ZXJpb2RpY2FsPkFydGhyaXRpcyBSaGV1bS48L1BlcmlvZGljYWw+PFZvbHVtZT40NjwvVm9sdW1l
PjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5hbWU9IlN5c3RlbSI+QXJ0aHJpdGlzIFJoZXVtLjwv
Zj48L1paX0pvdXJuYWxTdGRBYmJyZXY+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48
L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj52YW4gZGVyIEhvcnN0LUJydWluc21hPC9BdXRob3I+
PFllYXI+MTk5ODwvWWVhcj48UmVjTnVtPjQwPC9SZWNOdW0+PElEVGV4dD5EaWFnbm9zaXMgYW5k
IGNvdXJzZSBvZiBlYXJseSBvbnNldCBhcnRocml0aXM6IHJlc3VsdHMgb2YgYSBzcGVjaWFsIGVh
cmx5IGFydGhyaXRpcyBjbGluaWMgY29tcGFyZWQgdG8gcm91dGluZSBwYXRpZW50IGNhcmUuPC9J
RFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBl
PjxSZWZfSUQ+NDA8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5EaWFnbm9zaXMgYW5kIGNvdXJzZSBv
ZiBlYXJseSBvbnNldCBhcnRocml0aXM6IHJlc3VsdHMgb2YgYSBzcGVjaWFsIGVhcmx5IGFydGhy
aXRpcyBjbGluaWMgY29tcGFyZWQgdG8gcm91dGluZSBwYXRpZW50IGNhcmUuPC9UaXRsZV9Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIGRlciBIb3JzdC1CcnVpbnNtYSxJLkUuPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TcGV5ZXIsSS48L0F1dGhvcnNfUHJpbWFyeT48QXV0
aG9yc19QcmltYXJ5PlZpc3NlcixILjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
QnJlZWR2ZWxkLEYuQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkhhemVzLEou
TS5XLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MTk5ODwvRGF0ZV9QcmltYXJ5PjxS
ZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjEwODQ8L1N0YXJ0X1BhZ2U+
PEVuZF9QYWdlPjEwODg8L0VuZF9QYWdlPjxQZXJpb2RpY2FsPkJyLkouUmhldW1hdG9sLjwvUGVy
aW9kaWNhbD48Vm9sdW1lPjM3PC9Wb2x1bWU+PFpaX0pvdXJuYWxTdGRBYmJyZXY+PGYgbmFtZT0i
U3lzdGVtIj5Cci5KLlJoZXVtYXRvbC48L2Y+PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9Xb3Jr
Zm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRob3I+RW1lcnk8
L0F1dGhvcj48WWVhcj4xOTkxPC9ZZWFyPjxSZWNOdW0+MzEyMTwvUmVjTnVtPjxJRFRleHQ+V2h5
IGVhcmx5IGFydGhyaXRpcyBjbGluaWNzPzwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwi
PjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjMxMjE8L1JlZl9JRD48VGl0bGVf
UHJpbWFyeT5XaHkgZWFybHkgYXJ0aHJpdGlzIGNsaW5pY3M/PC9UaXRsZV9QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+RW1lcnksUC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pkdv
dWdoLEEuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4xOTkxLzg8L0RhdGVfUHJpbWFy
eT48S2V5d29yZHM+QW1idWxhdG9yeSBDYXJlIEZhY2lsaXRpZXM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5hbmFseXNpczwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdv
cmRzPkJpb21hcmtlcnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5jb21wbGljYXRpb25zPC9LZXl3b3Jk
cz48S2V5d29yZHM+RG5hPC9LZXl3b3Jkcz48S2V5d29yZHM+RG5hLFZpcmFsPC9LZXl3b3Jkcz48
S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+bWljcm9iaW9sb2d5PC9LZXl3b3Jk
cz48S2V5d29yZHM+UGF0aWVudCBFZHVjYXRpb24gYXMgVG9waWM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5Qcm9nbm9zaXM8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5PC9LZXl3b3Jkcz48UmVwcmlu
dD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4yNDE8L1N0YXJ0X1BhZ2U+PEVuZF9Q
YWdlPjI0MjwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QnIuSi5SaGV1bWF0b2w8L1BlcmlvZGljYWw+
PFZvbHVtZT4zMDwvVm9sdW1lPjxJc3N1ZT40PC9Jc3N1ZT48V2ViX1VSTD5QTToxODYzODE3PC9X
ZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5hbWU9IlN5c3RlbSI+QnIuSi5SaGV1bWF0
b2w8L2Y+PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3Jt
SUQ+PC9NREw+PC9DaXRlPjwvUmVmbWFuPm==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkh1aXppbmdhPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48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ADDIN EN.CITE.DATA 7-9 and their successes fueled reappraisal of the classification criteria then available that focused primarily upon long-standing disease. ADDIN REFMGR.CITE <Refman><Cite><Author>Aletaha D</Author><Year>2005</Year><RecNum>872</RecNum><IDText>The need for new classification criteria for rheumatoid arthritis.</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>872</Ref_ID><Title_Primary>The need for new classification criteria for rheumatoid arthritis.</Title_Primary><Authors_Primary>Aletaha D</Authors_Primary><Authors_Primary>Breedveld FC</Authors_Primary><Authors_Primary>Smolen JS</Authors_Primary><Date_Primary>2005</Date_Primary><Keywords>classification</Keywords><Keywords>Arthritis</Keywords><Reprint>In File</Reprint><Start_Page>3333</Start_Page><End_Page>3336</End_Page><Periodical>Arthritis Rheum</Periodical><Volume>52</Volume><ZZ_JournalFull><f name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>10 A therapeutic target had not yet been defined, because relief of symptoms appeared to be the most important goal and the concept of disease states, such as remission or low disease activity were at best aspirational. ADDIN REFMGR.CITE <Refman><Cite><Author>Emery</Author><Year>1995</Year><RecNum>60</RecNum><IDText>Early rheumatoid arthritis: time to aim for remission?</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>60</Ref_ID><Title_Primary>Early rheumatoid arthritis: time to aim for remission?</Title_Primary><Authors_Primary>Emery,P.</Authors_Primary><Authors_Primary>Salmon,M.</Authors_Primary><Date_Primary>1995</Date_Primary><Reprint>Not in File</Reprint><Start_Page>944</Start_Page><End_Page>947</End_Page><Periodical>Ann.Rheum.Dis.</Periodical><Volume>54</Volume><ZZ_JournalStdAbbrev><f name="System">Ann.Rheum.Dis.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>11 To date, we have available numerous efficacious agents. Among the conventional synthetic (cs) disease modifying antirheumatic drugs (DMARDs) ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen</Author><Year>2014</Year><RecNum>2744</RecNum><IDText>Proposal for a new nomenclature of disease-modifying antirheumatic drugs</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2744</Ref_ID><Title_Primary>Proposal for a new nomenclature of disease-modifying antirheumatic drugs</Title_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>van der Heijde,D.</Authors_Primary><Authors_Primary>Machold,K.P.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>Landewe,R.</Authors_Primary><Date_Primary>2014/1</Date_Primary><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>Disease</Keywords><Keywords>drug therapy</Keywords><Keywords>Gold</Keywords><Keywords>Humans</Keywords><Keywords>Hydroxychloroquine</Keywords><Keywords>Methotrexate</Keywords><Keywords>Molecular Structure</Keywords><Keywords>Rheumatic Diseases</Keywords><Keywords>Rheumatology</Keywords><Keywords>standards</Keywords><Keywords>Sulfasalazine</Keywords><Keywords>Terminology as Topic</Keywords><Reprint>Not in File</Reprint><Start_Page>3</Start_Page><End_Page>5</End_Page><Periodical>Ann Rheum Dis</Periodical><Volume>73</Volume><Issue>1</Issue><Misc_3>annrheumdis-2013-204317 [pii];10.1136/annrheumdis-2013-204317 [doi]</Misc_3><Address>Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, , Vienna , Austria</Address><Web_URL>PM:24072562</Web_URL><ZZ_JournalFull><f name="System">Ann Rheum Dis</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>12 we adopted MTX, upon its optimal use, as the anchor drug; ADDIN REFMGR.CITE <Refman><Cite><Author>Visser</Author><Year>2009</Year><RecNum>1521</RecNum><IDText>Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>1521</Ref_ID><Title_Primary>Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature</Title_Primary><Authors_Primary>Visser,K.</Authors_Primary><Authors_Primary>van der Heijde D.</Authors_Primary><Date_Primary>2009/7</Date_Primary><Keywords>administration & dosage</Keywords><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Drug Administration Routes</Keywords><Keywords>Drug Administration Schedule</Keywords><Keywords>drug therapy</Keywords><Keywords>Humans</Keywords><Keywords>methods</Keywords><Keywords>Methotrexate</Keywords><Keywords>Netherlands</Keywords><Keywords>Odds Ratio</Keywords><Keywords>Patients</Keywords><Keywords>Randomized Controlled Trials as Topic</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>toxicity</Keywords><Reprint>Not in File</Reprint><Start_Page>1094</Start_Page><End_Page>1099</End_Page><Periodical>Ann.Rheum Dis.</Periodical><Volume>68</Volume><Issue>7</Issue><Address>Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. K.Visser@lumc.nl</Address><Web_URL>PM:19033290</Web_URL><ZZ_JournalStdAbbrev><f name="System">Ann.Rheum Dis.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>4 in addition, a number of biological (b) DMARDs have been approved, more recently followed (in many countries) by approval of the first targeted synthetic (ts) DMARD, with more in development. ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen</Author><Year>2016</Year><RecNum>3088</RecNum><IDText>Rheumatoid arthritis</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3088</Ref_ID><Title_Primary>Rheumatoid arthritis</Title_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>McInnes,I.B.</Authors_Primary><Date_Primary>2016/5/3</Date_Primary><Keywords>Algorithms</Keywords><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>Autoantibodies</Keywords><Keywords>Cartilage</Keywords><Keywords>diagnosis</Keywords><Keywords>Disease</Keywords><Keywords>Early Diagnosis</Keywords><Keywords>epidemiology</Keywords><Keywords>genetics</Keywords><Keywords>Immunity</Keywords><Keywords>Infection</Keywords><Keywords>Inflammation</Keywords><Keywords>Patients</Keywords><Keywords>Rheumatology</Keywords><Keywords>Risk</Keywords><Keywords>Risk Factors</Keywords><Keywords>therapy</Keywords><Reprint>Not in File</Reprint><Periodical>Lancet</Periodical><Misc_3>S0140-6736(16)30173-8 [pii];10.1016/S0140-6736(16)30173-8 [doi]</Misc_3><Address>Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria; 2nd Department of Medicine, Hietzing Hospital Vienna, Vienna, Austria. Electronic address: josef.smolen@wienkav.at
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK</Address><Web_URL>PM:27156434</Web_URL><ZZ_JournalFull><f name="System">Lancet</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>13 Today, new classification criteria for RA promote the study of patients earlier in their disease course than beforePFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGEgRDwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
PFJlY051bT4xNTcxPC9SZWNOdW0+PElEVGV4dD5UaGUgMjAxMCBBbWVyaWNhbiBDb2xsZWdlIG9m
IFJoZXVtYXRvbG9neSAvIEV1cm9wZWFuIExlYWd1ZSBBZ2FpbnN0IFJoZXVtYXRpc20gQ2xhc3Np
ZmljYXRpb24gQ3JpdGVyaWEgZm9yIFJoZXVtYXRvaWQgQXJ0aHJpdGlzLjwvSURUZXh0PjxNREwg
UmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjE1
NzE8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5UaGUgMjAxMCBBbWVyaWNhbiBDb2xsZWdlIG9mIFJo
ZXVtYXRvbG9neSAvIEV1cm9wZWFuIExlYWd1ZSBBZ2FpbnN0IFJoZXVtYXRpc20gQ2xhc3NpZmlj
YXRpb24gQ3JpdGVyaWEgZm9yIFJoZXVtYXRvaWQgQXJ0aHJpdGlzLjwvVGl0bGVfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PkFsZXRhaGEgRDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1h
cnk+TmVvZ2kgVDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2lsbWFuIEE8L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZ1bm92aXRzIEo8L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PkZlbHNvbiBEPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5CaW5naGFtIENPIElJSTwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QnJp
bmJhdW0gTjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QnVybWVzdGVyIEc8L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJ5a2VyayBWPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5vaGVuIE08L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PkNvbWJlIEI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkNvc3RlbmJhZGVyIEs8
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkRvdWdhZG9zIE08L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PkVtZXJ5IFA8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkZlcnJhY2lvbGkgRzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF6
ZXMgTTwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SG9iYnMgSzwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SHVpemluZ2EgVDwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+S2F2YW5hdWdoIEE8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PktheSBKPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LdmllbiBUSzwvQXV0aG9y
c19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGFpbmcgVDwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+TWVhc2UgUDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TSYj
eEU5O25hcmQgSEE8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1vcmVsYW5kIEw8
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk5hZGVuIFI8L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlBpbmN1cyBUPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5TbW9sZW4gSlM8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlN0YW5pc2xh
d3NrYS1CaWVybmF0IEU8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlN5bW1vbnMg
RDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+VGFrIFBQPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5VcGNodXJjaCBLPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5WZW5jb3Zza3kgSjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V29s
ZmUgRjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF3a2VyIEc8L0F1dGhvcnNf
UHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTA8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+UmhldW1h
dG9sb2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+Y2xhc3NpZmljYXRpb248L0tleXdvcmRzPjxLZXl3
b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxT
dGFydF9QYWdlPjE1ODA8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjE1ODg8L0VuZF9QYWdlPjxQZXJp
b2RpY2FsPkFubiBSaGV1bSBEaXM8L1BlcmlvZGljYWw+PFZvbHVtZT42OTwvVm9sdW1lPjxaWl9K
b3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFubiBSaGV1bSBEaXM8L2Y+PC9aWl9Kb3VybmFs
RnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1h
bj5=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGEgRDwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+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ADDIN EN.CITE.DATA 14 and recommendations have been developed to treat RA patients via strategic algorithms targeting an optimal outcome, irrespective of the types of available therapies.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN EN.CITE.DATA 15-17 A limited number of measures to assess response in clinical trials and follow disease activity in clinical practice are widely usedPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MTk5Mzwv
WWVhcj48UmVjTnVtPjMxPC9SZWNOdW0+PElEVGV4dD5EZXZlbG9wbWVudCBvZiBhIERpc2Vhc2Ug
YWN0aXZpdHkgc2NvcmUgYmFzZWQgb24ganVkZ2VtZW50IGluIGNsaW5pY2FsIHByYWN0aWNlIGJ5
IHJoZXVtYXRvbG9naXN0cy48L0lEVGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5
cGU+Sm91cm5hbDwvUmVmX1R5cGU+PFJlZl9JRD4zMTwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PkRl
dmVsb3BtZW50IG9mIGEgRGlzZWFzZSBhY3Rpdml0eSBzY29yZSBiYXNlZCBvbiBqdWRnZW1lbnQg
aW4gY2xpbmljYWwgcHJhY3RpY2UgYnkgcmhldW1hdG9sb2dpc3RzLjwvVGl0bGVfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PlZhbiBkZXIgSGVpamRlLEQuTS5GLk0uPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT52YW4mYXBvczt0IEhvZixNLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+dmFuIFJpZWwsUC5MLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1h
cnk+dmFuIGRlIFB1dHRlLEwuQi5BLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MTk5
MzwvRGF0ZV9QcmltYXJ5PjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdl
PjU3OTwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+NTgxPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5KLlJo
ZXVtYXRvbC48L1BlcmlvZGljYWw+PFZvbHVtZT4yMDwvVm9sdW1lPjxaWl9Kb3VybmFsU3RkQWJi
cmV2PjxmIG5hbWU9IlN5c3RlbSI+Si5SaGV1bWF0b2wuPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJl
dj48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0
aG9yPlByZXZvbzwvQXV0aG9yPjxZZWFyPjE5OTU8L1llYXI+PFJlY051bT4xNzwvUmVjTnVtPjxJ
RFRleHQ+TW9kaWZpZWQgZGlzZWFzZSBhY3Rpdml0eSBzY29yZXMgdGhhdCBpbmNsdWRlIHR3ZW50
eS1laWdodC1qb2ludCBjb3VudHMuIERldmVsb3BtZW50IGFuZCB2YWxpZGF0aW9uIGluIGEgcHJv
c3BlY3RpdmUgbG9uZ2l0dWRpbmFsIHN0dWR5IG9mIHBhdGllbnRzIHdpdGggcmhldW1hdG9pZCBh
cnRocml0aXMuPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJu
YWw8L1JlZl9UeXBlPjxSZWZfSUQ+MTc8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5Nb2RpZmllZCBk
aXNlYXNlIGFjdGl2aXR5IHNjb3JlcyB0aGF0IGluY2x1ZGUgdHdlbnR5LWVpZ2h0LWpvaW50IGNv
dW50cy4gRGV2ZWxvcG1lbnQgYW5kIHZhbGlkYXRpb24gaW4gYSBwcm9zcGVjdGl2ZSBsb25naXR1
ZGluYWwgc3R1ZHkgb2YgcGF0aWVudHMgd2l0aCByaGV1bWF0b2lkIGFydGhyaXRpcy48L1RpdGxl
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5QcmV2b28sTS5MLkwuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT52YW4mYXBvczt0IEhvZixNLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1
dGhvcnNfUHJpbWFyeT5LdXBlcixILkguPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT52YW4gZGUgUHV0dGUsTC5CLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52
YW4gUmllbCxQLkwuQy5NLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MTk5NTwvRGF0
ZV9QcmltYXJ5PjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjQ0PC9T
dGFydF9QYWdlPjxFbmRfUGFnZT40ODwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QXJ0aHJpdGlzIFJo
ZXVtLjwvUGVyaW9kaWNhbD48Vm9sdW1lPjM4PC9Wb2x1bWU+PFpaX0pvdXJuYWxTdGRBYmJyZXY+
PGYgbmFtZT0iU3lzdGVtIj5BcnRocml0aXMgUmhldW0uPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJl
dj48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0
aG9yPlNtb2xlbiBKUzwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJlY051bT44MjwvUmVjTnVt
PjxJRFRleHQ+QSBTaW1wbGlmaWVkIERpc2Vhc2UgQWN0aXZpdHkgSW5kZXggZm9yIFJoZXVtYXRv
aWQgQXJ0aHJpdGlzIEZvciBVc2UgSW4gQ2xpbmljYWwgUHJhY3RpY2UuPC9JRFRleHQ+PE1ETCBS
ZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+ODI8
L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5BIFNpbXBsaWZpZWQgRGlzZWFzZSBBY3Rpdml0eSBJbmRl
eCBmb3IgUmhldW1hdG9pZCBBcnRocml0aXMgRm9yIFVzZSBJbiBDbGluaWNhbCBQcmFjdGljZS48
L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TbW9sZW4gSlM8L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PkJyZWVkdmVsZCBGQzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+U2NoaWZmIE1IPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LYWxk
ZW4gSlI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkVtZXJ5IFA8L0F1dGhvcnNf
UHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkViZXJsIEc8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PnZhbiBSaWVsIFBMQ008L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PlR1Z3dlbGwgUDwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwMzwvRGF0ZV9Qcmlt
YXJ5PjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9S
ZXByaW50PjxTdGFydF9QYWdlPjI0NDwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+MjU3PC9FbmRfUGFn
ZT48UGVyaW9kaWNhbD5SaGV1bWF0b2xvZ3k8L1BlcmlvZGljYWw+PFZvbHVtZT40MjwvVm9sdW1l
PjxaWl9Kb3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPlJoZXVtYXRvbG9neTwvZj48L1paX0pv
dXJuYWxGdWxsPjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjxD
aXRlPjxBdXRob3I+QWxldGFoYSBEPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48UmVjTnVtPjc0
NjwvUmVjTnVtPjxJRFRleHQ+QWN1dGUgcGhhc2UgcmVhY3RhbnRzIGFkZCBsaXR0bGUgdG8gY29t
cG9zaXRlIGRpc2Vhc2UgYWN0aXZpdHkgaW5kaWNlcyBmb3IgcmhldW1hdG9pZCBhcnRocml0aXM6
IFZhbGlkYXRpb24gb2YgYSBjbGluaWNhbCBhY3Rpdml0eSBzY29yZTwvSURUZXh0PjxNREwgUmVm
X1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjc0Njwv
UmVmX0lEPjxUaXRsZV9QcmltYXJ5PkFjdXRlIHBoYXNlIHJlYWN0YW50cyBhZGQgbGl0dGxlIHRv
IGNvbXBvc2l0ZSBkaXNlYXNlIGFjdGl2aXR5IGluZGljZXMgZm9yIHJoZXVtYXRvaWQgYXJ0aHJp
dGlzOiBWYWxpZGF0aW9uIG9mIGEgY2xpbmljYWwgYWN0aXZpdHkgc2NvcmU8L1RpdGxlX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5BbGV0YWhhIEQ8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5Pk5lbGwgVlBLPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TdGFtbSBU
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5VZmZtYW5uIE08L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PlBmbHVnYmVpbCBTPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5NYWNob2xkIEs8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNt
b2xlbiBKUzwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwNTwvRGF0ZV9QcmltYXJ5
PjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5PC9LZXl3b3Jk
cz48S2V5d29yZHM+RGlzZWFzZSBQcm9ncmVzc2lvbjwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVh
Y3RpdmUgUHJvdGVpbjwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5d29yZHM+
PEtleXdvcmRzPmFuYWx5c2lzPC9LZXl3b3Jkcz48S2V5d29yZHM+QW5hbHlzaXMgb2YgVmFyaWFu
Y2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGlu
IEZpbGU8L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+Ujc5NjwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+Ujgw
NjwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QXJ0aHJpdGlzIFJlczwvUGVyaW9kaWNhbD48Vm9sdW1l
Pjc8L1ZvbHVtZT48WlpfSm91cm5hbEZ1bGw+PGYgbmFtZT0iU3lzdGVtIj5BcnRocml0aXMgUmVz
PC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01E
TD48L0NpdGU+PC9SZWZtYW4+
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MTk5Mzwv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ADDIN EN.CITE.DATA 18-21 and the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have jointly developed a new definition for remission which provide an optimal clinical outcome and can be achieved in a significant proportion of patients in trials and practice.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA 22 Attaining remission according to these criteria, index-based or Boolean, will prevent joint destruction or at least progression of joint damage irrespective of residual subclinical changes,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkthdmFuYXVnaDwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkthdmFuYXVnaDwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN EN.CITE.DATA 23;24 optimize physical function, improve quality of life and work capacity,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhZG5lcjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhZG5lcjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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==
ADDIN EN.CITE.DATA 25;26 and reduce comorbidity risks.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlByb3ZhbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlByb3ZhbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA 27;28 With this recent evolution of evidence supporting stringent disease control to improve outcomes, interest in purely symptomatic drugs has significantly decreased today and disease modification has become the pivotal attribute of all modern drugs and treatment strategies. Disease modification is an amalgam of characteristics: relief of signs and symptoms; normalization -or at least important improvement - of impairment in physical function, quality of life and social and work capacity; and – as the foremost distinguishing characteristic of DMARDs compared to symptomatic agents – inhibition of structural damage to cartilage and bone. Therefore, showing inhibition of damage progression by radiography is still a pivotal outcome for the classification of a drug as a DMARD, since radiographs can depict bony and cartilage damage and have proven sensitivity to change even over short-term intervals and at very low levels of overall progression in a population.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJydXluZXN0ZXluPC9BdXRob3I+PFllYXI+MjAwNDwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJydXluZXN0ZXluPC9BdXRob3I+PFllYXI+MjAwNDwvWWVh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ADDIN EN.CITE.DATA 29;30 Rapid attainment of the targeted endpoint is now critical, and to achieve the treatment goal of remission or at least low disease activity within the time frame of 6 months, at least 50% clinical improvement within 3 months is desirable. ADDIN REFMGR.CITE <Refman><Cite><Author>Aletaha</Author><Year>2015</Year><RecNum>2903</RecNum><IDText>Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-month time point</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2903</Ref_ID><Title_Primary>Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-month time point</Title_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>Alasti,F.</Authors_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Date_Primary>2015/9/29</Date_Primary><Keywords>analysis</Keywords><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>Disease</Keywords><Keywords>methods</Keywords><Keywords>Patients</Keywords><Keywords>Rheumatology</Keywords><Keywords>Time</Keywords><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis</Periodical><Misc_3>annrheumdis-2015-208324 [pii];10.1136/annrheumdis-2015-208324 [doi]</Misc_3><Address>Division of Rheumatology, Medical University Vienna, Vienna, Austria
Division of Rheumatology, Medical University Vienna, Vienna, Austria
Division of Rheumatology, Medical University Vienna, Vienna, Austria Second Department of Medicine, Hietzing Hospital, Vienna, Austria</Address><Web_URL>PM:26420577</Web_URL><ZZ_JournalFull><f name="System">Ann Rheum Dis</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>31With rising standards of care and -outcomes, RA management has become increasingly complex over the last decade. Despite the availability of many efficacious agents, treatment strategies that have been developed, and outcomes assessments that have come under scrutiny, the high costs of novel therapies have limited the widespread use of these therapeutic options which may have contributed to inequity. Therefore management recommendations on the approach to treating patients with RA have become increasingly useful in providing physicians, patients, payers, regulators and other health care suppliers with evidence-based guidance supported by the views of experts involved in many of these novel developments. Indeed, EULAR has recently updated the standardized operating procedures on the development of recommendations accounting for the assessment of evidence, expert opinion and inclusion of cost aspects.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MjAxNTwv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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MjAxNTwv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ADDIN EN.CITE.DATA 32 EULAR developed a first set of recommendations for the management of RA with DMARDs in 2010 and updated them in 2013. They were originally based on the evidence provided by five (2010) and three (2013)PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbWlybzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbWlybzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 33-35 systematic literature reviews (SLRs). The EULAR recommendations have been widely used. They have been referred to by national rheumatology societies and regional leagues to inform the development of their own recommendations (such as Canadian, French, German, Mexican, APLAR, PANLAR), as well as by regulatory authorities.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNhcmRpZWw8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNhcmRpZWw8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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==
ADDIN EN.CITE.DATA 36-42 Consistent with our approach to providing evidence-based recommendations, we have continued to evaluate the literature on clinical trials of new agents, new information on established drugs, new strategic trials, new perceptions on outcomes assessments and new insights related to the research agendaPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 16 over the last three years. An abundance of new information motivated us to now further update the EULAR recommendations for the management of RA with DMARDs. MethodsAfter approval by the EULAR Executive Committee, the Convenor (JS) and methodologist (RL) invited a Steering Committee and a Task Force to work on this update of the EULAR recommendations for the management of RA. The 2010 recommendations and their 2013 update adhered to the original EULAR standardized operating procedures for the development of recommendations; ADDIN REFMGR.CITE <Refman><Cite><Author>Dougados</Author><Year>2004</Year><RecNum>1510</RecNum><IDText>EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>1510</Ref_ID><Title_Primary>EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees</Title_Primary><Authors_Primary>Dougados,M.</Authors_Primary><Authors_Primary>Betteridge,N.</Authors_Primary><Authors_Primary>Burmester,G.R.</Authors_Primary><Authors_Primary>Euller-Ziegler,L.</Authors_Primary><Authors_Primary>Guillemin,F.</Authors_Primary><Authors_Primary>Hirvonen,J.</Authors_Primary><Authors_Primary>Lloyd,J.</Authors_Primary><Authors_Primary>Ozen,S.</Authors_Primary><Authors_Primary>da Silva,J.A.</Authors_Primary><Authors_Primary>Emery,P.</Authors_Primary><Authors_Primary>Kalden,J.R.</Authors_Primary><Authors_Primary>Kvien,T.</Authors_Primary><Authors_Primary>Matucci-Cerinic,M.</Authors_Primary><Authors_Primary>Smolen,J.</Authors_Primary><Date_Primary>2004/9</Date_Primary><Keywords>diagnosis</Keywords><Keywords>Europe</Keywords><Keywords>Evidence-Based Medicine</Keywords><Keywords>Humans</Keywords><Keywords>International Cooperation</Keywords><Keywords>methods</Keywords><Keywords>Practice Guidelines as Topic</Keywords><Keywords>Research Design</Keywords><Keywords>Rheumatic Diseases</Keywords><Keywords>standards</Keywords><Keywords>therapy</Keywords><Reprint>Not in File</Reprint><Start_Page>1172</Start_Page><End_Page>1176</End_Page><Periodical>Ann.Rheum Dis.</Periodical><Volume>63</Volume><Issue>9</Issue><Address>Clinique de Rhumatologie B Groupe, Hospitalier Cochin, Paris, France. maxime.dougados@cch.ap-hop-paris.fr</Address><Web_URL>PM:15308532</Web_URL><ZZ_JournalStdAbbrev><f name="System">Ann.Rheum Dis.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>43 the 2016 update followed the recently amended version of these standards,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MjAxNTwv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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MjAxNTwv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ADDIN EN.CITE.DATA 32 which also suggest adherence to the Appraisal of Guidelines for Research & Evaluation (AGREE) recommendations in its updated version (AGREE II). ADDIN REFMGR.CITE <Refman><Cite><Author>Brouwers</Author><Year>2010</Year><RecNum>2390</RecNum><IDText>AGREE II: advancing guideline development, reporting and evaluation in health care</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2390</Ref_ID><Title_Primary>AGREE II: advancing guideline development, reporting and evaluation in health care</Title_Primary><Authors_Primary>Brouwers,M.C.</Authors_Primary><Authors_Primary>Kho,M.E.</Authors_Primary><Authors_Primary>Browman,G.P.</Authors_Primary><Authors_Primary>Burgers,J.S.</Authors_Primary><Authors_Primary>Cluzeau,F.</Authors_Primary><Authors_Primary>Feder,G.</Authors_Primary><Authors_Primary>Fervers,B.</Authors_Primary><Authors_Primary>Graham,I.D.</Authors_Primary><Authors_Primary>Grimshaw,J.</Authors_Primary><Authors_Primary>Hanna,S.E.</Authors_Primary><Authors_Primary>Littlejohns,P.</Authors_Primary><Authors_Primary>Makarski,J.</Authors_Primary><Authors_Primary>Zitzelsberger,L.</Authors_Primary><Date_Primary>2010/12/14</Date_Primary><Keywords>Canada</Keywords><Keywords>Delivery of Health Care</Keywords><Keywords>Health</Keywords><Keywords>Humans</Keywords><Keywords>Manuals as Topic</Keywords><Keywords>methods</Keywords><Keywords>Practice Guidelines as Topic</Keywords><Keywords>Program Development</Keywords><Keywords>Research</Keywords><Keywords>standards</Keywords><Reprint>Not in File</Reprint><Start_Page>E839</Start_Page><End_Page>E842</End_Page><Periodical>CMAJ.</Periodical><Volume>182</Volume><Issue>18</Issue><User_Def_5>PMC3001530</User_Def_5><Misc_3>cmaj.090449 [pii];10.1503/cmaj.090449 [doi]</Misc_3><Address>McMaster University, Hamilton, Ont., Canada. mbrouwer@mcmaster.ca</Address><Web_URL>PM:20603348</Web_URL><ZZ_JournalStdAbbrev><f name="System">CMAJ.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>44 Steering CommitteeThe Steering Committee included 7 rheumatologists, 1 patient representative and 3 fellows. This group initially developed the research questions for the 3 SLRs (SLRs). These SLRs focused on (i) efficacy of sDMARDs (as monotherapy or combination therapy, including both csDMARDs and tsDMARDs) and glucocorticoids; (ii) efficacy of bDMARDs (as monotherapy or combined with csDMARDs); and (iii) safety aspects of sDMARDs and bDMARDs. To this end, the original SLRs obtained in 2013PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbWlybzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbWlybzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 33-35 served as a starting point and an update on the literature published between 2013 and 2016 was performed. New information on treatment strategies was also evaluated in the present SLRs. Formal economic analyses were not performed, but cost aspects were considered throughout the process in line with the current state of the art of developing recommendations.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkd1eWF0dDwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkd1eWF0dDwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl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ADDIN EN.CITE.DATA 45;46 The three rheumatology fellows (KC, JN, SR) performed the SLRs (and checked each other’s work) exploiting existing publication databases on randomized controlled trials for efficacy and registry data for safety, and also evaluating recent EULAR and ACR congress abstracts. Summary-of-Findings (SOF) tables were generated and levels of evidence (LoE) were determined using the standards of the Oxford Centre for Evidence Based Medicine. ADDIN REFMGR.CITE <Refman><Cite><Author>OCEBM Levels of Evidence Working Group</Author><Year>2011</Year><RecNum>2238</RecNum><IDText>The Oxford 2011 Levels of Evidence</IDText><MDL Ref_Type="Grant"><Ref_Type>Grant</Ref_Type><Ref_ID>2238</Ref_ID><Title_Primary><f name="Verdana">The Oxford 2011 Levels of Evidence</f></Title_Primary><Authors_Primary>OCEBM Levels of Evidence Working Group</Authors_Primary><Authors_Primary>Oxford Centre for Evidence-Based Medicine.</Authors_Primary><Date_Primary>2011</Date_Primary><Reprint>Not in File</Reprint><Web_URL_Link3><f name="Verdana"><u> The three SLRs informing the Task Force and a detailed description of their methods are published separately. ADDIN REFMGR.CITE <Refman><Cite><Author>Ramiro S</Author><Year>2016</Year><RecNum>3139</RecNum><IDText>SLR on safety aspects of DMARDs to inform the EULAR RA management task force</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3139</Ref_ID><Title_Primary>SLR on safety aspects of DMARDs to inform the EULAR RA management task force</Title_Primary><Authors_Primary>Ramiro S</Authors_Primary><Authors_Primary>et al</Authors_Primary><Date_Primary>2016</Date_Primary><Keywords>Safety</Keywords><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Nam J</Author><Year>2016</Year><RecNum>3137</RecNum><IDText>SLR on bDMARDs to inform the EULAR RA management task force.</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3137</Ref_ID><Title_Primary>SLR on bDMARDs to inform the EULAR RA management task force.</Title_Primary><Authors_Primary>Nam J</Authors_Primary><Authors_Primary>et al</Authors_Primary><Date_Primary>2016</Date_Primary><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Chatzidionysiou K</Author><Year>2016</Year><RecNum>3138</RecNum><IDText>SLR on csDMARDs to inform the EULAR RA management task force 2016</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3138</Ref_ID><Title_Primary>SLR on csDMARDs to inform the EULAR RA management task force 2016</Title_Primary><Authors_Primary>Chatzidionysiou K</Authors_Primary><Date_Primary>2016</Date_Primary><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>48-50The SoFs of the SLRs were presented to the Steering Committee that formulated a proposal for an update of the recommendations based on this information. The SLR data and the proposals of the Steering Committee were subsequently presented to the whole Task Force for further discussions and ultimately development of the updated recommendations.Task ForceThe Task Force consisted of 50 individuals, including the Steering Committee members. Among the Task Force members were 3 patients, 2 health professionals and 2 delegates of the EULAR young rheumatologists’ network EMEUNET. The rheumatologists were all experienced in the treatment of RA and most had frequently participated in clinical trials; moreover, several of them had experience in patient registries of their countries or in various aspects of outcomes research. The patients and health professionals all had experience in consensus finding activities, as well as most of the rheumatologists. Since we also wished the Task Force’s work to be informed by rheumatologists from other regions of the world, aside from a broad representation from 14 European countries, 2 colleagues from Asia, 1 from Australia, 2 from Latin America and 2 from North America were invited to participate. Several of them had actively participated in developing documents of their regional leagues and/or national societies. All Task Force members declared their potential conflicts of interest before the start of the process. The Task Force agreed upon a few principal considerations upfront. Firstly, all recommendations needed to be discussed in the context of new evidence; where no new evidence was available, the former evidence base was followed. Secondly, any of the previous recommendations (4 overarching principles and 14 recommendations) could be maintained since they had been presented in the 2013 version, amended, shifted in sequence or deleted. Thirdly, drugs that were not (yet) approved in Europe but used elsewhere in the world, or drugs that had not yet undergone regulatory assessment but for which evidence from clinical trials was available, could be considered in recommendations to allow for some anticipation of a potential uptake in clinical practice, with all respective caveats. Finally, there was agreement that all recommendations of 2013, which were either further supported by new evidence or lacked novel information, should be incorporated as previously worded, unless certain components were now considered inappropriate. After the presentation of the SLR results and the Steering Committee’s proposals for the amendment of the recommendations, the Task Force was split into 4 breakout groups. One group reviewed bDMARDs, the second group csDMARDs, the third tsDMARDs, and the fourth glucocorticoids; all groups proposed draft language for respective recommendations to the whole Task Force. Safety aspects were addressed in each of these breakout groups. Consensus FindingRepresentatives of each breakout group reported the results of the respective deliberations and presented proposals for the wording of individual recommendations to the whole Task Force. Thereafter the voting process took place. For an overarching principle or recommendation to be accepted for the final document without further change, a majority of 75% of the votes was required in the first ballot. If this result was not achieved, the respective text was amended and subjected to a second ballot, for which a 67% majority was required. If this ballot was not successful, further textual changes were proposed until a ≥50% majority was attained. The recommendations are presented as finally voted upon. The results of the respective last ballot are presented as percentage of voting members. Notes captured the contents of the discussions and the reasoning behind each decision to be presented in the comments accompanying the individual items. For various reasons, not every Task Force member was present in the room throughout the whole meeting and, therefore, there were slight variations in the numbers of votes. However, at every point in time more than 90% of the members participated in the ballots. After the face-to-face meeting, the recommendations, as agreed by the Task Force, were subjected to an anonymous vote (by e-mail) on the levels of agreement (LoA). Each recommendation received an adjudication on a scale of 0-10, 0 meaning no agreement whatsoever and 10 absolute agreement. During this process, several weeks after the meeting, one individual withdrew from the Task Force, because of views on a particular aspect that had not found a majority during the preceding voting process. This colleague had been present and voted throughout the face-to-face meeting and the respective votes regarding all recommendations are accounted for accordingly, but ultimately the person declined authorship and no vote was cast on the level of agreement. ResultsGeneral aspectsAs before, the 2016 update of the EULAR RA management recommendations reflects the balance of clinical, functional and structural efficacy, safety, costs and patients’ perceptions as perceived by the Task Force. Aspect of drug-toxicity were considered in the overall wording of the recommendations, but data are presented only in the Safety SLR because it is assumed that prescribers are aware of the safety information provided in the manufacturers’ package inserts of the various agents. Also, EULAR has developed a series of documents dealing with safety aspects of RA drugs,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlBldGVyczwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlBldGVyczwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl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ADDIN EN.CITE.DATA 51-56 and various other publications have addressed these aspects.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZ1cnN0PC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZ1cnN0PC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 57-60 In particular, as also suggested by the safety SLR, ADDIN REFMGR.CITE <Refman><Cite><Author>Ramiro S</Author><Year>2016</Year><RecNum>3139</RecNum><IDText>SLR on safety aspects of DMARDs to inform the EULAR RA management task force</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3139</Ref_ID><Title_Primary>SLR on safety aspects of DMARDs to inform the EULAR RA management task force</Title_Primary><Authors_Primary>Ramiro S</Authors_Primary><Authors_Primary>et al</Authors_Primary><Date_Primary>2016</Date_Primary><Keywords>Safety</Keywords><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>48 the major risk of bDMARDs (and also tsDMARDs) is related to infections, and recommendations for vaccinationPFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBBc3NlbiBTLjwvQXV0aG9yPjxZZWFyPjIwMTE8L1ll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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBBc3NlbiBTLjwvQXV0aG9yPjxZZWFyPjIwMTE8L1ll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ADDIN EN.CITE.DATA 54 as well as a score allowing to calculate the risk of infection in patients exposed to bDMARDs have been recently developed.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmFuZ2ZlbGQ8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmFuZ2ZlbGQ8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN EN.CITE.DATA 61;62 Nevertheless, when toxicity constitutes a major issue, a specific warning is provided within the respective recommendation or the accompanying comments. Of note, the 3 SLRs as well as the text accompanying each item should have to be regarded as part and parcel of the recommendation. The individual bullet points represent abbreviated conclusions from the discussions and, as such, do not capture all aspects related to a particular theme; rather, such aspects are elucidated in more detail in the respective explanatory part of the Results section. When classifying DMARDs, the Task Force adhered to the previously used nomenclaturePFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 12;16 as shown in Table 1. This Table also provides a glossary for terms employed in the recommendations. The Task Force did not distinguish between early and established RA, but rather discerned phases of the treatment process by differentiating between patients who are na?ve to any DMARD therapy, patients who had an insufficient response (IR) to initial course(s) of csDMARDs and those who had an IR to bDMARDs. There is currently no evidence for differential responses solely based on disease duration, when leaving differences in baseline damage due to delayed treatment initiation aside. Indeed, trials on MTX-na?ve RA patients used different disease durations for inclusion, which ranged from a few months to several years, without appreciable differences in outcomes upon indirect comparison.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0IENsYWlyIEUuVy48L0F1dGhvcj48WWVhcj4yMDA0PC9Z
ZWFyPjxSZWNOdW0+NzEzPC9SZWNOdW0+PElEVGV4dD5Db21iaW5hdGlvbiBvZiBpbmZsaXhpbWFi
IGFuZCBtZXRob3RyZXhhdGUgdGhlcmFweSBmb3IgZWFybHkgcmhldW1hdG9pZCBhcnRocml0aXM6
IGEgcmFuZG9taXplZCwgY29udHJvbGxlZCB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9Ikpv
dXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjcxMzwvUmVmX0lEPjxU
aXRsZV9QcmltYXJ5PkNvbWJpbmF0aW9uIG9mIGluZmxpeGltYWIgYW5kIG1ldGhvdHJleGF0ZSB0
aGVyYXB5IGZvciBlYXJseSByaGV1bWF0b2lkIGFydGhyaXRpczogYSByYW5kb21pemVkLCBjb250
cm9sbGVkIHRyaWFsPC9UaXRsZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3QgQ2xhaXIgRS5X
LjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIGRlciBIZWlqZGUgRE08L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNtb2xlbiBKUzwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+TWFpbmkgUk48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkJhdGhvbiBKTTwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RW1lcnkgUDwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2V5c3RvbmUgRTwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+U2NoaWZmIE08L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkthbGRlbiBKUjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V2FuZyBC
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EZVdvb2R5IEs8L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PldlaXNzIFI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkJha2VyIEQ8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFjdGl2ZSBD
b250cm9sbGVkIFN0dWR5IG9mIFBhdGllbnRzIFJlY2VpdmluZyBJbmZsaXhpbWFiIGZvciB0aGUg
VHJlYXRtZW50IG9mIFJoZXVtYXRvaWQgQXJ0aHJpdGlzIG9mIEVhcmx5IE9uc2V0IFN0dWR5IEdy
b3VwPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDA0PC9EYXRlX1ByaW1hcnk+PEtl
eXdvcmRzPk1ldGhvdHJleGF0ZTwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcHk8L0tleXdvcmRz
PjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXBy
aW50PjxTdGFydF9QYWdlPjM0MzI8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjM0NDM8L0VuZF9QYWdl
PjxQZXJpb2RpY2FsPkFydGhyaXRpcyBSaGV1bTwvUGVyaW9kaWNhbD48Vm9sdW1lPjUwPC9Wb2x1
bWU+PFpaX0pvdXJuYWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+QXJ0aHJpdGlzIFJoZXVtPC9mPjwv
WlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0Np
dGU+PENpdGU+PEF1dGhvcj5LbGFyZXNrb2cgTDwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl
Y051bT41NjM8L1JlY051bT48SURUZXh0PlRoZXJhcGV1dGljIGVmZmVjdCBvZiB0aGUgY29tYmlu
YXRpb24gb2YgZXRhbmVyY2VwdCBhbmQgbWV0aG90cmV4YXRlIGNvbXBhcmVkIHdpdGggZWFjaCB0
cmVhdG1lbnQgYWxvbmUgaW4gcGF0aWVudHMgd2l0aCByaGV1bWF0b2lkIGFydGhyaXRpczogZG91
YmxlLWJsaW5kIHJhbmRvbWlzZWQgY29udHJvbGxlZCB0cmlhbC48L0lEVGV4dD48TURMIFJlZl9U
eXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5cGU+PFJlZl9JRD41NjM8L1Jl
Zl9JRD48VGl0bGVfUHJpbWFyeT5UaGVyYXBldXRpYyBlZmZlY3Qgb2YgdGhlIGNvbWJpbmF0aW9u
IG9mIGV0YW5lcmNlcHQgYW5kIG1ldGhvdHJleGF0ZSBjb21wYXJlZCB3aXRoIGVhY2ggdHJlYXRt
ZW50IGFsb25lIGluIHBhdGllbnRzIHdpdGggcmhldW1hdG9pZCBhcnRocml0aXM6IGRvdWJsZS1i
bGluZCByYW5kb21pc2VkIGNvbnRyb2xsZWQgdHJpYWwuPC9UaXRsZV9QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+S2xhcmVza29nIEw8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZh
biBkZXIgSGVpamRlIEQ8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlIEphZ2Vy
IEpQPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Hb3VnaCBBLEthbGRlbiBKPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NYWxhaXNlIE08L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5Pk1hcnRpbi1Nb2xhIEU8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PlBhdmVsa2EgSzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2Fu
eSBKPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TZXR0YXMgTDwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V2FqZHVsYSBKPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5QZWRlcnNlbiBSPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5G
ZXRlbmVqYWQgUzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2FuZGEgTTwvQXV0
aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwNDwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5N
ZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+U2FmZXR5PC9LZXl3b3Jkcz48S2V5d29y
ZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48
U3RhcnRfUGFnZT42NzU8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjY4MTwvRW5kX1BhZ2U+PFBlcmlv
ZGljYWw+TGFuY2V0PC9QZXJpb2RpY2FsPjxWb2x1bWU+MzYzPC9Wb2x1bWU+PFpaX0pvdXJuYWxG
dWxsPjxmIG5hbWU9IlN5c3RlbSI+TGFuY2V0PC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtm
b3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5CcmVlZHZl
bGQgRkM8L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxSZWNOdW0+ODA1PC9SZWNOdW0+PElEVGV4
dD5UaGUgUFJFTUlFUiBzdHVkeSAtIEEgbXVsdGljZW50ZXIsIHJhbmRvbWl6ZWQsIGRvdWJsZS1i
bGluZCBjbGluaWNhbCB0cmlhbCBvZiBjb21iaW5hdGlvbiB0aGVyYXB5IHdpdGggYWRhbGltdW1h
YiBwbHVzIG1ldGhvdHJleGF0ZSB2ZXJzdXMgbWV0aG90cmV4YXRlIGFsb25lIG9yIGFkYWxpbXVt
YWIgYWxvbmUgaW4gcGF0aWVudHMgd2l0aCBlYXJseSwgYWdncmVzc2l2ZSByaGV1bWF0b2lkIGFy
dGhyaXRpcyB3aG8gaGFkIG5vdCBoYWQgcHJldmlvdXMgbWV0aG90cmV4YXRlIHRyZWF0bWVudC48
L0lEVGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5
cGU+PFJlZl9JRD44MDU8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5UaGUgUFJFTUlFUiBzdHVkeSAt
IEEgbXVsdGljZW50ZXIsIHJhbmRvbWl6ZWQsIGRvdWJsZS1ibGluZCBjbGluaWNhbCB0cmlhbCBv
ZiBjb21iaW5hdGlvbiB0aGVyYXB5IHdpdGggYWRhbGltdW1hYiBwbHVzIG1ldGhvdHJleGF0ZSB2
ZXJzdXMgbWV0aG90cmV4YXRlIGFsb25lIG9yIGFkYWxpbXVtYWIgYWxvbmUgaW4gcGF0aWVudHMg
d2l0aCBlYXJseSwgYWdncmVzc2l2ZSByaGV1bWF0b2lkIGFydGhyaXRpcyB3aG8gaGFkIG5vdCBo
YWQgcHJldmlvdXMgbWV0aG90cmV4YXRlIHRyZWF0bWVudC48L1RpdGxlX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5CcmVlZHZlbGQgRkM8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PldlaXNtYW4gTUg8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkthdmFuYXVnaCBB
RjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q29oZW4gU0I8L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PlBhdmVsa2EgSzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+dmFuIFZvbGxlbmhvdmVuIFI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PlNoYXJwIEpMPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5QZXJleiBKTDwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3BlbmNlci1HcmVlbiBHVDwvQXV0aG9y
c19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwNjwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5BcnRo
cml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3b3Jk
cz50aGVyYXB5PC9LZXl3b3Jkcz48UmVwcmludD5JbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdl
PjI2PC9TdGFydF9QYWdlPjxFbmRfUGFnZT4zNzwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QXJ0aHJp
dGlzIFJoZXVtPC9QZXJpb2RpY2FsPjxWb2x1bWU+NTQ8L1ZvbHVtZT48WlpfSm91cm5hbEZ1bGw+
PGYgbmFtZT0iU3lzdGVtIj5BcnRocml0aXMgUmhldW08L2Y+PC9aWl9Kb3VybmFsRnVsbD48Wlpf
V29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlNt
b2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051bT4yNzM3PC9SZWNOdW0+PElEVGV4
dD5BZGp1c3RtZW50IG9mIHRoZXJhcHkgaW4gcmhldW1hdG9pZCBhcnRocml0aXMgb24gdGhlIGJh
c2lzIG9mIGFjaGlldmVtZW50IG9mIHN0YWJsZSBsb3cgZGlzZWFzZSBhY3Rpdml0eSB3aXRoIGFk
YWxpbXVtYWIgcGx1cyBtZXRob3RyZXhhdGUgb3IgbWV0aG90cmV4YXRlIGFsb25lOiB0aGUgcmFu
ZG9taXNlZCBjb250cm9sbGVkIE9QVElNQSB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9Ikpv
dXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjI3Mzc8L1JlZl9JRD48
VGl0bGVfUHJpbWFyeT5BZGp1c3RtZW50IG9mIHRoZXJhcHkgaW4gcmhldW1hdG9pZCBhcnRocml0
aXMgb24gdGhlIGJhc2lzIG9mIGFjaGlldmVtZW50IG9mIHN0YWJsZSBsb3cgZGlzZWFzZSBhY3Rp
dml0eSB3aXRoIGFkYWxpbXVtYWIgcGx1cyBtZXRob3RyZXhhdGUgb3IgbWV0aG90cmV4YXRlIGFs
b25lOiB0aGUgcmFuZG9taXNlZCBjb250cm9sbGVkIE9QVElNQSB0cmlhbDwvVGl0bGVfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlNtb2xlbixKLlMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5FbWVyeSxQLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RmxlaXNj
aG1hbm4sUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbiBWb2xsZW5ob3Zl
bixSLkYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5QYXZlbGthLEsuPC9BdXRo
b3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EdXJleixQLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+R3VlcmV0dGUsQi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5Pkt1cHBlcixILjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UmVkZGVuLEwu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Bcm9yYSxWLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+S2F2YW5hdWdoLEEuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVf
UHJpbWFyeT4yMDE0LzEvMjU8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QWR1bHQ8L0tleXdvcmRz
PjxLZXl3b3Jkcz5hZHZlcnNlIGVmZmVjdHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BZ2VkPC9LZXl3
b3Jkcz48S2V5d29yZHM+QW50aWJvZGllczwvS2V5d29yZHM+PEtleXdvcmRzPkFudGlib2RpZXMs
TW9ub2Nsb25hbCxIdW1hbml6ZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5BbnRpcmhldW1hdGljIEFn
ZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkFy
dGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+QXVzdHJpYTwvS2V5d29yZHM+
PEtleXdvcmRzPkJpb2xvZ2ljYWwgQWdlbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+QmlvbWVkaWNh
bCBSZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVhY3RpdmUgUHJvdGVpbjwvS2V5d29y
ZHM+PEtleXdvcmRzPkNhbGlmb3JuaWE8L0tleXdvcmRzPjxLZXl3b3Jkcz5EaXNlYXNlPC9LZXl3
b3Jkcz48S2V5d29yZHM+RG91YmxlLUJsaW5kIE1ldGhvZDwvS2V5d29yZHM+PEtleXdvcmRzPkRy
dWcgQWRtaW5pc3RyYXRpb24gU2NoZWR1bGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJh
cHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5EcnVnIFRoZXJhcHksQ29tYmluYXRpb248L0tleXdvcmRz
PjxLZXl3b3Jkcz5GZW1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5HZXJtYW55PC9LZXl3b3Jkcz48
S2V5d29yZHM+R2x1Y29jb3J0aWNvaWRzPC9LZXl3b3Jkcz48S2V5d29yZHM+SG9zcGl0YWxzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+aW1tdW5vbG9neTwv
S2V5d29yZHM+PEtleXdvcmRzPk1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9LZXl3
b3Jkcz48S2V5d29yZHM+TWV0aG90cmV4YXRlPC9LZXl3b3Jkcz48S2V5d29yZHM+TWlkZGxlIEFn
ZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5NdWx0aWNlbnRlciBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5
d29yZHM+UGF0aWVudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5yYWRpb2dyYXBoeTwvS2V5d29yZHM+
PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3
b3Jkcz48S2V5d29yZHM+U2V2ZXJpdHkgb2YgSWxsbmVzcyBJbmRleDwvS2V5d29yZHM+PEtleXdv
cmRzPlN3ZWRlbjwvS2V5d29yZHM+PEtleXdvcmRzPlRlYWNoaW5nPC9LZXl3b3Jkcz48S2V5d29y
ZHM+VGV4YXM8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxL
ZXl3b3Jkcz50aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+VHJlYXRtZW50IE91dGNvbWU8L0tl
eXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjMyMTwvU3Rh
cnRfUGFnZT48RW5kX1BhZ2U+MzMyPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5MYW5jZXQ8L1Blcmlv
ZGljYWw+PFZvbHVtZT4zODM8L1ZvbHVtZT48SXNzdWU+OTkxNDwvSXNzdWU+PE1pc2NfMz5TMDE0
MC02NzM2KDEzKTYxNzUxLTEgW3BpaV07MTAuMTAxNi9TMDE0MC02NzM2KDEzKTYxNzUxLTEgW2Rv
aV08L01pc2NfMz48QWRkcmVzcz5EaXZpc2lvbiBvZiBSaGV1bWF0b2xvZ3ksIERlcGFydG1lbnQg
b2YgTWVkaWNpbmUgVGhyZWUsIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEsIFZpZW5uYSwg
QXVzdHJpYTsgU2Vjb25kIERlcGFydG1lbnQgb2YgTWVkaWNpbmUsIEhpZXR6aW5nIEhvc3BpdGFs
LCBWaWVubmEsIEF1c3RyaWEuIEVsZWN0cm9uaWMgYWRkcmVzczogam9zZWYuc21vbGVuQG1lZHVu
aXdpZW4uYWMuYXQmI3hBO0xlZWRzIEluc3RpdHV0ZSBvZiBSaGV1bWF0aWMgYW5kIE11c2N1bG9z
a2VsZXRhbCBNZWRpY2luZSwgVW5pdmVyc2l0eSBvZiBMZWVkcywgQ2hhcGVsIEFsbGVydG9uIEhv
c3BpdGFsLCBMZWVkcywgVUs7IE5JSFIgTGVlZHMgTXVzY3Vsb3NrZWxldGFsIEJpb21lZGljYWwg
UmVzZWFyY2ggVW5pdCwgTGVlZHMgVGVhY2hpbmcgSG9zcGl0YWxzIE5IUyBUcnVzdCwgTGVlZHMs
IFVLJiN4QTtEaXZpc2lvbiBvZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgb2YgVGV4YXMgU291
dGh3ZXN0ZXJuIE1lZGljYWwgQ2VudGVyLCBEYWxsYXMsIFRYLCBVU0EmI3hBO0thcm9saW5za2Eg
VW5pdmVyc2l0eSBIb3NwaXRhbCwgU3RvY2tob2xtLCBTd2VkZW4mI3hBO0luc3RpdHV0ZSBhbmQg
Q2xpbmljIG9mIFJoZXVtYXRvbG9neSwgRmlyc3QgTWVkaWNhbCBGYWN1bHR5LCBDaGFybGVzIFVu
aXZlcnNpdHksIFByYWd1ZSwgQ3plY2ggUmVwdWJsaWMmI3hBO1NlcnZpY2UgZXQgUG9sZSBkZSBS
aHVtYXRvbG9naWUsIENsaW5pcXVlcyBVbml2ZXJzaXRhaXJlcyBTYWludC1MdWMsIEluc3RpdHV0
IGRlIFJlY2hlcmNoZSBFeHBlcmltZW50YWxlIGV0IENsaW5pcXVlLCBVbml2ZXJzaXRlIENhdGhv
bGlxdWUgZGUgTG91dmFpbiwgQnJ1c3NlbHMsIEJlbGdpdW0mI3hBO0FiYlZpZSwgTm9ydGggQ2hp
Y2FnbywgSUwsIFVTQSYjeEE7QWJiVmllIERldXRzY2hsYW5kIEdtYkggYW5kIENvbXBhbnkgS0cs
IEx1ZHdpZ3NoYWZlbiwgR2VybWFueSYjeEE7QWJiVmllLCBOb3J0aCBDaGljYWdvLCBJTCwgVVNB
JiN4QTtBYmJWaWUsIE5vcnRoIENoaWNhZ28sIElMLCBVU0EmI3hBO0RpdmlzaW9uIG9mIFJoZXVt
YXRvbG9neSwgQWxsZXJneSBhbmQgSW1tdW5vbG9neSwgVW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlh
IFNhbiBEaWVnbywgTGEgSm9sbGEsIENBLCBVU0E8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjQxNjg5
NTY8L1dlYl9VUkw+PFpaX0pvdXJuYWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+TGFuY2V0PC9mPjwv
WlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0Np
dGU+PC9SZWZtYW4+
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0IENsYWlyIEUuVy48L0F1dGhvcj48WWVhcj4yMDA0PC9Z
ZWFyPjxSZWNOdW0+NzEzPC9SZWNOdW0+PElEVGV4dD5Db21iaW5hdGlvbiBvZiBpbmZsaXhpbWFi
IGFuZCBtZXRob3RyZXhhdGUgdGhlcmFweSBmb3IgZWFybHkgcmhldW1hdG9pZCBhcnRocml0aXM6
IGEgcmFuZG9taXplZCwgY29udHJvbGxlZCB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9Ikpv
dXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjcxMzwvUmVmX0lEPjxU
aXRsZV9QcmltYXJ5PkNvbWJpbmF0aW9uIG9mIGluZmxpeGltYWIgYW5kIG1ldGhvdHJleGF0ZSB0
aGVyYXB5IGZvciBlYXJseSByaGV1bWF0b2lkIGFydGhyaXRpczogYSByYW5kb21pemVkLCBjb250
cm9sbGVkIHRyaWFsPC9UaXRsZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3QgQ2xhaXIgRS5X
LjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIGRlciBIZWlqZGUgRE08L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNtb2xlbiBKUzwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+TWFpbmkgUk48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkJhdGhvbiBKTTwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RW1lcnkgUDwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2V5c3RvbmUgRTwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+U2NoaWZmIE08L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkthbGRlbiBKUjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V2FuZyBC
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EZVdvb2R5IEs8L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PldlaXNzIFI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkJha2VyIEQ8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFjdGl2ZSBD
b250cm9sbGVkIFN0dWR5IG9mIFBhdGllbnRzIFJlY2VpdmluZyBJbmZsaXhpbWFiIGZvciB0aGUg
VHJlYXRtZW50IG9mIFJoZXVtYXRvaWQgQXJ0aHJpdGlzIG9mIEVhcmx5IE9uc2V0IFN0dWR5IEdy
b3VwPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDA0PC9EYXRlX1ByaW1hcnk+PEtl
eXdvcmRzPk1ldGhvdHJleGF0ZTwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcHk8L0tleXdvcmRz
PjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXBy
aW50PjxTdGFydF9QYWdlPjM0MzI8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjM0NDM8L0VuZF9QYWdl
PjxQZXJpb2RpY2FsPkFydGhyaXRpcyBSaGV1bTwvUGVyaW9kaWNhbD48Vm9sdW1lPjUwPC9Wb2x1
bWU+PFpaX0pvdXJuYWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+QXJ0aHJpdGlzIFJoZXVtPC9mPjwv
WlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0Np
dGU+PENpdGU+PEF1dGhvcj5LbGFyZXNrb2cgTDwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl
Y051bT41NjM8L1JlY051bT48SURUZXh0PlRoZXJhcGV1dGljIGVmZmVjdCBvZiB0aGUgY29tYmlu
YXRpb24gb2YgZXRhbmVyY2VwdCBhbmQgbWV0aG90cmV4YXRlIGNvbXBhcmVkIHdpdGggZWFjaCB0
cmVhdG1lbnQgYWxvbmUgaW4gcGF0aWVudHMgd2l0aCByaGV1bWF0b2lkIGFydGhyaXRpczogZG91
YmxlLWJsaW5kIHJhbmRvbWlzZWQgY29udHJvbGxlZCB0cmlhbC48L0lEVGV4dD48TURMIFJlZl9U
eXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5cGU+PFJlZl9JRD41NjM8L1Jl
Zl9JRD48VGl0bGVfUHJpbWFyeT5UaGVyYXBldXRpYyBlZmZlY3Qgb2YgdGhlIGNvbWJpbmF0aW9u
IG9mIGV0YW5lcmNlcHQgYW5kIG1ldGhvdHJleGF0ZSBjb21wYXJlZCB3aXRoIGVhY2ggdHJlYXRt
ZW50IGFsb25lIGluIHBhdGllbnRzIHdpdGggcmhldW1hdG9pZCBhcnRocml0aXM6IGRvdWJsZS1i
bGluZCByYW5kb21pc2VkIGNvbnRyb2xsZWQgdHJpYWwuPC9UaXRsZV9QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+S2xhcmVza29nIEw8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZh
biBkZXIgSGVpamRlIEQ8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlIEphZ2Vy
IEpQPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Hb3VnaCBBLEthbGRlbiBKPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NYWxhaXNlIE08L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5Pk1hcnRpbi1Nb2xhIEU8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PlBhdmVsa2EgSzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2Fu
eSBKPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TZXR0YXMgTDwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V2FqZHVsYSBKPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5QZWRlcnNlbiBSPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5G
ZXRlbmVqYWQgUzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2FuZGEgTTwvQXV0
aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwNDwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5N
ZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+U2FmZXR5PC9LZXl3b3Jkcz48S2V5d29y
ZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48
U3RhcnRfUGFnZT42NzU8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjY4MTwvRW5kX1BhZ2U+PFBlcmlv
ZGljYWw+TGFuY2V0PC9QZXJpb2RpY2FsPjxWb2x1bWU+MzYzPC9Wb2x1bWU+PFpaX0pvdXJuYWxG
dWxsPjxmIG5hbWU9IlN5c3RlbSI+TGFuY2V0PC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtm
b3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5CcmVlZHZl
bGQgRkM8L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxSZWNOdW0+ODA1PC9SZWNOdW0+PElEVGV4
dD5UaGUgUFJFTUlFUiBzdHVkeSAtIEEgbXVsdGljZW50ZXIsIHJhbmRvbWl6ZWQsIGRvdWJsZS1i
bGluZCBjbGluaWNhbCB0cmlhbCBvZiBjb21iaW5hdGlvbiB0aGVyYXB5IHdpdGggYWRhbGltdW1h
YiBwbHVzIG1ldGhvdHJleGF0ZSB2ZXJzdXMgbWV0aG90cmV4YXRlIGFsb25lIG9yIGFkYWxpbXVt
YWIgYWxvbmUgaW4gcGF0aWVudHMgd2l0aCBlYXJseSwgYWdncmVzc2l2ZSByaGV1bWF0b2lkIGFy
dGhyaXRpcyB3aG8gaGFkIG5vdCBoYWQgcHJldmlvdXMgbWV0aG90cmV4YXRlIHRyZWF0bWVudC48
L0lEVGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5
cGU+PFJlZl9JRD44MDU8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5UaGUgUFJFTUlFUiBzdHVkeSAt
IEEgbXVsdGljZW50ZXIsIHJhbmRvbWl6ZWQsIGRvdWJsZS1ibGluZCBjbGluaWNhbCB0cmlhbCBv
ZiBjb21iaW5hdGlvbiB0aGVyYXB5IHdpdGggYWRhbGltdW1hYiBwbHVzIG1ldGhvdHJleGF0ZSB2
ZXJzdXMgbWV0aG90cmV4YXRlIGFsb25lIG9yIGFkYWxpbXVtYWIgYWxvbmUgaW4gcGF0aWVudHMg
d2l0aCBlYXJseSwgYWdncmVzc2l2ZSByaGV1bWF0b2lkIGFydGhyaXRpcyB3aG8gaGFkIG5vdCBo
YWQgcHJldmlvdXMgbWV0aG90cmV4YXRlIHRyZWF0bWVudC48L1RpdGxlX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5CcmVlZHZlbGQgRkM8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PldlaXNtYW4gTUg8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkthdmFuYXVnaCBB
RjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q29oZW4gU0I8L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PlBhdmVsa2EgSzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+dmFuIFZvbGxlbmhvdmVuIFI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PlNoYXJwIEpMPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5QZXJleiBKTDwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3BlbmNlci1HcmVlbiBHVDwvQXV0aG9y
c19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwNjwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5BcnRo
cml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3b3Jk
cz50aGVyYXB5PC9LZXl3b3Jkcz48UmVwcmludD5JbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdl
PjI2PC9TdGFydF9QYWdlPjxFbmRfUGFnZT4zNzwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QXJ0aHJp
dGlzIFJoZXVtPC9QZXJpb2RpY2FsPjxWb2x1bWU+NTQ8L1ZvbHVtZT48WlpfSm91cm5hbEZ1bGw+
PGYgbmFtZT0iU3lzdGVtIj5BcnRocml0aXMgUmhldW08L2Y+PC9aWl9Kb3VybmFsRnVsbD48Wlpf
V29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPlNt
b2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051bT4yNzM3PC9SZWNOdW0+PElEVGV4
dD5BZGp1c3RtZW50IG9mIHRoZXJhcHkgaW4gcmhldW1hdG9pZCBhcnRocml0aXMgb24gdGhlIGJh
c2lzIG9mIGFjaGlldmVtZW50IG9mIHN0YWJsZSBsb3cgZGlzZWFzZSBhY3Rpdml0eSB3aXRoIGFk
YWxpbXVtYWIgcGx1cyBtZXRob3RyZXhhdGUgb3IgbWV0aG90cmV4YXRlIGFsb25lOiB0aGUgcmFu
ZG9taXNlZCBjb250cm9sbGVkIE9QVElNQSB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9Ikpv
dXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjI3Mzc8L1JlZl9JRD48
VGl0bGVfUHJpbWFyeT5BZGp1c3RtZW50IG9mIHRoZXJhcHkgaW4gcmhldW1hdG9pZCBhcnRocml0
aXMgb24gdGhlIGJhc2lzIG9mIGFjaGlldmVtZW50IG9mIHN0YWJsZSBsb3cgZGlzZWFzZSBhY3Rp
dml0eSB3aXRoIGFkYWxpbXVtYWIgcGx1cyBtZXRob3RyZXhhdGUgb3IgbWV0aG90cmV4YXRlIGFs
b25lOiB0aGUgcmFuZG9taXNlZCBjb250cm9sbGVkIE9QVElNQSB0cmlhbDwvVGl0bGVfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlNtb2xlbixKLlMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5FbWVyeSxQLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RmxlaXNj
aG1hbm4sUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbiBWb2xsZW5ob3Zl
bixSLkYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5QYXZlbGthLEsuPC9BdXRo
b3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EdXJleixQLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+R3VlcmV0dGUsQi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5Pkt1cHBlcixILjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UmVkZGVuLEwu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Bcm9yYSxWLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+S2F2YW5hdWdoLEEuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVf
UHJpbWFyeT4yMDE0LzEvMjU8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QWR1bHQ8L0tleXdvcmRz
PjxLZXl3b3Jkcz5hZHZlcnNlIGVmZmVjdHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BZ2VkPC9LZXl3
b3Jkcz48S2V5d29yZHM+QW50aWJvZGllczwvS2V5d29yZHM+PEtleXdvcmRzPkFudGlib2RpZXMs
TW9ub2Nsb25hbCxIdW1hbml6ZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5BbnRpcmhldW1hdGljIEFn
ZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkFy
dGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+QXVzdHJpYTwvS2V5d29yZHM+
PEtleXdvcmRzPkJpb2xvZ2ljYWwgQWdlbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+QmlvbWVkaWNh
bCBSZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVhY3RpdmUgUHJvdGVpbjwvS2V5d29y
ZHM+PEtleXdvcmRzPkNhbGlmb3JuaWE8L0tleXdvcmRzPjxLZXl3b3Jkcz5EaXNlYXNlPC9LZXl3
b3Jkcz48S2V5d29yZHM+RG91YmxlLUJsaW5kIE1ldGhvZDwvS2V5d29yZHM+PEtleXdvcmRzPkRy
dWcgQWRtaW5pc3RyYXRpb24gU2NoZWR1bGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJh
cHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5EcnVnIFRoZXJhcHksQ29tYmluYXRpb248L0tleXdvcmRz
PjxLZXl3b3Jkcz5GZW1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5HZXJtYW55PC9LZXl3b3Jkcz48
S2V5d29yZHM+R2x1Y29jb3J0aWNvaWRzPC9LZXl3b3Jkcz48S2V5d29yZHM+SG9zcGl0YWxzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+aW1tdW5vbG9neTwv
S2V5d29yZHM+PEtleXdvcmRzPk1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9LZXl3
b3Jkcz48S2V5d29yZHM+TWV0aG90cmV4YXRlPC9LZXl3b3Jkcz48S2V5d29yZHM+TWlkZGxlIEFn
ZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5NdWx0aWNlbnRlciBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5
d29yZHM+UGF0aWVudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5yYWRpb2dyYXBoeTwvS2V5d29yZHM+
PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3
b3Jkcz48S2V5d29yZHM+U2V2ZXJpdHkgb2YgSWxsbmVzcyBJbmRleDwvS2V5d29yZHM+PEtleXdv
cmRzPlN3ZWRlbjwvS2V5d29yZHM+PEtleXdvcmRzPlRlYWNoaW5nPC9LZXl3b3Jkcz48S2V5d29y
ZHM+VGV4YXM8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxL
ZXl3b3Jkcz50aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+VHJlYXRtZW50IE91dGNvbWU8L0tl
eXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjMyMTwvU3Rh
cnRfUGFnZT48RW5kX1BhZ2U+MzMyPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5MYW5jZXQ8L1Blcmlv
ZGljYWw+PFZvbHVtZT4zODM8L1ZvbHVtZT48SXNzdWU+OTkxNDwvSXNzdWU+PE1pc2NfMz5TMDE0
MC02NzM2KDEzKTYxNzUxLTEgW3BpaV07MTAuMTAxNi9TMDE0MC02NzM2KDEzKTYxNzUxLTEgW2Rv
aV08L01pc2NfMz48QWRkcmVzcz5EaXZpc2lvbiBvZiBSaGV1bWF0b2xvZ3ksIERlcGFydG1lbnQg
b2YgTWVkaWNpbmUgVGhyZWUsIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEsIFZpZW5uYSwg
QXVzdHJpYTsgU2Vjb25kIERlcGFydG1lbnQgb2YgTWVkaWNpbmUsIEhpZXR6aW5nIEhvc3BpdGFs
LCBWaWVubmEsIEF1c3RyaWEuIEVsZWN0cm9uaWMgYWRkcmVzczogam9zZWYuc21vbGVuQG1lZHVu
aXdpZW4uYWMuYXQmI3hBO0xlZWRzIEluc3RpdHV0ZSBvZiBSaGV1bWF0aWMgYW5kIE11c2N1bG9z
a2VsZXRhbCBNZWRpY2luZSwgVW5pdmVyc2l0eSBvZiBMZWVkcywgQ2hhcGVsIEFsbGVydG9uIEhv
c3BpdGFsLCBMZWVkcywgVUs7IE5JSFIgTGVlZHMgTXVzY3Vsb3NrZWxldGFsIEJpb21lZGljYWwg
UmVzZWFyY2ggVW5pdCwgTGVlZHMgVGVhY2hpbmcgSG9zcGl0YWxzIE5IUyBUcnVzdCwgTGVlZHMs
IFVLJiN4QTtEaXZpc2lvbiBvZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgb2YgVGV4YXMgU291
dGh3ZXN0ZXJuIE1lZGljYWwgQ2VudGVyLCBEYWxsYXMsIFRYLCBVU0EmI3hBO0thcm9saW5za2Eg
VW5pdmVyc2l0eSBIb3NwaXRhbCwgU3RvY2tob2xtLCBTd2VkZW4mI3hBO0luc3RpdHV0ZSBhbmQg
Q2xpbmljIG9mIFJoZXVtYXRvbG9neSwgRmlyc3QgTWVkaWNhbCBGYWN1bHR5LCBDaGFybGVzIFVu
aXZlcnNpdHksIFByYWd1ZSwgQ3plY2ggUmVwdWJsaWMmI3hBO1NlcnZpY2UgZXQgUG9sZSBkZSBS
aHVtYXRvbG9naWUsIENsaW5pcXVlcyBVbml2ZXJzaXRhaXJlcyBTYWludC1MdWMsIEluc3RpdHV0
IGRlIFJlY2hlcmNoZSBFeHBlcmltZW50YWxlIGV0IENsaW5pcXVlLCBVbml2ZXJzaXRlIENhdGhv
bGlxdWUgZGUgTG91dmFpbiwgQnJ1c3NlbHMsIEJlbGdpdW0mI3hBO0FiYlZpZSwgTm9ydGggQ2hp
Y2FnbywgSUwsIFVTQSYjeEE7QWJiVmllIERldXRzY2hsYW5kIEdtYkggYW5kIENvbXBhbnkgS0cs
IEx1ZHdpZ3NoYWZlbiwgR2VybWFueSYjeEE7QWJiVmllLCBOb3J0aCBDaGljYWdvLCBJTCwgVVNB
JiN4QTtBYmJWaWUsIE5vcnRoIENoaWNhZ28sIElMLCBVU0EmI3hBO0RpdmlzaW9uIG9mIFJoZXVt
YXRvbG9neSwgQWxsZXJneSBhbmQgSW1tdW5vbG9neSwgVW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlh
IFNhbiBEaWVnbywgTGEgSm9sbGEsIENBLCBVU0E8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjQxNjg5
NTY8L1dlYl9VUkw+PFpaX0pvdXJuYWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+TGFuY2V0PC9mPjwv
WlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0Np
dGU+PC9SZWZtYW4+
ADDIN EN.CITE.DATA 63-66 The Task Force also took prognostic factors (Table 1) into account, which have similar predictive power irrespective of disease duration. ADDIN REFMGR.CITE <Refman><Cite><Author>Vastesaeger</Author><Year>2009</Year><RecNum>1526</RecNum><IDText>A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>1526</Ref_ID><Title_Primary>A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis</Title_Primary><Authors_Primary>Vastesaeger,N.</Authors_Primary><Authors_Primary>Xu,S.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>St Clair,E.W.</Authors_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Date_Primary>2009/9</Date_Primary><Keywords>analysis</Keywords><Keywords>Arthritis</Keywords><Keywords>methods</Keywords><Keywords>Netherlands</Keywords><Keywords>Patients</Keywords><Keywords>Probability</Keywords><Keywords>Research</Keywords><Keywords>Risk</Keywords><Keywords>Risk Factors</Keywords><Keywords>therapy</Keywords><Reprint>Not in File</Reprint><Start_Page>1114</Start_Page><End_Page>1121</End_Page><Periodical>Rheumatology.(Oxford)</Periodical><Volume>48</Volume><Issue>9</Issue><Address>Department of Medical Affairs, Centocor BV, Leiden, The Netherlands. nathan.vastesaeger@</Address><Web_URL>PM:19589891</Web_URL><ZZ_JournalStdAbbrev><f name="System">Rheumatology.(Oxford)</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>67 Of note, recommendations for the management of early arthritis, including undifferentiated arthritis, have been recently updated. ADDIN REFMGR.CITE <Refman><Cite><Author>Combe B</Author><Year>2016</Year><RecNum>3092</RecNum><IDText>Update on Early RA management</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3092</Ref_ID><Title_Primary>Update on Early RA management</Title_Primary><Authors_Primary>Combe B</Authors_Primary><Authors_Primary>et al</Authors_Primary><Date_Primary>2016</Date_Primary><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>68 The present recommendations address the management of patients with RA from the time of its diagnosis and not pre-RA or undifferentiated arthritis.Overarching principlesAs in previous versions, the Task Force endorsed the presentation of general principles for the treatment of patients with RA as overarching (Table 2). Their nature is so generic that there was no requirement to base them on specific searches or levels of evidence, but at the same time the group believed it is crucial to communicate them as a foundation on which the actual recommendations were based. However, while all three former overarching principles were maintained as formulated in 2010, the Task Force added a 4th one as overarching principle B.Treatment of RA patients should aim at the best care and must be based on a shared decision between the patient and the rheumatologist. This principle remained unchanged both in its textual details and in its place as item A, a prominent position within the recommendations. Shared decision-making between patient and rheumatologist involves all aspects of the disease: information on the disease and its risks, the modalities of disease assessment, decisions on the therapeutic target and the potential means to reach the target, the development of a management plan and discussions on the benefits and risks of individual therapies. These aspects have also been detailed in recommendations on standards of care. ADDIN REFMGR.CITE <Refman><Cite><Author>Stoffer</Author><Year>2014</Year><RecNum>2686</RecNum><IDText>Development of patient-centred standards of care for rheumatoid arthritis in Europe: the project</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2686</Ref_ID><Title_Primary>Development of patient-centred standards of care for rheumatoid arthritis in Europe: the project</Title_Primary><Authors_Primary>Stoffer,M.A.</Authors_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>Woolf,A.</Authors_Primary><Authors_Primary>Ambrozic,A.</Authors_Primary><Authors_Primary>Bosworth,A.</Authors_Primary><Authors_Primary>Carmona,L.</Authors_Primary><Authors_Primary>Fialka-Moser,V.</Authors_Primary><Authors_Primary>Loza,E.</Authors_Primary><Authors_Primary>Olejnik,P.</Authors_Primary><Authors_Primary>Petersson,I.F.</Authors_Primary><Authors_Primary>Uhlig,T.</Authors_Primary><Authors_Primary>Stamm,T.A.</Authors_Primary><Date_Primary>2014/8/6</Date_Primary><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>Consensus</Keywords><Keywords>Europe</Keywords><Keywords>European Union</Keywords><Keywords>Exercise</Keywords><Keywords>Health</Keywords><Keywords>methods</Keywords><Keywords>Patients</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>standards</Keywords><Reprint>Not in File</Reprint><Start_Page>902</Start_Page><End_Page>905</End_Page><Periodical>Ann Rheum Dis</Periodical><Volume>73</Volume><Misc_3>annrheumdis-2013-203743 [pii];10.1136/annrheumdis-2013-203743 [doi]</Misc_3><Address>Internal Medicine III, Division of Rheumatology, Medizinische Universitat Wien, Vienna, Austria</Address><Web_URL>PM:23921994</Web_URL><ZZ_JournalFull><f name="System">Ann Rheum Dis</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>69 Naturally, “best care” refers to the recommendations presented here and inherently “shared decision” relates to all individual recommendations. To this end also quality indicators have been developed more recently.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk5hdmFycm8tQ29tcGFuPC9BdXRob3I+PFllYXI+MjAxNTwv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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk5hdmFycm8tQ29tcGFuPC9BdXRob3I+PFllYXI+MjAxNTwv
WWVhcj48UmVjTnVtPjMxMDU8L1JlY051bT48SURUZXh0PlF1YWxpdHkgaW5kaWNhdG9ycyBpbiBy
aGV1bWF0b2lkIGFydGhyaXRpczogcmVzdWx0cyBmcm9tIHRoZSBNRVRFT1IgZGF0YWJhc2U8L0lE
VGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5cGU+
PFJlZl9JRD4zMTA1PC9SZWZfSUQ+PFRpdGxlX1ByaW1hcnk+UXVhbGl0eSBpbmRpY2F0b3JzIGlu
IHJoZXVtYXRvaWQgYXJ0aHJpdGlzOiByZXN1bHRzIGZyb20gdGhlIE1FVEVPUiBkYXRhYmFzZTwv
VGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk5hdmFycm8tQ29tcGFuLFYuPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TbW9sZW4sSi5TLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+SHVpemluZ2EsVC5XLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1By
aW1hcnk+TGFuZGV3ZSxSLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RmVycmFj
Y2lvbGksRy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRhIFNpbHZhLEouQS48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1vb3RzLFIuSi48L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PktheSxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1By
aW1hcnk+dmFuIGRlciBIZWlqZGUsRC48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIw
MTUvOTwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5BZHZpc29yeSBDb21taXR0ZWVzPC9LZXl3b3Jk
cz48S2V5d29yZHM+QWdlZDwvS2V5d29yZHM+PEtleXdvcmRzPkFudGlyaGV1bWF0aWMgQWdlbnRz
PC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJpdGlzPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJp
dGlzLFJoZXVtYXRvaWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5Bc2lhPC9LZXl3b3Jkcz48S2V5d29y
ZHM+QXVzdHJpYTwvS2V5d29yZHM+PEtleXdvcmRzPkF1dG9hbnRpYm9kaWVzPC9LZXl3b3Jkcz48
S2V5d29yZHM+Ymxvb2Q8L0tleXdvcmRzPjxLZXl3b3Jkcz5DaHJvbmljIERpc2Vhc2U8L0tleXdv
cmRzPjxLZXl3b3Jkcz5EYXRhYmFzZXMsRmFjdHVhbDwvS2V5d29yZHM+PEtleXdvcmRzPmRpYWdu
b3NpczwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vhc2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVn
IHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5FdXJvcGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5G
ZWFzaWJpbGl0eSBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5d29yZHM+RmVtYWxlPC9LZXl3b3Jkcz48
S2V5d29yZHM+SG9zcGl0YWxzPC9LZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48
S2V5d29yZHM+aW1tdW5vbG9neTwvS2V5d29yZHM+PEtleXdvcmRzPkludGVybmF0aW9uYWwgQWdl
bmNpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5JdGFseTwvS2V5d29yZHM+PEtleXdvcmRzPk1hbGU8
L0tleXdvcmRzPjxLZXl3b3Jkcz5NYXNzYWNodXNldHRzPC9LZXl3b3Jkcz48S2V5d29yZHM+bWV0
aG9kczwvS2V5d29yZHM+PEtleXdvcmRzPk1pZGRsZSBBZ2VkPC9LZXl3b3Jkcz48S2V5d29yZHM+
TXVsdGljZW50ZXIgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPk5ldGhlcmxhbmRzPC9LZXl3
b3Jkcz48S2V5d29yZHM+Tm9ydGggQW1lcmljYTwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRz
PC9LZXl3b3Jkcz48S2V5d29yZHM+UXVhbGl0eSBBc3N1cmFuY2UsSGVhbHRoIENhcmU8L0tleXdv
cmRzPjxLZXl3b3Jkcz5RdWFsaXR5IEluZGljYXRvcnMsSGVhbHRoIENhcmU8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJldHJvc3BlY3RpdmUgU3R1ZGll
czwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRpYyBEaXNlYXNlczwvS2V5d29yZHM+PEtleXdv
cmRzPlJoZXVtYXRvbG9neTwvS2V5d29yZHM+PEtleXdvcmRzPlNldmVyaXR5IG9mIElsbG5lc3Mg
SW5kZXg8L0tleXdvcmRzPjxLZXl3b3Jkcz5zdGFuZGFyZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz50
aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5UaW1lPC9LZXl3b3Jkcz48S2V5d29y
ZHM+VHJlYXRtZW50IE91dGNvbWU8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXBy
aW50PjxTdGFydF9QYWdlPjE2MzA8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjE2Mzk8L0VuZF9QYWdl
PjxQZXJpb2RpY2FsPlJoZXVtYXRvbG9neS4oT3hmb3JkKTwvUGVyaW9kaWNhbD48Vm9sdW1lPjU0
PC9Wb2x1bWU+PElzc3VlPjk8L0lzc3VlPjxNaXNjXzM+a2V2MTA4IFtwaWldOzEwLjEwOTMvcmhl
dW1hdG9sb2d5L2tldjEwOCBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPkRlcGFydG1lbnQgb2YgUmhl
dW1hdG9sb2d5LCBMZWlkZW4gVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgTGVpZGVuLCBUaGUg
TmV0aGVybGFuZHMsIG12aWN0b3JpYS5uYXZhcnJvY0BnbWFpbC5jb20mI3hBO0RlcGFydG1lbnQg
b2YgSW50ZXJuYWwgTWVkaWNpbmUgSUlJLCBNZWRpY2FsIFVuaXZlcnNpdHkgb2YgVmllbm5hIDJu
ZCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBDZW50ZXIgZm9yIFJoZXVtYXRpYyBEaXNlYXNlcywg
SGlldHppbmcgSG9zcGl0YWwsIFZpZW5uYSwgQXVzdHJpYSYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1
bWF0b2xvZ3ksIExlaWRlbiBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBMZWlkZW4sIFRoZSBO
ZXRoZXJsYW5kcyYjeEE7QW1zdGVyZGFtIFJoZXVtYXRvbG9neSBDZW50ZXIsIEFtc3RlcmRhbSwg
RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIEF0cml1bSBNZWRpY2FsIENlbnRlciBIZWVybGVu
LCBIZWVybGVuLCBUaGUgTmV0aGVybGFuZHMmI3hBO0RpdmlzaW9uIG9mIFJoZXVtYXRvbG9neSwg
SW5zdGl0dXRlIG9mIFJoZXVtYXRvbG9neSBhbmQgQWZmaW5lIFNjaWVuY2VzLCBTY2hvb2wgb2Yg
TWVkaWNpbmUsIENhdGhvbGljIFVuaXZlcnNpdHkgb2YgdGhlIFNhY3JlZCBIZWFydCwgUm9tZSwg
SXRhbHkmI3hBO0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5LCBIb3NwaXRhbHMgYW5kIEZhY3Vs
dHkgb2YgTWVkaWNpbmUsIFVuaXZlcnNpdHkgb2YgQ29pbWJyYSwgUG9ydHVnYWwmI3hBO0luc3Rp
dHV0ZSBmb3IgQ2hyb25pYyBEaXNlYXNlcyBhbmQgQWdlaW5nLCBVbml2ZXJzaXR5IG9mIExpdmVy
cG9vbCwgTGl2ZXJwb29sLCBVSyBhbmQmI3hBO0RpdmlzaW9uIG9mIFJoZXVtYXRvbG9neSwgRGVw
YXJ0bWVudCBvZiBNZWRpY2luZSwgVU1hc3MgTWVtb3JpYWwgTWVkaWNhbCBDZW50ZXIgYW5kIFVu
aXZlcnNpdHkgb2YgTWFzc2FjaHVzZXR0cyBNZWRpY2FsIFNjaG9vbCwgV29yY2VzdGVyLCBNQSwg
VVNBJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgTGVpZGVuIFVuaXZlcnNpdHkgTWVk
aWNhbCBDZW50ZXIsIExlaWRlbiwgVGhlIE5ldGhlcmxhbmRzPC9BZGRyZXNzPjxXZWJfVVJMPlBN
OjI1ODc3OTEwPC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5hbWU9IlN5c3RlbSI+
UmhldW1hdG9sb2d5LihPeGZvcmQpPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48WlpfV29ya2Zv
cm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1hbj5=
ADDIN EN.CITE.DATA 70 Treatment decisions are based on disease activity and other patient factors, such as progression of structural damage, comorbidities and safety issues. This is a new principle. It derives from previous recommendation 14, the last item of the 2013 version, which was deemed by the current Task Force to represent such a central and self-evident rule to any therapeutic approach that it should constitute an overarching principle rather than a recommendation. Indeed, in line with these considerations, the level of evidence of this recommendation had been rather low in 2013. Withdrawing this item from the recommendations elicited some discussions. Especially the patients brought forward that ending the list of recommendations with an item related to patient-related factors would convey prominence to patient preferences and patient aspects in the management of RA. However, the reasoning that this item would even benefit more from being a general principle than a recommendation, which was unlikely to ever be studied in all its subtleties, prevailed to an extent that principle B was unanimously accepted (Table 2).Rheumatologists are the specialists who should primarily care for RA patients. Originally presented as item B, the wording of this principle was not changed. Of interest, in 2010 this was even presented as overarching principle A. However, over the last years it was recognized, that shared decision-making and considerations of patient factors should receive the most prominent recognition. Whether positioned as A, B or C, this item addresses the importance of specialty care for a complex disease like RA. There is compelling evidence that being cared for by a rheumatologist is advantageous for the patients in terms of early initiation of therapy, prevention of damage and reduction in surgical procedures if a rheumatologist cares for them.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPldpZGRpZmllbGQ8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPldpZGRpZmllbGQ8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN EN.CITE.DATA 71-75 Moreover, rheumatologists have the most profound experience regarding the use of csDMARDs and bDMARDs. This includes the adverse event profiles of these drugs, as well as regarding comorbidities in RA. Therefore, rheumatologists can provide the “best care” in accordance with item A, in the sense of a holistic approach. The reasoning behind the term “primarily” has been discussed amply in previous versions of the recommendations and relates to considerations of multidisciplinary care, including specialty nurses, and of the fact that in certain areas of the world Rheumatology training is not sufficiently provided and other experts may have experience in the management of RA. Moreover, some comorbidities, such as chronic hepatitis or interstitial lung disease, may require consultation of, and treatment by, other specialists.RA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist. Again, this principle is worded exactly as last time, except that it was item C, but also last.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl
Y051bT4yNzQyPC9SZWNOdW0+PElEVGV4dD5FVUxBUiByZWNvbW1lbmRhdGlvbnMgZm9yIHRoZSBt
YW5hZ2VtZW50IG9mIHJoZXVtYXRvaWQgYXJ0aHJpdGlzIHdpdGggc3ludGhldGljIGFuZCBiaW9s
b2dpY2FsIGRpc2Vhc2UtbW9kaWZ5aW5nIGFudGlyaGV1bWF0aWMgZHJ1Z3M6IDIwMTMgdXBkYXRl
PC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9U
eXBlPjxSZWZfSUQ+Mjc0MjwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PkVVTEFSIHJlY29tbWVuZGF0
aW9ucyBmb3IgdGhlIG1hbmFnZW1lbnQgb2YgcmhldW1hdG9pZCBhcnRocml0aXMgd2l0aCBzeW50
aGV0aWMgYW5kIGJpb2xvZ2ljYWwgZGlzZWFzZS1tb2RpZnlpbmcgYW50aXJoZXVtYXRpYyBkcnVn
czogMjAxMyB1cGRhdGU8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TbW9sZW4sSi5T
LjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGFuZGV3ZSxSLjwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QnJlZWR2ZWxkLEYuQy48L0F1dGhvcnNfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PkJ1Y2gsTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PkJ1cm1lc3RlcixHLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RG91Z2Fkb3Ms
TS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkVtZXJ5LFAuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HYXVqb3V4LVZpYWxhLEMuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5Hb3NzZWMsTC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5Pk5hbSxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UmFtaXJvLFMuPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5XaW50aHJvcCxLLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+RGUsV2l0IE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5BbGV0YWhhLEQuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5CZXR0
ZXJpZGdlLE4uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5CaWpsc21hLEouVy48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJvZXJzLE0uPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5CdXR0Z2VyZWl0LEYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5Db21iZSxCLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q3V0
b2xvLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EYW1qYW5vdixOLjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF6ZXMsSi5NLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+S291bG91bWFzLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5LdmllbixULksuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NYXJp
ZXR0ZSxYLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UGF2ZWxrYSxLLjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIFJpZWwsUC5MLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+UnViYmVydC1Sb3RoLEEuPC9BdXRob3JzX1ByaW1hcnk+PEF1
dGhvcnNfUHJpbWFyeT5TY2hvbHRlLVZvc2hhYXIsTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PlNjb3R0LEQuTC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNv
a2thLUlzbGVyLFQuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Xb25nLEouQi48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbiBkZXIgSGVpamRlLEQuPC9BdXRo
b3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDE0LzMvMTwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jk
cz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BdXN0cmlhPC9LZXl3b3Jkcz48S2V5d29y
ZHM+Q29uc2Vuc3VzPC9LZXl3b3Jkcz48S2V5d29yZHM+RGVjaXNpb24gTWFraW5nPC9LZXl3b3Jk
cz48S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRzPkdsdWNvY29ydGljb2lkczwv
S2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9s
b2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+UmlzazwvS2V5d29yZHM+PEtleXdvcmRzPlJpc2sgRmFj
dG9yczwvS2V5d29yZHM+PEtleXdvcmRzPlNhZmV0eTwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJh
cHk8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjQ5
MjwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+NTA5PC9FbmRfUGFnZT48UGVyaW9kaWNhbD5Bbm4gUmhl
dW0gRGlzPC9QZXJpb2RpY2FsPjxWb2x1bWU+NzM8L1ZvbHVtZT48SXNzdWU+MzwvSXNzdWU+PE1p
c2NfMz5hbm5yaGV1bWRpcy0yMDEzLTIwNDU3MyBbcGlpXTsxMC4xMTM2L2FubnJoZXVtZGlzLTIw
MTMtMjA0NTczIFtkb2ldPC9NaXNjXzM+PEFkZHJlc3M+RGl2aXNpb24gb2YgUmhldW1hdG9sb2d5
LCBEZXBhcnRtZW50IG9mIE1lZGljaW5lIDMsIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEs
ICwgVmllbm5hLCBBdXN0cmlhPC9BZGRyZXNzPjxXZWJfVVJMPlBNOjI0MTYxODM2PC9XZWJfVVJM
PjxaWl9Kb3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFubiBSaGV1bSBEaXM8L2Y+PC9aWl9K
b3VybmFsRnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48
L1JlZm1hbj4A
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 16 It is meant to remind all stakeholders that effective RA therapy – in spite of its direct costs – will reduce the economic burden on the individual patients, their families and society, which not only includes direct medical costs, but also indirect costs such as work disability and premature retirement. In this context it must be borne in mind that direct medical costs accrue beyond those attributed to directly treating the overt manifestations of RA, but also to include costs ensuing from comorbidities related to the inflammatory process. This point, however, is also meant to echo that cost-effective treatment approaches must be preferred as long as safety and outcomes are similar compared with more costly ones and in line with the therapeutic paradigms. ADDIN REFMGR.CITE <Refman><Cite><Author>Holloway K</Author><Year>2011</Year><RecNum>3046</RecNum><IDText>The World Medicines Situation 2011. Rational Use of Medicines. WHO/EMP/MIE/2011.2.2</IDText><MDL Ref_Type="Book, Whole"><Ref_Type>Book, Whole</Ref_Type><Ref_ID>3046</Ref_ID><Title_Primary>The World Medicines Situation 2011. Rational Use of Medicines. <f name="ShinnMedium">WHO/EMP/MIE/2011.2.2</f></Title_Primary><Authors_Primary>Holloway K</Authors_Primary><Authors_Primary>van Dijk L</Authors_Primary><Date_Primary>2011</Date_Primary><Reprint>Not in File</Reprint><Pub_Place>Geneva</Pub_Place><Publisher>World Health Organzization</Publisher><ZZ_WorkformID>2</ZZ_WorkformID></MDL></Cite></Refman>46 In some countries, the high cost of treatment is an important factor limiting the availability of modern therapies (inequity) , and this factor has to be considered when choosing a treatment strategy. ADDIN REFMGR.CITE <Refman><Cite><Author>Nasonov</Author><Year>2015</Year><RecNum>2858</RecNum><IDText>Does Russia need a treat-to-target initiative?</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2858</Ref_ID><Title_Primary>Does Russia need a treat-to-target initiative?</Title_Primary><Authors_Primary>Nasonov,E.L.</Authors_Primary><Authors_Primary>Karateev,D.E.</Authors_Primary><Date_Primary>2015/3</Date_Primary><Keywords>Arthritis</Keywords><Keywords>Disease</Keywords><Keywords>pathology</Keywords><Keywords>Research</Keywords><Keywords>Rheumatic Diseases</Keywords><Keywords>Rheumatology</Keywords><Reprint>Not in File</Reprint><Start_Page>381</Start_Page><End_Page>382</End_Page><Periodical>Rheumatology.(Oxford)</Periodical><Volume>54</Volume><Issue>3</Issue><Misc_3>keu156 [pii];10.1093/rheumatology/keu156 [doi]</Misc_3><Address>Department of Vascular Pathology of Rheumatic Diseases and Early Arthritis Department, Research Institute of Rheumatology, Russian Academy of Medical Sciences (RAMS), Moscow, Russian Federation
Department of Vascular Pathology of Rheumatic Diseases and Early Arthritis Department, Research Institute of Rheumatology, Russian Academy of Medical Sciences (RAMS), Moscow, Russian Federation. karateev@irramn.ru dekar@inbox.ru</Address><Web_URL>PM:24736164</Web_URL><ZZ_JournalStdAbbrev><f name="System">Rheumatology.(Oxford)</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>76 In this respect, the advent of biosimilars provides potential for reduction of pressure on health care budgets.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRvcm5lcjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRvcm5lcjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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==
ADDIN EN.CITE.DATA 77 At this point it also must be considered that many patients still do not attain the therapeutic targets, despite all of our modern therapies and therapeutic strategies. Furthermore, any of the bDMARDs, if applied after at least one csDMARD and a bDMARD has failed, leads to only about 10% good treatment responses in terms of ACR70 rates. ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen</Author><Year>2015</Year><RecNum>3054</RecNum><IDText>Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3054</Ref_ID><Title_Primary>Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges</Title_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Date_Primary>2015/5</Date_Primary><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Austria</Keywords><Keywords>Biological Factors</Keywords><Keywords>Chronic Disease</Keywords><Keywords>Disease</Keywords><Keywords>Disease Progression</Keywords><Keywords>drug therapy</Keywords><Keywords>history</Keywords><Keywords>Humans</Keywords><Keywords>methods</Keywords><Keywords>Molecular Targeted Therapy</Keywords><Keywords>Patients</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>therapeutic use</Keywords><Keywords>therapy</Keywords><Keywords>Treatment Outcome</Keywords><Reprint>Not in File</Reprint><Start_Page>276</Start_Page><End_Page>289</End_Page><Periodical>Nat.Rev.Rheumatol</Periodical><Volume>11</Volume><Issue>5</Issue><Misc_3>nrrheum.2015.8 [pii];10.1038/nrrheum.2015.8 [doi]</Misc_3><Address>Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria</Address><Web_URL>PM:25687177</Web_URL><ZZ_JournalStdAbbrev><f name="System">Nat.Rev.Rheumatol</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>78 These aspects impose the need to continue the search for new therapies or strategies.Recommendations General aspectsThe Task Force’s deliberative process resulted in 12 recommendations. The reduction by 2 recommendations compared with the past EULAR document may be somewhat surprising given the allegedly increasing intricacy of therapeutic modalities and strategies. However, the content of recommendation 14 was shifted into the overarching principles as discussed above. Moreover, item 11 of the 2013 version, which addressed the use of tofacitinib, was deleted as a separate item, because Janus kinase inhibitors as tsDMARDs have now entered into and expanded other recommendations; this will be discussed in more detail in the context of items 8, 9 and 10. Also former recommendation 6, which addressed the use of csDMARD combinations, was deleted by the Task Force; combination therapy with csDMARDs and the reasons to remove it from its previous prominence within the list of recommendations and the algorithm will be addressed in the discussion on recommendations 4 and 5. While 3 of the 2013 recommendations were deleted via either complete omission or incorporation into other items, former bullet recommendation 8 which addressed the absence or presence of prognostic risk factors was split into new recommendations 7 and 8; a detailed rationale for this decision is discussed below. The 12 recommendations form a logical sequence. They start with the need to initiate effective therapy immediately after diagnosis and the requirement to set a treatment target and to assess the disease on the way toward that target, employing a treat-to-target strategy. Such strategy has been strongly embedded into the recommendations since their first version in 2010. With these prerequisites in mind, different drugs or combinations of agents are recommended in the course of the therapeutic procedures, with suggested sequential increments, taking prognostic factors and all approved agents into account. They also mention some agents of potential future interest, even though not yet approved by international regulatory authorities. Thus, the recommendations also include a prospective view on drugs that have undergone phase 3 trials and were available for evidence assessment; obviously their actual prescription will depend on the regulatory approval status in individual countries. The set of recommendations concludes with suggestions toward reduction of therapy and even withdrawal of some drugs when the desired target has been attained and is sustained. Individual recommendationsTherapy with DMARDs should be started as soon as the diagnosis of RA is made. This recommendation remained unchanged compared with 2013 and is one of the mainstays of any treatment approach to RA. It implies (i) the necessity to establish a diagnosis as early as possible, as has been reflected also in the 2010 ACR-EULAR classification criteria;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGEgRDwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+
PFJlY051bT4xNTcxPC9SZWNOdW0+PElEVGV4dD5UaGUgMjAxMCBBbWVyaWNhbiBDb2xsZWdlIG9m
IFJoZXVtYXRvbG9neSAvIEV1cm9wZWFuIExlYWd1ZSBBZ2FpbnN0IFJoZXVtYXRpc20gQ2xhc3Np
ZmljYXRpb24gQ3JpdGVyaWEgZm9yIFJoZXVtYXRvaWQgQXJ0aHJpdGlzLjwvSURUZXh0PjxNREwg
UmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjE1
NzE8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5UaGUgMjAxMCBBbWVyaWNhbiBDb2xsZWdlIG9mIFJo
ZXVtYXRvbG9neSAvIEV1cm9wZWFuIExlYWd1ZSBBZ2FpbnN0IFJoZXVtYXRpc20gQ2xhc3NpZmlj
YXRpb24gQ3JpdGVyaWEgZm9yIFJoZXVtYXRvaWQgQXJ0aHJpdGlzLjwvVGl0bGVfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PkFsZXRhaGEgRDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1h
cnk+TmVvZ2kgVDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2lsbWFuIEE8L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZ1bm92aXRzIEo8L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PkZlbHNvbiBEPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5CaW5naGFtIENPIElJSTwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QnJp
bmJhdW0gTjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QnVybWVzdGVyIEc8L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJ5a2VyayBWPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5vaGVuIE08L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PkNvbWJlIEI8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkNvc3RlbmJhZGVyIEs8
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkRvdWdhZG9zIE08L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PkVtZXJ5IFA8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkZlcnJhY2lvbGkgRzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF6
ZXMgTTwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SG9iYnMgSzwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SHVpemluZ2EgVDwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+S2F2YW5hdWdoIEE8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PktheSBKPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LdmllbiBUSzwvQXV0aG9y
c19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGFpbmcgVDwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+TWVhc2UgUDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TSYj
eEU5O25hcmQgSEE8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1vcmVsYW5kIEw8
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk5hZGVuIFI8L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlBpbmN1cyBUPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5TbW9sZW4gSlM8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlN0YW5pc2xh
d3NrYS1CaWVybmF0IEU8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlN5bW1vbnMg
RDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+VGFrIFBQPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5VcGNodXJjaCBLPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5WZW5jb3Zza3kgSjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V29s
ZmUgRjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF3a2VyIEc8L0F1dGhvcnNf
UHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTA8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+UmhldW1h
dG9sb2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+Y2xhc3NpZmljYXRpb248L0tleXdvcmRzPjxLZXl3
b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxT
dGFydF9QYWdlPjE1ODA8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjE1ODg8L0VuZF9QYWdlPjxQZXJp
b2RpY2FsPkFubiBSaGV1bSBEaXM8L1BlcmlvZGljYWw+PFZvbHVtZT42OTwvVm9sdW1lPjxaWl9K
b3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFubiBSaGV1bSBEaXM8L2Y+PC9aWl9Kb3VybmFs
RnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1h
bj5=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGEgRDwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+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ADDIN EN.CITE.DATA 14 PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNhZGVyPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNhZGVyPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 79;80 and (ii) the advantage of early initiation of DMARD treatment (“as soon as possible”), which enables prevention of damage in a large proportion of patients.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBBa2VuIEo8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBBa2VuIEo8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFy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ADDIN EN.CITE.DATA 74;81-83 Because of the generic nature of this bullet point, the Task Force did not specify the type of DMARD here. Indeed, all DMARDs enable a better long-term outcome upon early, compared with delayed institution, and the sequence of the types of DMARD therapies is addressed in subsequent recommendations. The Task Force did not deal with pre-RA or undifferentiated arthritis and thus assumed that a diagnosis of RA had already been made. However, it should be borne in mind that any chronic arthritis, even if undifferentiated, requires appropriate treatment, including consideration of DMARD therapy, because it usually does not subside spontaneously,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1hY2hvbGQ8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1hY2hvbGQ8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS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==
ADDIN EN.CITE.DATA 84;85 and an update of the recommendations for management of early arthritis has just been presented by EULAR. ADDIN REFMGR.CITE <Refman><Cite><Author>Combe B</Author><Year>2016</Year><RecNum>3092</RecNum><IDText>Update on Early RA management</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3092</Ref_ID><Title_Primary>Update on Early RA management</Title_Primary><Authors_Primary>Combe B</Authors_Primary><Authors_Primary>et al</Authors_Primary><Date_Primary>2016</Date_Primary><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>68 With a level of agreement of 9.9, this recommendation achieved the highest agreement of all items (Table 2). LoE 1a; LoA 9.9Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient. Communication with the patient to clarify and agree on the treatment goal and the means to attain this goal is of utmost importance. It allows alignment of the patient’s and provider’s considerations and aims and enhances adherence. In 2010, the notion “as soon as possible” was also part of this itemPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl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ADDIN EN.CITE.DATA 86 and in the current discussion it was specifically decided to mention that the treatment target should be rapidly attained rather than aiming to achieve it in a more distant future. Indeed, there is sufficient evidence that most patients who do not attain significant improvement within 3 months, or do not achieve the treatment target within 6 months, will not reach the desired state subsequently;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPktsYXJlbmJlZWs8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPktsYXJlbmJlZWs8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy
PjxSZWNOdW0+MjU3NDwvUmVjTnVtPjxJRFRleHQ+VGhlIGltcGFjdCBvZiBmb3VyIGR5bmFtaWMs
IGdvYWwtc3RlZXJlZCB0cmVhdG1lbnQgc3RyYXRlZ2llcyBvbiB0aGUgNS15ZWFyIG91dGNvbWVz
IG9mIHJoZXVtYXRvaWQgYXJ0aHJpdGlzIHBhdGllbnRzIGluIHRoZSBCZVN0IHN0dWR5PC9JRFRl
eHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxS
ZWZfSUQ+MjU3NDwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PlRoZSBpbXBhY3Qgb2YgZm91ciBkeW5h
bWljLCBnb2FsLXN0ZWVyZWQgdHJlYXRtZW50IHN0cmF0ZWdpZXMgb24gdGhlIDUteWVhciBvdXRj
b21lcyBvZiByaGV1bWF0b2lkIGFydGhyaXRpcyBwYXRpZW50cyBpbiB0aGUgQmVTdCBzdHVkeTwv
VGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PktsYXJlbmJlZWssTi5CLjwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+R3VsZXItWXVrc2VsLE0uPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT52YW4gZGVyIEtvb2lqLFMuTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0
aG9yc19QcmltYXJ5PkhhbixLLkguPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5S
b25kYXksSC5LLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2Vyc3RlbnMsUC5K
LjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U2V5cyxQLkUuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5IdWl6aW5nYSxULlcuPC9BdXRob3JzX1ByaW1hcnk+PEF1
dGhvcnNfUHJpbWFyeT5EaWprbWFucyxCLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5BbGxhYXJ0LEMuRi48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTEvNjwv
RGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5BZHVsdDwvS2V5d29yZHM+PEtleXdvcmRzPmFkdmVyc2Ug
ZWZmZWN0czwvS2V5d29yZHM+PEtleXdvcmRzPkFnZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5hbnRh
Z29uaXN0cyAmYW1wOyBpbmhpYml0b3JzPC9LZXl3b3Jkcz48S2V5d29yZHM+QW50aWJvZGllczwv
S2V5d29yZHM+PEtleXdvcmRzPkFudGlib2RpZXMsTW9ub2Nsb25hbDwvS2V5d29yZHM+PEtleXdv
cmRzPkFudGlyaGV1bWF0aWMgQWdlbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJpdGlzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJpdGlzLFJoZXVtYXRvaWQ8L0tleXdvcmRzPjxLZXl3b3Jk
cz5Db21wYXJhdGl2ZSBTdHVkeTwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vhc2U8L0tleXdvcmRz
PjxLZXl3b3Jkcz5EaXNlYXNlIFByb2dyZXNzaW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+ZHJ1ZyB0
aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+RHJ1ZyBUaGVyYXB5LENvbWJpbmF0aW9uPC9LZXl3
b3Jkcz48S2V5d29yZHM+RmVtYWxlPC9LZXl3b3Jkcz48S2V5d29yZHM+R2x1Y29jb3J0aWNvaWRz
PC9LZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5
d29yZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NZXRob3RyZXhhdGU8
L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwvS2V5d29yZHM+PEtleXdvcmRzPk11bHRp
Y2VudGVyIFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5OZXRoZXJsYW5kczwvS2V5d29yZHM+
PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+UHJlZG5pc29uZTwvS2V5d29y
ZHM+PEtleXdvcmRzPlF1YWxpdHkgb2YgTGlmZTwvS2V5d29yZHM+PEtleXdvcmRzPnJhZGlvZ3Jh
cGh5PC9LZXl3b3Jkcz48S2V5d29yZHM+UmVtaXNzaW9uIEluZHVjdGlvbjwvS2V5d29yZHM+PEtl
eXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jk
cz48S2V5d29yZHM+c2Vjb25kYXJ5PC9LZXl3b3Jkcz48S2V5d29yZHM+U2V2ZXJpdHkgb2YgSWxs
bmVzcyBJbmRleDwvS2V5d29yZHM+PEtleXdvcmRzPlNpbmdsZS1CbGluZCBNZXRob2Q8L0tleXdv
cmRzPjxLZXl3b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5
PC9LZXl3b3Jkcz48S2V5d29yZHM+dG94aWNpdHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5UcmVhdG1l
bnQgT3V0Y29tZTwvS2V5d29yZHM+PEtleXdvcmRzPlR1bW9yIE5lY3Jvc2lzIEZhY3Rvci1hbHBo
YTwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+MTAz
OTwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+MTA0NjwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QW5uIFJo
ZXVtIERpczwvUGVyaW9kaWNhbD48Vm9sdW1lPjcwPC9Wb2x1bWU+PElzc3VlPjY8L0lzc3VlPjxN
aXNjXzM+YXJkLjIwMTAuMTQxMjM0IFtwaWldOzEwLjExMzYvYXJkLjIwMTAuMTQxMjM0IFtkb2ld
PC9NaXNjXzM+PEFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIEMtMDEtUiwgTGVp
ZGVuIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBPIEJveCA5NjAwLCAyMzAwIFJDIExlaWRl
biwgVGhlIE5ldGhlcmxhbmRzLiBuLmIua2xhcmVuYmVla0BsdW1jLm5sPC9BZGRyZXNzPjxXZWJf
VVJMPlBNOjIxNDE1MDUyPC9XZWJfVVJMPjxaWl9Kb3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0i
PkFubiBSaGV1bSBEaXM8L2Y+PC9aWl9Kb3VybmFsRnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9X
b3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkFsZXRhaGE8L0F1dGhvcj48WWVh
cj4yMDE1PC9ZZWFyPjxSZWNOdW0+MjkwMzwvUmVjTnVtPjxJRFRleHQ+T3B0aW1pc2F0aW9uIG9m
IGEgdHJlYXQtdG8tdGFyZ2V0IGFwcHJvYWNoIGluIHJoZXVtYXRvaWQgYXJ0aHJpdGlzOiBzdHJh
dGVnaWVzIGZvciB0aGUgMy1tb250aCB0aW1lIHBvaW50PC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0i
Sm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MjkwMzwvUmVmX0lE
PjxUaXRsZV9QcmltYXJ5Pk9wdGltaXNhdGlvbiBvZiBhIHRyZWF0LXRvLXRhcmdldCBhcHByb2Fj
aCBpbiByaGV1bWF0b2lkIGFydGhyaXRpczogc3RyYXRlZ2llcyBmb3IgdGhlIDMtbW9udGggdGlt
ZSBwb2ludDwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFsZXRhaGEsRC48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFsYXN0aSxGLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+U21vbGVuLEouUy48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5
PjIwMTUvOS8yOTwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5hbmFseXNpczwvS2V5d29yZHM+PEtl
eXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkF1c3RyaWE8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5EaXNlYXNlPC9LZXl3b3Jkcz48S2V5d29yZHM+bWV0aG9kczwvS2V5d29yZHM+PEtl
eXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jk
cz48S2V5d29yZHM+VGltZTwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+
PFBlcmlvZGljYWw+QW5uIFJoZXVtIERpczwvUGVyaW9kaWNhbD48TWlzY18zPmFubnJoZXVtZGlz
LTIwMTUtMjA4MzI0IFtwaWldOzEwLjExMzYvYW5ucmhldW1kaXMtMjAxNS0yMDgzMjQgW2RvaV08
L01pc2NfMz48QWRkcmVzcz5EaXZpc2lvbiBvZiBSaGV1bWF0b2xvZ3ksIE1lZGljYWwgVW5pdmVy
c2l0eSBWaWVubmEsIFZpZW5uYSwgQXVzdHJpYSYjeEE7RGl2aXNpb24gb2YgUmhldW1hdG9sb2d5
LCBNZWRpY2FsIFVuaXZlcnNpdHkgVmllbm5hLCBWaWVubmEsIEF1c3RyaWEmI3hBO0RpdmlzaW9u
IG9mIFJoZXVtYXRvbG9neSwgTWVkaWNhbCBVbml2ZXJzaXR5IFZpZW5uYSwgVmllbm5hLCBBdXN0
cmlhIFNlY29uZCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBIaWV0emluZyBIb3NwaXRhbCwgVmll
bm5hLCBBdXN0cmlhPC9BZGRyZXNzPjxXZWJfVVJMPlBNOjI2NDIwNTc3PC9XZWJfVVJMPjxaWl9K
b3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFubiBSaGV1bSBEaXM8L2Y+PC9aWl9Kb3VybmFs
RnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48
QXV0aG9yPkFsZXRhaGE8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxSZWNOdW0+MTE5NzwvUmVj
TnVtPjxJRFRleHQ+RGlzZWFzZSBhY3Rpdml0eSBlYXJseSBpbiB0aGUgY291cnNlIG9mIHRyZWF0
bWVudCBwcmVkaWN0cyByZXNwb25zZSB0byB0aGVyYXB5IGFmdGVyIG9uZSB5ZWFyIGluIHJoZXVt
YXRvaWQgYXJ0aHJpdGlzIHBhdGllbnRzPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+
PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MTE5NzwvUmVmX0lEPjxUaXRsZV9Q
cmltYXJ5PkRpc2Vhc2UgYWN0aXZpdHkgZWFybHkgaW4gdGhlIGNvdXJzZSBvZiB0cmVhdG1lbnQg
cHJlZGljdHMgcmVzcG9uc2UgdG8gdGhlcmFweSBhZnRlciBvbmUgeWVhciBpbiByaGV1bWF0b2lk
IGFydGhyaXRpcyBwYXRpZW50czwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFsZXRh
aGEsRC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZ1bm92aXRzLEouPC9BdXRo
b3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LZXlzdG9uZSxFLkMuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5TbW9sZW4sSi5TLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1By
aW1hcnk+MjAwNy85LzI4PC9EYXRlX1ByaW1hcnk+PEtleXdvcmRzPmFuYWx5c2lzPC9LZXl3b3Jk
cz48S2V5d29yZHM+QW5hbHlzaXMgb2YgVmFyaWFuY2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRo
cml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BdXN0cmlhPC9LZXl3b3Jkcz48S2V5d29yZHM+Q2xp
bmljYWwgVHJpYWxzPC9LZXl3b3Jkcz48S2V5d29yZHM+bWV0aG9kczwvS2V5d29yZHM+PEtleXdv
cmRzPk1ldGhvdHJleGF0ZTwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48
S2V5d29yZHM+Um9jIEN1cnZlPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFweTwvS2V5d29yZHM+
PEtleXdvcmRzPlRpbWU8L0tleXdvcmRzPjxLZXl3b3Jkcz5UdW1vciBOZWNyb3NpcyBGYWN0b3I8
L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjMyMjY8
L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjMyMzU8L0VuZF9QYWdlPjxQZXJpb2RpY2FsPkFydGhyaXRp
cyBSaGV1bTwvUGVyaW9kaWNhbD48Vm9sdW1lPjU2PC9Wb2x1bWU+PElzc3VlPjEwPC9Jc3N1ZT48
QWRkcmVzcz5NZWRpY2FsIFVuaXZlcnNpdHkgb2YgVmllbm5hLCBWaWVubmEsIEF1c3RyaWE8L0Fk
ZHJlc3M+PFdlYl9VUkw+UE06MTc5MDcxNjc8L1dlYl9VUkw+PFpaX0pvdXJuYWxGdWxsPjxmIG5h
bWU9IlN5c3RlbSI+QXJ0aHJpdGlzIFJoZXVtPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtm
b3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5TY2hpcHBl
cjwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJlY051bT4xNzM3PC9SZWNOdW0+PElEVGV4dD5U
aW1lIHRvIGFjaGlldmUgcmVtaXNzaW9uIGRldGVybWluZXMgdGltZSB0byBiZSBpbiByZW1pc3Np
b248L0lEVGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVm
X1R5cGU+PFJlZl9JRD4xNzM3PC9SZWZfSUQ+PFRpdGxlX1ByaW1hcnk+VGltZSB0byBhY2hpZXZl
IHJlbWlzc2lvbiBkZXRlcm1pbmVzIHRpbWUgdG8gYmUgaW4gcmVtaXNzaW9uPC9UaXRsZV9Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+U2NoaXBwZXIsTC5HLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+RnJhbnNlbixKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
ZGVuIEJyb2VkZXIsQS5BLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIFJp
ZWwsUC5MLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxMDwvRGF0ZV9QcmltYXJ5
PjxLZXl3b3Jkcz5BZHVsdDwvS2V5d29yZHM+PEtleXdvcmRzPkFnZWQ8L0tleXdvcmRzPjxLZXl3
b3Jkcz5BbnRpcmhldW1hdGljIEFnZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwv
S2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29y
ZHM+Q29ob3J0IFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5kaWFnbm9zaXM8L0tleXdvcmRz
PjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5GZW1hbGU8L0tleXdv
cmRzPjxLZXl3b3Jkcz5Gb2xsb3ctVXAgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPkh1bWFu
czwvS2V5d29yZHM+PEtleXdvcmRzPk1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+TWlkZGxlIEFnZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5OZXRoZXJs
YW5kczwvS2V5d29yZHM+PEtleXdvcmRzPk9kZHMgUmF0aW88L0tleXdvcmRzPjxLZXl3b3Jkcz5Q
YXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlByZWRpY3RpdmUgVmFsdWUgb2YgVGVzdHM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5Qcm9nbm9zaXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5SZWdyZXNzaW9u
IEFuYWx5c2lzPC9LZXl3b3Jkcz48S2V5d29yZHM+UmVtaXNzaW9uIEluZHVjdGlvbjwvS2V5d29y
ZHM+PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmV0cm9zcGVjdGl2ZSBT
dHVkaWVzPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jkcz48S2V5d29y
ZHM+U2V2ZXJpdHkgb2YgSWxsbmVzcyBJbmRleDwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcGV1
dGljIHVzZTwvS2V5d29yZHM+PEtleXdvcmRzPlRpbWU8L0tleXdvcmRzPjxLZXl3b3Jkcz5UaW1l
IEZhY3RvcnM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9Q
YWdlPlI5NzwvU3RhcnRfUGFnZT48UGVyaW9kaWNhbD5BcnRocml0aXMgUmVzIFRoZXIuPC9QZXJp
b2RpY2FsPjxWb2x1bWU+MTI8L1ZvbHVtZT48SXNzdWU+MzwvSXNzdWU+PEFkZHJlc3M+RGVwYXJ0
bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFJhZGJvdWQgVW5pdmVyc2l0eSBOaWptZWdlbiBNZWRpY2Fs
IENlbnRyZSwgR2VlcnQgR3Jvb3RlcGxlaW4gOCwgTmlqbWVnZW4sIDY1MDAgSEIsIFRoZSBOZXRo
ZXJsYW5kcy4gbHNjaGlwcGVyQHJldW1hLnVtY24ubmw8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjA0
ODc1MjA8L1dlYl9VUkw+PFpaX0pvdXJuYWxTdGRBYmJyZXY+PGYgbmFtZT0iU3lzdGVtIj5BcnRo
cml0aXMgUmVzIFRoZXIuPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48WlpfV29ya2Zvcm1JRD4x
PC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1hbj5=
ADDIN EN.CITE.DATA 31;87-89 exceptions pertain to those patients whose disease activity has been reduced to a level close to the treatment target. Regarding remission, EULAR and ACR have agreed on a Boolean and index-based definition.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA 22 Both correlate highly with the absence of subclinical synovitis by magnetic resonance imaging and sonographyPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbmdhbmF0aDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbmdhbmF0aDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+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ADDIN EN.CITE.DATA 90;91 and absence of progression of joint damage.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkthdmFuYXVnaDwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkthdmFuYXVnaDwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+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ADDIN EN.CITE.DATA 23 They can even be reliably used when drugs that interfere directly with the acute phase response are employed.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdlbm92ZXNlPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48
UmVjTnVtPjMwMzk8L1JlY051bT48SURUZXh0PkJhcmljaXRpbmliIGluIFBhdGllbnRzIHdpdGgg
UmVmcmFjdG9yeSBSaGV1bWF0b2lkIEFydGhyaXRpczwvSURUZXh0PjxNREwgUmVmX1R5cGU9Ikpv
dXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjMwMzk8L1JlZl9JRD48
VGl0bGVfUHJpbWFyeT5CYXJpY2l0aW5pYiBpbiBQYXRpZW50cyB3aXRoIFJlZnJhY3RvcnkgUmhl
dW1hdG9pZCBBcnRocml0aXM8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HZW5vdmVz
ZSxNLkMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LcmVtZXIsSi48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlphbWFuaSxPLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+THVkaXZpY28sQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5Pktyb2d1bGVjLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5YaWUsTC48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJlYXR0aWUsUy5ELjwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S29jaCxBLkUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5DYXJkaWxsbyxULkUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5Sb29uZXksVC5QLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TWFjaWFzLFcu
TC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlLEJvbm8gUy48L0F1dGhvcnNf
UHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNjaGxpY2h0aW5nLEQuRS48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlNtb2xlbixKLlMuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJp
bWFyeT4yMDE2LzMvMzE8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+YWR2ZXJzZSBlZmZlY3RzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+QWdlZDwvS2V5d29yZHM+PEtleXdvcmRzPmFudGFnb25pc3RzICZh
bXA7IGluaGliaXRvcnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BbnRpcmhldW1hdGljIEFnZW50czwv
S2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRp
cyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+QXpldGlkaW5lczwvS2V5d29yZHM+PEtl
eXdvcmRzPkMtUmVhY3RpdmUgUHJvdGVpbjwvS2V5d29yZHM+PEtleXdvcmRzPkNob2xlc3Rlcm9s
PC9LZXl3b3Jkcz48S2V5d29yZHM+Q3JlYXRpbmluZTwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vh
c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5G
ZW1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5IZWFsdGg8L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1h
bnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5JbmZlY3Rpb248L0tleXdvcmRzPjxLZXl3b3Jkcz5KYW51
cyBLaW5hc2UgMTwvS2V5d29yZHM+PEtleXdvcmRzPkphbnVzIEtpbmFzZSAyPC9LZXl3b3Jkcz48
S2V5d29yZHM+TG9naXN0aWMgTW9kZWxzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5d29y
ZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwvS2V5
d29yZHM+PEtleXdvcmRzPk11bHRpY2VudGVyIFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Q
YXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlByb3RlaW4gS2luYXNlIEluaGliaXRvcnM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9n
eTwvS2V5d29yZHM+PEtleXdvcmRzPlNldmVyaXR5IG9mIElsbG5lc3MgSW5kZXg8L0tleXdvcmRz
PjxLZXl3b3Jkcz5Ta2luPC9LZXl3b3Jkcz48S2V5d29yZHM+U3Ryb2tlPC9LZXl3b3Jkcz48S2V5
d29yZHM+U3VsZm9uYW1pZGVzPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFwZXV0aWMgdXNlPC9L
ZXl3b3Jkcz48S2V5d29yZHM+VHVtb3IgTmVjcm9zaXMgRmFjdG9yPC9LZXl3b3Jkcz48UmVwcmlu
dD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4xMjQzPC9TdGFydF9QYWdlPjxFbmRf
UGFnZT4xMjUyPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5OLkVuZ2wuSi5NZWQuPC9QZXJpb2RpY2Fs
PjxWb2x1bWU+Mzc0PC9Wb2x1bWU+PElzc3VlPjEzPC9Jc3N1ZT48TWlzY18zPjEwLjEwNTYvTkVK
TW9hMTUwNzI0NyBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPkZyb20gdGhlIFN0YW5mb3JkIFVuaXZl
cnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7IEFsYmFueSBNZWRp
Y2FsIENvbGxlZ2UsIEFsYmFueSwgTlkgKCBKLksuKTsgUmhldW1hemVudHJ1bSBGYXZvcml0ZW4g
KE8uWi4pIGFuZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAoIEouUy5TLikgLSBi
b3RoIGluIFZpZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxlaGVtLCBQQSAoQy5M
Lik7IFJoZXVtYXRvbG9neSBDbGluaWMsIE1BSy1NRUQsIE5hZGFyenluLCBQb2xhbmQgKE0uSy4p
OyBhbmQgRWxpIExpbGx5LCBJbmRpYW5hcG9saXMgKEwuWC4sIFMuRC5CLiwgQS5FLksuLCBULkUu
Qy4sIFQuUC5SLiwgVy5MLk0uLCBTLkIuLCBELkUuUy4pJiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBV
bml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFsdG8sIENBIChNLkMuRy4pOyBBbGJhbnkg
TWVkaWNhbCBDb2xsZWdlLCBBbGJhbnksIE5ZICggSi5LLik7IFJoZXVtYXplbnRydW0gRmF2b3Jp
dGVuIChPLlouKSBhbmQgdGhlIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEgKCBKLlMuUy4p
IC0gYm90aCBpbiBWaWVubmE7IEVhc3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEg
KEMuTC4pOyBSaGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUstTUVELCBOYWRhcnp5biwgUG9sYW5kIChN
LksuKTsgYW5kIEVsaSBMaWxseSwgSW5kaWFuYXBvbGlzIChMLlguLCBTLkQuQi4sIEEuRS5LLiwg
VC5FLkMuLCBULlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5FLlMuKSYjeEE7RnJvbSB0aGUgU3RhbmZv
cmQgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgUGFsbyBBbHRvLCBDQSAoTS5DLkcuKTsgQWxi
YW55IE1lZGljYWwgQ29sbGVnZSwgQWxiYW55LCBOWSAoIEouSy4pOyBSaGV1bWF6ZW50cnVtIEZh
dm9yaXRlbiAoTy5aLikgYW5kIHRoZSBNZWRpY2FsIFVuaXZlcnNpdHkgb2YgVmllbm5hICggSi5T
LlMuKSAtIGJvdGggaW4gVmllbm5hOyBFYXN0IFBlbm4gUmhldW1hdG9sb2d5LCBCZXRobGVoZW0s
IFBBIChDLkwuKTsgUmhldW1hdG9sb2d5IENsaW5pYywgTUFLLU1FRCwgTmFkYXJ6eW4sIFBvbGFu
ZCAoTS5LLik7IGFuZCBFbGkgTGlsbHksIEluZGlhbmFwb2xpcyAoTC5YLiwgUy5ELkIuLCBBLkUu
Sy4sIFQuRS5DLiwgVC5QLlIuLCBXLkwuTS4sIFMuQi4sIEQuRS5TLikmI3hBO0Zyb20gdGhlIFN0
YW5mb3JkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7
IEFsYmFueSBNZWRpY2FsIENvbGxlZ2UsIEFsYmFueSwgTlkgKCBKLksuKTsgUmhldW1hemVudHJ1
bSBGYXZvcml0ZW4gKE8uWi4pIGFuZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAo
IEouUy5TLikgLSBib3RoIGluIFZpZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxl
aGVtLCBQQSAoQy5MLik7IFJoZXVtYXRvbG9neSBDbGluaWMsIE1BSy1NRUQsIE5hZGFyenluLCBQ
b2xhbmQgKE0uSy4pOyBhbmQgRWxpIExpbGx5LCBJbmRpYW5hcG9saXMgKEwuWC4sIFMuRC5CLiwg
QS5FLksuLCBULkUuQy4sIFQuUC5SLiwgVy5MLk0uLCBTLkIuLCBELkUuUy4pJiN4QTtGcm9tIHRo
ZSBTdGFuZm9yZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFsdG8sIENBIChNLkMu
Ry4pOyBBbGJhbnkgTWVkaWNhbCBDb2xsZWdlLCBBbGJhbnksIE5ZICggSi5LLik7IFJoZXVtYXpl
bnRydW0gRmF2b3JpdGVuIChPLlouKSBhbmQgdGhlIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVu
bmEgKCBKLlMuUy4pIC0gYm90aCBpbiBWaWVubmE7IEVhc3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJl
dGhsZWhlbSwgUEEgKEMuTC4pOyBSaGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUstTUVELCBOYWRhcnp5
biwgUG9sYW5kIChNLksuKTsgYW5kIEVsaSBMaWxseSwgSW5kaWFuYXBvbGlzIChMLlguLCBTLkQu
Qi4sIEEuRS5LLiwgVC5FLkMuLCBULlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5FLlMuKSYjeEE7RnJv
bSB0aGUgU3RhbmZvcmQgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgUGFsbyBBbHRvLCBDQSAo
TS5DLkcuKTsgQWxiYW55IE1lZGljYWwgQ29sbGVnZSwgQWxiYW55LCBOWSAoIEouSy4pOyBSaGV1
bWF6ZW50cnVtIEZhdm9yaXRlbiAoTy5aLikgYW5kIHRoZSBNZWRpY2FsIFVuaXZlcnNpdHkgb2Yg
Vmllbm5hICggSi5TLlMuKSAtIGJvdGggaW4gVmllbm5hOyBFYXN0IFBlbm4gUmhldW1hdG9sb2d5
LCBCZXRobGVoZW0sIFBBIChDLkwuKTsgUmhldW1hdG9sb2d5IENsaW5pYywgTUFLLU1FRCwgTmFk
YXJ6eW4sIFBvbGFuZCAoTS5LLik7IGFuZCBFbGkgTGlsbHksIEluZGlhbmFwb2xpcyAoTC5YLiwg
Uy5ELkIuLCBBLkUuSy4sIFQuRS5DLiwgVC5QLlIuLCBXLkwuTS4sIFMuQi4sIEQuRS5TLikmI3hB
O0Zyb20gdGhlIFN0YW5mb3JkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBhbG8gQWx0bywg
Q0EgKE0uQy5HLik7IEFsYmFueSBNZWRpY2FsIENvbGxlZ2UsIEFsYmFueSwgTlkgKCBKLksuKTsg
UmhldW1hemVudHJ1bSBGYXZvcml0ZW4gKE8uWi4pIGFuZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5
IG9mIFZpZW5uYSAoIEouUy5TLikgLSBib3RoIGluIFZpZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRv
bG9neSwgQmV0aGxlaGVtLCBQQSAoQy5MLik7IFJoZXVtYXRvbG9neSBDbGluaWMsIE1BSy1NRUQs
IE5hZGFyenluLCBQb2xhbmQgKE0uSy4pOyBhbmQgRWxpIExpbGx5LCBJbmRpYW5hcG9saXMgKEwu
WC4sIFMuRC5CLiwgQS5FLksuLCBULkUuQy4sIFQuUC5SLiwgVy5MLk0uLCBTLkIuLCBELkUuUy4p
JiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFs
dG8sIENBIChNLkMuRy4pOyBBbGJhbnkgTWVkaWNhbCBDb2xsZWdlLCBBbGJhbnksIE5ZICggSi5L
Lik7IFJoZXVtYXplbnRydW0gRmF2b3JpdGVuIChPLlouKSBhbmQgdGhlIE1lZGljYWwgVW5pdmVy
c2l0eSBvZiBWaWVubmEgKCBKLlMuUy4pIC0gYm90aCBpbiBWaWVubmE7IEVhc3QgUGVubiBSaGV1
bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEgKEMuTC4pOyBSaGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUst
TUVELCBOYWRhcnp5biwgUG9sYW5kIChNLksuKTsgYW5kIEVsaSBMaWxseSwgSW5kaWFuYXBvbGlz
IChMLlguLCBTLkQuQi4sIEEuRS5LLiwgVC5FLkMuLCBULlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5F
LlMuKSYjeEE7RnJvbSB0aGUgU3RhbmZvcmQgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgUGFs
byBBbHRvLCBDQSAoTS5DLkcuKTsgQWxiYW55IE1lZGljYWwgQ29sbGVnZSwgQWxiYW55LCBOWSAo
IEouSy4pOyBSaGV1bWF6ZW50cnVtIEZhdm9yaXRlbiAoTy5aLikgYW5kIHRoZSBNZWRpY2FsIFVu
aXZlcnNpdHkgb2YgVmllbm5hICggSi5TLlMuKSAtIGJvdGggaW4gVmllbm5hOyBFYXN0IFBlbm4g
UmhldW1hdG9sb2d5LCBCZXRobGVoZW0sIFBBIChDLkwuKTsgUmhldW1hdG9sb2d5IENsaW5pYywg
TUFLLU1FRCwgTmFkYXJ6eW4sIFBvbGFuZCAoTS5LLik7IGFuZCBFbGkgTGlsbHksIEluZGlhbmFw
b2xpcyAoTC5YLiwgUy5ELkIuLCBBLkUuSy4sIFQuRS5DLiwgVC5QLlIuLCBXLkwuTS4sIFMuQi4s
IEQuRS5TLikmI3hBO0Zyb20gdGhlIFN0YW5mb3JkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIs
IFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7IEFsYmFueSBNZWRpY2FsIENvbGxlZ2UsIEFsYmFueSwg
TlkgKCBKLksuKTsgUmhldW1hemVudHJ1bSBGYXZvcml0ZW4gKE8uWi4pIGFuZCB0aGUgTWVkaWNh
bCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAoIEouUy5TLikgLSBib3RoIGluIFZpZW5uYTsgRWFzdCBQ
ZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxlaGVtLCBQQSAoQy5MLik7IFJoZXVtYXRvbG9neSBDbGlu
aWMsIE1BSy1NRUQsIE5hZGFyenluLCBQb2xhbmQgKE0uSy4pOyBhbmQgRWxpIExpbGx5LCBJbmRp
YW5hcG9saXMgKEwuWC4sIFMuRC5CLiwgQS5FLksuLCBULkUuQy4sIFQuUC5SLiwgVy5MLk0uLCBT
LkIuLCBELkUuUy4pJiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2Vu
dGVyLCBQYWxvIEFsdG8sIENBIChNLkMuRy4pOyBBbGJhbnkgTWVkaWNhbCBDb2xsZWdlLCBBbGJh
bnksIE5ZICggSi5LLik7IFJoZXVtYXplbnRydW0gRmF2b3JpdGVuIChPLlouKSBhbmQgdGhlIE1l
ZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEgKCBKLlMuUy4pIC0gYm90aCBpbiBWaWVubmE7IEVh
c3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEgKEMuTC4pOyBSaGV1bWF0b2xvZ3kg
Q2xpbmljLCBNQUstTUVELCBOYWRhcnp5biwgUG9sYW5kIChNLksuKTsgYW5kIEVsaSBMaWxseSwg
SW5kaWFuYXBvbGlzIChMLlguLCBTLkQuQi4sIEEuRS5LLiwgVC5FLkMuLCBULlAuUi4sIFcuTC5N
LiwgUy5CLiwgRC5FLlMuKSYjeEE7RnJvbSB0aGUgU3RhbmZvcmQgVW5pdmVyc2l0eSBNZWRpY2Fs
IENlbnRlciwgUGFsbyBBbHRvLCBDQSAoTS5DLkcuKTsgQWxiYW55IE1lZGljYWwgQ29sbGVnZSwg
QWxiYW55LCBOWSAoIEouSy4pOyBSaGV1bWF6ZW50cnVtIEZhdm9yaXRlbiAoTy5aLikgYW5kIHRo
ZSBNZWRpY2FsIFVuaXZlcnNpdHkgb2YgVmllbm5hICggSi5TLlMuKSAtIGJvdGggaW4gVmllbm5h
OyBFYXN0IFBlbm4gUmhldW1hdG9sb2d5LCBCZXRobGVoZW0sIFBBIChDLkwuKTsgUmhldW1hdG9s
b2d5IENsaW5pYywgTUFLLU1FRCwgTmFkYXJ6eW4sIFBvbGFuZCAoTS5LLik7IGFuZCBFbGkgTGls
bHksIEluZGlhbmFwb2xpcyAoTC5YLiwgUy5ELkIuLCBBLkUuSy4sIFQuRS5DLiwgVC5QLlIuLCBX
LkwuTS4sIFMuQi4sIEQuRS5TLikmI3hBO0Zyb20gdGhlIFN0YW5mb3JkIFVuaXZlcnNpdHkgTWVk
aWNhbCBDZW50ZXIsIFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7IEFsYmFueSBNZWRpY2FsIENvbGxl
Z2UsIEFsYmFueSwgTlkgKCBKLksuKTsgUmhldW1hemVudHJ1bSBGYXZvcml0ZW4gKE8uWi4pIGFu
ZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAoIEouUy5TLikgLSBib3RoIGluIFZp
ZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxlaGVtLCBQQSAoQy5MLik7IFJoZXVt
YXRvbG9neSBDbGluaWMsIE1BSy1NRUQsIE5hZGFyenluLCBQb2xhbmQgKE0uSy4pOyBhbmQgRWxp
IExpbGx5LCBJbmRpYW5hcG9saXMgKEwuWC4sIFMuRC5CLiwgQS5FLksuLCBULkUuQy4sIFQuUC5S
LiwgVy5MLk0uLCBTLkIuLCBELkUuUy4pJiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBVbml2ZXJzaXR5
IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFsdG8sIENBIChNLkMuRy4pOyBBbGJhbnkgTWVkaWNhbCBD
b2xsZWdlLCBBbGJhbnksIE5ZICggSi5LLik7IFJoZXVtYXplbnRydW0gRmF2b3JpdGVuIChPLlou
KSBhbmQgdGhlIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEgKCBKLlMuUy4pIC0gYm90aCBp
biBWaWVubmE7IEVhc3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEgKEMuTC4pOyBS
aGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUstTUVELCBOYWRhcnp5biwgUG9sYW5kIChNLksuKTsgYW5k
IEVsaSBMaWxseSwgSW5kaWFuYXBvbGlzIChMLlguLCBTLkQuQi4sIEEuRS5LLiwgVC5FLkMuLCBU
LlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5FLlMuKTwvQWRkcmVzcz48V2ViX1VSTD5QTToyNzAyODkx
NDwvV2ViX1VSTD48WlpfSm91cm5hbFN0ZEFiYnJldj48ZiBuYW1lPSJTeXN0ZW0iPk4uRW5nbC5K
Lk1lZC48L2Y+PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtm
b3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRob3I+R2FiYXk8L0F1dGhvcj48WWVhcj4yMDEz
PC9ZZWFyPjxSZWNOdW0+MjYyNTwvUmVjTnVtPjxJRFRleHQ+VG9jaWxpenVtYWIgbW9ub3RoZXJh
cHkgdmVyc3VzIGFkYWxpbXVtYWIgbW9ub3RoZXJhcHkgZm9yIHRyZWF0bWVudCBvZiByaGV1bWF0
b2lkIGFydGhyaXRpcyAoQURBQ1RBKTogYSByYW5kb21pc2VkLCBkb3VibGUtYmxpbmQsIGNvbnRy
b2xsZWQgcGhhc2UgNCB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZf
VHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjI2MjU8L1JlZl9JRD48VGl0bGVfUHJpbWFy
eT5Ub2NpbGl6dW1hYiBtb25vdGhlcmFweSB2ZXJzdXMgYWRhbGltdW1hYiBtb25vdGhlcmFweSBm
b3IgdHJlYXRtZW50IG9mIHJoZXVtYXRvaWQgYXJ0aHJpdGlzIChBREFDVEEpOiBhIHJhbmRvbWlz
ZWQsIGRvdWJsZS1ibGluZCwgY29udHJvbGxlZCBwaGFzZSA0IHRyaWFsPC9UaXRsZV9QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+R2FiYXksQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkVtZXJ5LFAuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52YW4sVm9sbGVu
aG92ZW4gUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkRpa3JhbmlhbixBLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QWx0ZW4sUi48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlBhdmVsa2EsSy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PktsZWFybWFuLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NdXNz
ZWxtYW4sRC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFnYXJ3YWwsUy48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkdyZWVuLEouPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5LYXZhbmF1Z2gsQS48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9Qcmlt
YXJ5PjIwMTMvNS80PC9EYXRlX1ByaW1hcnk+PEtleXdvcmRzPkFkdWx0PC9LZXl3b3Jkcz48S2V5
d29yZHM+QWdlZDwvS2V5d29yZHM+PEtleXdvcmRzPkFudGlib2RpZXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5BbnRpYm9kaWVzLE1vbm9jbG9uYWwsSHVtYW5pemVkPC9LZXl3b3Jkcz48S2V5d29yZHM+
QW50aXJoZXVtYXRpYyBBZ2VudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdv
cmRzPjxLZXl3b3Jkcz5BcnRocml0aXMsUmhldW1hdG9pZDwvS2V5d29yZHM+PEtleXdvcmRzPkNs
aW5pY2FsIFRyaWFsczwvS2V5d29yZHM+PEtleXdvcmRzPkNvbXBhcmF0aXZlIFN0dWR5PC9LZXl3
b3Jkcz48S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRzPkRvdWJsZS1CbGluZCBN
ZXRob2Q8L0tleXdvcmRzPjxLZXl3b3Jkcz5FdXJvcGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5GZW1h
bGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5Ib3NwaXRhbHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1h
bnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5JbnRlcmxldWtpbi02PC9LZXl3b3Jkcz48S2V5d29yZHM+
Sm9pbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5d29yZHM+PEtleXdvcmRzPm1ldGhv
ZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5N
aWRkbGUgQWdlZDwvS2V5d29yZHM+PEtleXdvcmRzPk11bHRpY2VudGVyIFN0dWRpZXM8L0tleXdv
cmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3
b3Jkcz48S2V5d29yZHM+U2FmZXR5PC9LZXl3b3Jkcz48S2V5d29yZHM+U3dpdHplcmxhbmQ8L0tl
eXdvcmRzPjxLZXl3b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVy
YXB5PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4x
NTQxPC9TdGFydF9QYWdlPjxFbmRfUGFnZT4xNTUwPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5MYW5j
ZXQ8L1BlcmlvZGljYWw+PFZvbHVtZT4zODE8L1ZvbHVtZT48SXNzdWU+OTg3NzwvSXNzdWU+PE1p
c2NfMz5TMDE0MC02NzM2KDEzKTYwMjUwLTAgW3BpaV07MTAuMTAxNi9TMDE0MC02NzM2KDEzKTYw
MjUwLTAgW2RvaV08L01pc2NfMz48QWRkcmVzcz5Vbml2ZXJzaXR5IEhvc3BpdGFscyBvZiBHZW5l
dmEsIEdlbmV2YSwgU3dpdHplcmxhbmQ8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjM1MTUxNDI8L1dl
Yl9VUkw+PFpaX0pvdXJuYWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+TGFuY2V0PC9mPjwvWlpfSm91
cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENp
dGU+PEF1dGhvcj5TbW9sZW48L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNOdW0+MTc0Mjwv
UmVjTnVtPjxJRFRleHQ+SW50ZXJsZXVraW4tNiByZWNlcHRvciBpbmhpYml0aW9uIHdpdGggdG9j
aWxpenVtYWIgYW5kIGF0dGFpbm1lbnQgb2YgZGlzZWFzZSByZW1pc3Npb24gaW4gcmhldW1hdG9p
ZCBhcnRocml0aXM6IFRoZSByb2xlIG9mIGFjdXRlLXBoYXNlIHJlYWN0YW50czwvSURUZXh0PjxN
REwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lE
PjE3NDI8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5JbnRlcmxldWtpbi02IHJlY2VwdG9yIGluaGli
aXRpb24gd2l0aCB0b2NpbGl6dW1hYiBhbmQgYXR0YWlubWVudCBvZiBkaXNlYXNlIHJlbWlzc2lv
biBpbiByaGV1bWF0b2lkIGFydGhyaXRpczogVGhlIHJvbGUgb2YgYWN1dGUtcGhhc2UgcmVhY3Rh
bnRzPC9UaXRsZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U21vbGVuLEouUy48L0F1dGhvcnNf
UHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFsZXRhaGEsRC48L0F1dGhvcnNfUHJpbWFyeT48RGF0
ZV9QcmltYXJ5PjIwMTEvMTwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdv
cmRzPjxLZXl3b3Jkcz5BdXN0cmlhPC9LZXl3b3Jkcz48S2V5d29yZHM+SW50ZXJsZXVraW4tNjwv
S2V5d29yZHM+PEtleXdvcmRzPkpvaW50czwvS2V5d29yZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9n
eTwvS2V5d29yZHM+PEtleXdvcmRzPlR1bW9yIE5lY3Jvc2lzIEZhY3RvcjwvS2V5d29yZHM+PFJl
cHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+NDM8L1N0YXJ0X1BhZ2U+PEVu
ZF9QYWdlPjUyPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5BcnRocml0aXMgUmhldW08L1BlcmlvZGlj
YWw+PFZvbHVtZT42MzwvVm9sdW1lPjxJc3N1ZT4xPC9Jc3N1ZT48QWRkcmVzcz5NZWRpY2FsIFVu
aXZlcnNpdHkgb2YgVmllbm5hIGFuZCBIaWV0emluZyBIb3NwaXRhbCwgVmllbm5hLCBBdXN0cmlh
LiBqb3NlZi5zbW9sZW5Ad2llbmthdi5hdCwgSm9zZWYuc21vbGVuQG1lZHVuaXdpZW4uYWMuYXQ8
L0FkZHJlc3M+PFdlYl9VUkw+UE06MjEyMDQxMDM8L1dlYl9VUkw+PFpaX0pvdXJuYWxGdWxsPjxm
IG5hbWU9IlN5c3RlbSI+QXJ0aHJpdGlzIFJoZXVtPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dv
cmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5GbGVp
c2NobWFubjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051bT4yODM5PC9SZWNOdW0+PElE
VGV4dD5Ib3cgbXVjaCBkb2VzIERpc2Vhc2UgQWN0aXZpdHkgU2NvcmUgaW4gMjggam9pbnRzIEVT
UiBhbmQgQ1JQIGNhbGN1bGF0aW9ucyB1bmRlcmVzdGltYXRlIGRpc2Vhc2UgYWN0aXZpdHkgY29t
cGFyZWQgd2l0aCB0aGUgU2ltcGxpZmllZCBEaXNlYXNlIEFjdGl2aXR5IEluZGV4PzwvSURUZXh0
PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVm
X0lEPjI4Mzk8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5Ib3cgbXVjaCBkb2VzIERpc2Vhc2UgQWN0
aXZpdHkgU2NvcmUgaW4gMjggam9pbnRzIEVTUiBhbmQgQ1JQIGNhbGN1bGF0aW9ucyB1bmRlcmVz
dGltYXRlIGRpc2Vhc2UgYWN0aXZpdHkgY29tcGFyZWQgd2l0aCB0aGUgU2ltcGxpZmllZCBEaXNl
YXNlIEFjdGl2aXR5IEluZGV4PzwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZsZWlz
Y2htYW5uLFIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52YW4gZGVyIEhlaWpk
ZSxELjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S29lbmlnLEEuUy48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlBlZGVyc2VuLFIuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5TenVtc2tpLEEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5NYXJzaGFsbCxMLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QmFuYW5p
cyxFLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxNC84LzIwPC9EYXRlX1ByaW1h
cnk+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVhY3RpdmUgUHJv
dGVpbjwvS2V5d29yZHM+PEtleXdvcmRzPkNsaW5pY2FsIFRyaWFsczwvS2V5d29yZHM+PEtleXdv
cmRzPkRpc2Vhc2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5Kb2ludHM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+TmV0aGVybGFuZHM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlBlbm5zeWx2YW5pYTwvS2V5d29yZHM+
PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3
b3Jkcz48S2V5d29yZHM+VGV4YXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXBy
aW50PjxQZXJpb2RpY2FsPkFubiBSaGV1bSBEaXM8L1BlcmlvZGljYWw+PE1pc2NfMz5hbm5yaGV1
bWRpcy0yMDEzLTIwNDkyMCBbcGlpXTsxMC4xMTM2L2FubnJoZXVtZGlzLTIwMTMtMjA0OTIwIFtk
b2ldPC9NaXNjXzM+PEFkZHJlc3M+TWV0cm9wbGV4IENsaW5pY2FsIFJlc2VhcmNoIENlbnRlciwg
VW5pdmVyc2l0eSBvZiBUZXhhcyBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywg
VGV4YXMsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIExlaWRlbiBVbml2ZXJz
aXR5IE1lZGljYWwgQ2VudGVyLCBMZWlkZW4sIFRoZSBOZXRoZXJsYW5kcyYjeEE7RGVwYXJ0bWVu
dCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIEluYywgQ29sbGVnZXZpbGxlLCBQZW5uc3lsdmFu
aWEsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIEluYywgQ29s
bGVnZXZpbGxlLCBQZW5uc3lsdmFuaWEsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBTcGVjaWFsdHkg
Q2FyZSwgUGZpemVyIEluYywgQ29sbGVnZXZpbGxlLCBQZW5uc3lsdmFuaWEsIFVTQSYjeEE7RGVw
YXJ0bWVudCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIEluYywgQ29sbGVnZXZpbGxlLCBQZW5u
c3lsdmFuaWEsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIElu
YywgQ29sbGVnZXZpbGxlLCBQZW5uc3lsdmFuaWEsIFVTQTwvQWRkcmVzcz48V2ViX1VSTD5QTToy
NTE0MzUyMjwvV2ViX1VSTD48WlpfSm91cm5hbEZ1bGw+PGYgbmFtZT0iU3lzdGVtIj5Bbm4gUmhl
dW0gRGlzPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1J
RD48L01ETD48L0NpdGU+PC9SZWZtYW4+
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdlbm92ZXNlPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN EN.CITE.DATA 92-95 Low disease activity also needs to be properly defined and measured: measures that highly weigh CRP or ESR (e.g. the DAS28) may not convey sufficiently reliable results when used with agents that interfere with the acute phase response, such as anti-cytokine agents (especially IL-6 inhibitors) or Jak inhibitors.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdlbm92ZXNlPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdlbm92ZXNlPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48
UmVjTnVtPjMwMzk8L1JlY051bT48SURUZXh0PkJhcmljaXRpbmliIGluIFBhdGllbnRzIHdpdGgg
UmVmcmFjdG9yeSBSaGV1bWF0b2lkIEFydGhyaXRpczwvSURUZXh0PjxNREwgUmVmX1R5cGU9Ikpv
dXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjMwMzk8L1JlZl9JRD48
VGl0bGVfUHJpbWFyeT5CYXJpY2l0aW5pYiBpbiBQYXRpZW50cyB3aXRoIFJlZnJhY3RvcnkgUmhl
dW1hdG9pZCBBcnRocml0aXM8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HZW5vdmVz
ZSxNLkMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LcmVtZXIsSi48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlphbWFuaSxPLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+THVkaXZpY28sQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5Pktyb2d1bGVjLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5YaWUsTC48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJlYXR0aWUsUy5ELjwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S29jaCxBLkUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5DYXJkaWxsbyxULkUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5Sb29uZXksVC5QLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TWFjaWFzLFcu
TC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlLEJvbm8gUy48L0F1dGhvcnNf
UHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNjaGxpY2h0aW5nLEQuRS48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PlNtb2xlbixKLlMuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJp
bWFyeT4yMDE2LzMvMzE8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+YWR2ZXJzZSBlZmZlY3RzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+QWdlZDwvS2V5d29yZHM+PEtleXdvcmRzPmFudGFnb25pc3RzICZh
bXA7IGluaGliaXRvcnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BbnRpcmhldW1hdGljIEFnZW50czwv
S2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRp
cyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+QXpldGlkaW5lczwvS2V5d29yZHM+PEtl
eXdvcmRzPkMtUmVhY3RpdmUgUHJvdGVpbjwvS2V5d29yZHM+PEtleXdvcmRzPkNob2xlc3Rlcm9s
PC9LZXl3b3Jkcz48S2V5d29yZHM+Q3JlYXRpbmluZTwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vh
c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5G
ZW1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5IZWFsdGg8L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1h
bnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5JbmZlY3Rpb248L0tleXdvcmRzPjxLZXl3b3Jkcz5KYW51
cyBLaW5hc2UgMTwvS2V5d29yZHM+PEtleXdvcmRzPkphbnVzIEtpbmFzZSAyPC9LZXl3b3Jkcz48
S2V5d29yZHM+TG9naXN0aWMgTW9kZWxzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5d29y
ZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwvS2V5
d29yZHM+PEtleXdvcmRzPk11bHRpY2VudGVyIFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Q
YXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlByb3RlaW4gS2luYXNlIEluaGliaXRvcnM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9n
eTwvS2V5d29yZHM+PEtleXdvcmRzPlNldmVyaXR5IG9mIElsbG5lc3MgSW5kZXg8L0tleXdvcmRz
PjxLZXl3b3Jkcz5Ta2luPC9LZXl3b3Jkcz48S2V5d29yZHM+U3Ryb2tlPC9LZXl3b3Jkcz48S2V5
d29yZHM+U3VsZm9uYW1pZGVzPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFwZXV0aWMgdXNlPC9L
ZXl3b3Jkcz48S2V5d29yZHM+VHVtb3IgTmVjcm9zaXMgRmFjdG9yPC9LZXl3b3Jkcz48UmVwcmlu
dD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4xMjQzPC9TdGFydF9QYWdlPjxFbmRf
UGFnZT4xMjUyPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5OLkVuZ2wuSi5NZWQuPC9QZXJpb2RpY2Fs
PjxWb2x1bWU+Mzc0PC9Wb2x1bWU+PElzc3VlPjEzPC9Jc3N1ZT48TWlzY18zPjEwLjEwNTYvTkVK
TW9hMTUwNzI0NyBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPkZyb20gdGhlIFN0YW5mb3JkIFVuaXZl
cnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7IEFsYmFueSBNZWRp
Y2FsIENvbGxlZ2UsIEFsYmFueSwgTlkgKCBKLksuKTsgUmhldW1hemVudHJ1bSBGYXZvcml0ZW4g
KE8uWi4pIGFuZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAoIEouUy5TLikgLSBi
b3RoIGluIFZpZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxlaGVtLCBQQSAoQy5M
Lik7IFJoZXVtYXRvbG9neSBDbGluaWMsIE1BSy1NRUQsIE5hZGFyenluLCBQb2xhbmQgKE0uSy4p
OyBhbmQgRWxpIExpbGx5LCBJbmRpYW5hcG9saXMgKEwuWC4sIFMuRC5CLiwgQS5FLksuLCBULkUu
Qy4sIFQuUC5SLiwgVy5MLk0uLCBTLkIuLCBELkUuUy4pJiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBV
bml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFsdG8sIENBIChNLkMuRy4pOyBBbGJhbnkg
TWVkaWNhbCBDb2xsZWdlLCBBbGJhbnksIE5ZICggSi5LLik7IFJoZXVtYXplbnRydW0gRmF2b3Jp
dGVuIChPLlouKSBhbmQgdGhlIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEgKCBKLlMuUy4p
IC0gYm90aCBpbiBWaWVubmE7IEVhc3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEg
KEMuTC4pOyBSaGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUstTUVELCBOYWRhcnp5biwgUG9sYW5kIChN
LksuKTsgYW5kIEVsaSBMaWxseSwgSW5kaWFuYXBvbGlzIChMLlguLCBTLkQuQi4sIEEuRS5LLiwg
VC5FLkMuLCBULlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5FLlMuKSYjeEE7RnJvbSB0aGUgU3RhbmZv
cmQgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgUGFsbyBBbHRvLCBDQSAoTS5DLkcuKTsgQWxi
YW55IE1lZGljYWwgQ29sbGVnZSwgQWxiYW55LCBOWSAoIEouSy4pOyBSaGV1bWF6ZW50cnVtIEZh
dm9yaXRlbiAoTy5aLikgYW5kIHRoZSBNZWRpY2FsIFVuaXZlcnNpdHkgb2YgVmllbm5hICggSi5T
LlMuKSAtIGJvdGggaW4gVmllbm5hOyBFYXN0IFBlbm4gUmhldW1hdG9sb2d5LCBCZXRobGVoZW0s
IFBBIChDLkwuKTsgUmhldW1hdG9sb2d5IENsaW5pYywgTUFLLU1FRCwgTmFkYXJ6eW4sIFBvbGFu
ZCAoTS5LLik7IGFuZCBFbGkgTGlsbHksIEluZGlhbmFwb2xpcyAoTC5YLiwgUy5ELkIuLCBBLkUu
Sy4sIFQuRS5DLiwgVC5QLlIuLCBXLkwuTS4sIFMuQi4sIEQuRS5TLikmI3hBO0Zyb20gdGhlIFN0
YW5mb3JkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7
IEFsYmFueSBNZWRpY2FsIENvbGxlZ2UsIEFsYmFueSwgTlkgKCBKLksuKTsgUmhldW1hemVudHJ1
bSBGYXZvcml0ZW4gKE8uWi4pIGFuZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAo
IEouUy5TLikgLSBib3RoIGluIFZpZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxl
aGVtLCBQQSAoQy5MLik7IFJoZXVtYXRvbG9neSBDbGluaWMsIE1BSy1NRUQsIE5hZGFyenluLCBQ
b2xhbmQgKE0uSy4pOyBhbmQgRWxpIExpbGx5LCBJbmRpYW5hcG9saXMgKEwuWC4sIFMuRC5CLiwg
QS5FLksuLCBULkUuQy4sIFQuUC5SLiwgVy5MLk0uLCBTLkIuLCBELkUuUy4pJiN4QTtGcm9tIHRo
ZSBTdGFuZm9yZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFsdG8sIENBIChNLkMu
Ry4pOyBBbGJhbnkgTWVkaWNhbCBDb2xsZWdlLCBBbGJhbnksIE5ZICggSi5LLik7IFJoZXVtYXpl
bnRydW0gRmF2b3JpdGVuIChPLlouKSBhbmQgdGhlIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVu
bmEgKCBKLlMuUy4pIC0gYm90aCBpbiBWaWVubmE7IEVhc3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJl
dGhsZWhlbSwgUEEgKEMuTC4pOyBSaGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUstTUVELCBOYWRhcnp5
biwgUG9sYW5kIChNLksuKTsgYW5kIEVsaSBMaWxseSwgSW5kaWFuYXBvbGlzIChMLlguLCBTLkQu
Qi4sIEEuRS5LLiwgVC5FLkMuLCBULlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5FLlMuKSYjeEE7RnJv
bSB0aGUgU3RhbmZvcmQgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgUGFsbyBBbHRvLCBDQSAo
TS5DLkcuKTsgQWxiYW55IE1lZGljYWwgQ29sbGVnZSwgQWxiYW55LCBOWSAoIEouSy4pOyBSaGV1
bWF6ZW50cnVtIEZhdm9yaXRlbiAoTy5aLikgYW5kIHRoZSBNZWRpY2FsIFVuaXZlcnNpdHkgb2Yg
Vmllbm5hICggSi5TLlMuKSAtIGJvdGggaW4gVmllbm5hOyBFYXN0IFBlbm4gUmhldW1hdG9sb2d5
LCBCZXRobGVoZW0sIFBBIChDLkwuKTsgUmhldW1hdG9sb2d5IENsaW5pYywgTUFLLU1FRCwgTmFk
YXJ6eW4sIFBvbGFuZCAoTS5LLik7IGFuZCBFbGkgTGlsbHksIEluZGlhbmFwb2xpcyAoTC5YLiwg
Uy5ELkIuLCBBLkUuSy4sIFQuRS5DLiwgVC5QLlIuLCBXLkwuTS4sIFMuQi4sIEQuRS5TLikmI3hB
O0Zyb20gdGhlIFN0YW5mb3JkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIFBhbG8gQWx0bywg
Q0EgKE0uQy5HLik7IEFsYmFueSBNZWRpY2FsIENvbGxlZ2UsIEFsYmFueSwgTlkgKCBKLksuKTsg
UmhldW1hemVudHJ1bSBGYXZvcml0ZW4gKE8uWi4pIGFuZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5
IG9mIFZpZW5uYSAoIEouUy5TLikgLSBib3RoIGluIFZpZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRv
bG9neSwgQmV0aGxlaGVtLCBQQSAoQy5MLik7IFJoZXVtYXRvbG9neSBDbGluaWMsIE1BSy1NRUQs
IE5hZGFyenluLCBQb2xhbmQgKE0uSy4pOyBhbmQgRWxpIExpbGx5LCBJbmRpYW5hcG9saXMgKEwu
WC4sIFMuRC5CLiwgQS5FLksuLCBULkUuQy4sIFQuUC5SLiwgVy5MLk0uLCBTLkIuLCBELkUuUy4p
JiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFs
dG8sIENBIChNLkMuRy4pOyBBbGJhbnkgTWVkaWNhbCBDb2xsZWdlLCBBbGJhbnksIE5ZICggSi5L
Lik7IFJoZXVtYXplbnRydW0gRmF2b3JpdGVuIChPLlouKSBhbmQgdGhlIE1lZGljYWwgVW5pdmVy
c2l0eSBvZiBWaWVubmEgKCBKLlMuUy4pIC0gYm90aCBpbiBWaWVubmE7IEVhc3QgUGVubiBSaGV1
bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEgKEMuTC4pOyBSaGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUst
TUVELCBOYWRhcnp5biwgUG9sYW5kIChNLksuKTsgYW5kIEVsaSBMaWxseSwgSW5kaWFuYXBvbGlz
IChMLlguLCBTLkQuQi4sIEEuRS5LLiwgVC5FLkMuLCBULlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5F
LlMuKSYjeEE7RnJvbSB0aGUgU3RhbmZvcmQgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgUGFs
byBBbHRvLCBDQSAoTS5DLkcuKTsgQWxiYW55IE1lZGljYWwgQ29sbGVnZSwgQWxiYW55LCBOWSAo
IEouSy4pOyBSaGV1bWF6ZW50cnVtIEZhdm9yaXRlbiAoTy5aLikgYW5kIHRoZSBNZWRpY2FsIFVu
aXZlcnNpdHkgb2YgVmllbm5hICggSi5TLlMuKSAtIGJvdGggaW4gVmllbm5hOyBFYXN0IFBlbm4g
UmhldW1hdG9sb2d5LCBCZXRobGVoZW0sIFBBIChDLkwuKTsgUmhldW1hdG9sb2d5IENsaW5pYywg
TUFLLU1FRCwgTmFkYXJ6eW4sIFBvbGFuZCAoTS5LLik7IGFuZCBFbGkgTGlsbHksIEluZGlhbmFw
b2xpcyAoTC5YLiwgUy5ELkIuLCBBLkUuSy4sIFQuRS5DLiwgVC5QLlIuLCBXLkwuTS4sIFMuQi4s
IEQuRS5TLikmI3hBO0Zyb20gdGhlIFN0YW5mb3JkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIs
IFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7IEFsYmFueSBNZWRpY2FsIENvbGxlZ2UsIEFsYmFueSwg
TlkgKCBKLksuKTsgUmhldW1hemVudHJ1bSBGYXZvcml0ZW4gKE8uWi4pIGFuZCB0aGUgTWVkaWNh
bCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAoIEouUy5TLikgLSBib3RoIGluIFZpZW5uYTsgRWFzdCBQ
ZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxlaGVtLCBQQSAoQy5MLik7IFJoZXVtYXRvbG9neSBDbGlu
aWMsIE1BSy1NRUQsIE5hZGFyenluLCBQb2xhbmQgKE0uSy4pOyBhbmQgRWxpIExpbGx5LCBJbmRp
YW5hcG9saXMgKEwuWC4sIFMuRC5CLiwgQS5FLksuLCBULkUuQy4sIFQuUC5SLiwgVy5MLk0uLCBT
LkIuLCBELkUuUy4pJiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2Vu
dGVyLCBQYWxvIEFsdG8sIENBIChNLkMuRy4pOyBBbGJhbnkgTWVkaWNhbCBDb2xsZWdlLCBBbGJh
bnksIE5ZICggSi5LLik7IFJoZXVtYXplbnRydW0gRmF2b3JpdGVuIChPLlouKSBhbmQgdGhlIE1l
ZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEgKCBKLlMuUy4pIC0gYm90aCBpbiBWaWVubmE7IEVh
c3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEgKEMuTC4pOyBSaGV1bWF0b2xvZ3kg
Q2xpbmljLCBNQUstTUVELCBOYWRhcnp5biwgUG9sYW5kIChNLksuKTsgYW5kIEVsaSBMaWxseSwg
SW5kaWFuYXBvbGlzIChMLlguLCBTLkQuQi4sIEEuRS5LLiwgVC5FLkMuLCBULlAuUi4sIFcuTC5N
LiwgUy5CLiwgRC5FLlMuKSYjeEE7RnJvbSB0aGUgU3RhbmZvcmQgVW5pdmVyc2l0eSBNZWRpY2Fs
IENlbnRlciwgUGFsbyBBbHRvLCBDQSAoTS5DLkcuKTsgQWxiYW55IE1lZGljYWwgQ29sbGVnZSwg
QWxiYW55LCBOWSAoIEouSy4pOyBSaGV1bWF6ZW50cnVtIEZhdm9yaXRlbiAoTy5aLikgYW5kIHRo
ZSBNZWRpY2FsIFVuaXZlcnNpdHkgb2YgVmllbm5hICggSi5TLlMuKSAtIGJvdGggaW4gVmllbm5h
OyBFYXN0IFBlbm4gUmhldW1hdG9sb2d5LCBCZXRobGVoZW0sIFBBIChDLkwuKTsgUmhldW1hdG9s
b2d5IENsaW5pYywgTUFLLU1FRCwgTmFkYXJ6eW4sIFBvbGFuZCAoTS5LLik7IGFuZCBFbGkgTGls
bHksIEluZGlhbmFwb2xpcyAoTC5YLiwgUy5ELkIuLCBBLkUuSy4sIFQuRS5DLiwgVC5QLlIuLCBX
LkwuTS4sIFMuQi4sIEQuRS5TLikmI3hBO0Zyb20gdGhlIFN0YW5mb3JkIFVuaXZlcnNpdHkgTWVk
aWNhbCBDZW50ZXIsIFBhbG8gQWx0bywgQ0EgKE0uQy5HLik7IEFsYmFueSBNZWRpY2FsIENvbGxl
Z2UsIEFsYmFueSwgTlkgKCBKLksuKTsgUmhldW1hemVudHJ1bSBGYXZvcml0ZW4gKE8uWi4pIGFu
ZCB0aGUgTWVkaWNhbCBVbml2ZXJzaXR5IG9mIFZpZW5uYSAoIEouUy5TLikgLSBib3RoIGluIFZp
ZW5uYTsgRWFzdCBQZW5uIFJoZXVtYXRvbG9neSwgQmV0aGxlaGVtLCBQQSAoQy5MLik7IFJoZXVt
YXRvbG9neSBDbGluaWMsIE1BSy1NRUQsIE5hZGFyenluLCBQb2xhbmQgKE0uSy4pOyBhbmQgRWxp
IExpbGx5LCBJbmRpYW5hcG9saXMgKEwuWC4sIFMuRC5CLiwgQS5FLksuLCBULkUuQy4sIFQuUC5S
LiwgVy5MLk0uLCBTLkIuLCBELkUuUy4pJiN4QTtGcm9tIHRoZSBTdGFuZm9yZCBVbml2ZXJzaXR5
IE1lZGljYWwgQ2VudGVyLCBQYWxvIEFsdG8sIENBIChNLkMuRy4pOyBBbGJhbnkgTWVkaWNhbCBD
b2xsZWdlLCBBbGJhbnksIE5ZICggSi5LLik7IFJoZXVtYXplbnRydW0gRmF2b3JpdGVuIChPLlou
KSBhbmQgdGhlIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEgKCBKLlMuUy4pIC0gYm90aCBp
biBWaWVubmE7IEVhc3QgUGVubiBSaGV1bWF0b2xvZ3ksIEJldGhsZWhlbSwgUEEgKEMuTC4pOyBS
aGV1bWF0b2xvZ3kgQ2xpbmljLCBNQUstTUVELCBOYWRhcnp5biwgUG9sYW5kIChNLksuKTsgYW5k
IEVsaSBMaWxseSwgSW5kaWFuYXBvbGlzIChMLlguLCBTLkQuQi4sIEEuRS5LLiwgVC5FLkMuLCBU
LlAuUi4sIFcuTC5NLiwgUy5CLiwgRC5FLlMuKTwvQWRkcmVzcz48V2ViX1VSTD5QTToyNzAyODkx
NDwvV2ViX1VSTD48WlpfSm91cm5hbFN0ZEFiYnJldj48ZiBuYW1lPSJTeXN0ZW0iPk4uRW5nbC5K
Lk1lZC48L2Y+PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtm
b3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRob3I+RmxlaXNjaG1hbm48L0F1dGhvcj48WWVh
cj4yMDEyPC9ZZWFyPjxSZWNOdW0+MjQ3MzwvUmVjTnVtPjxJRFRleHQ+UGxhY2Viby1jb250cm9s
bGVkIHRyaWFsIG9mIHRvZmFjaXRpbmliIG1vbm90aGVyYXB5IGluIHJoZXVtYXRvaWQgYXJ0aHJp
dGlzPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1Jl
Zl9UeXBlPjxSZWZfSUQ+MjQ3MzwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PlBsYWNlYm8tY29udHJv
bGxlZCB0cmlhbCBvZiB0b2ZhY2l0aW5pYiBtb25vdGhlcmFweSBpbiByaGV1bWF0b2lkIGFydGhy
aXRpczwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZsZWlzY2htYW5uLFIuPC9BdXRo
b3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LcmVtZXIsSi48L0F1dGhvcnNfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PkN1c2gsSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PlNjaHVsemUtS29vcHMsSC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkNvbm5l
bGwsQy5BLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QnJhZGxleSxKLkQuPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HcnViZW4sRC48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PldhbGxlbnN0ZWluLEcuVi48L0F1dGhvcnNfUHJpbWFyeT48QXV0
aG9yc19QcmltYXJ5Plp3aWxsaWNoLFMuSC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkthbmlrLEsuUy48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTIvOC85PC9E
YXRlX1ByaW1hcnk+PEtleXdvcmRzPkFjdGl2aXRpZXMgb2YgRGFpbHkgTGl2aW5nPC9LZXl3b3Jk
cz48S2V5d29yZHM+QWR1bHQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5hZHZlcnNlIGVmZmVjdHM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5hbnRhZ29uaXN0cyAmYW1wOyBpbmhpYml0b3JzPC9LZXl3b3Jkcz48
S2V5d29yZHM+QW50aXJoZXVtYXRpYyBBZ2VudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0
aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXMsUmhldW1hdG9pZDwvS2V5d29yZHM+PEtl
eXdvcmRzPkNob2xlc3Rlcm9sPC9LZXl3b3Jkcz48S2V5d29yZHM+RGlzYWJpbGl0eSBFdmFsdWF0
aW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRzPkRvdWJs
ZS1CbGluZCBNZXRob2Q8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRz
PjxLZXl3b3Jkcz5Fbnp5bWUgSW5oaWJpdG9yczwvS2V5d29yZHM+PEtleXdvcmRzPkZlbWFsZTwv
S2V5d29yZHM+PEtleXdvcmRzPkhlYWRhY2hlPC9LZXl3b3Jkcz48S2V5d29yZHM+SGVhbHRoPC9L
ZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+aW1tdW5vbG9neTwv
S2V5d29yZHM+PEtleXdvcmRzPkluZmVjdGlvbjwvS2V5d29yZHM+PEtleXdvcmRzPkphbnVzIEtp
bmFzZSAzPC9LZXl3b3Jkcz48S2V5d29yZHM+TGVhc3QtU3F1YXJlcyBBbmFseXNpczwvS2V5d29y
ZHM+PEtleXdvcmRzPkxldWtvY3l0ZSBDb3VudDwvS2V5d29yZHM+PEtleXdvcmRzPk1hbGU8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWlkZGxlIEFnZWQ8
L0tleXdvcmRzPjxLZXl3b3Jkcz5NdWx0aWNlbnRlciBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5d29y
ZHM+TmV1dHJvcGhpbHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtl
eXdvcmRzPlB5cmltaWRpbmVzPC9LZXl3b3Jkcz48S2V5d29yZHM+UHlycm9sZXM8L0tleXdvcmRz
PjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5
d29yZHM+PEtleXdvcmRzPlNldmVyaXR5IG9mIElsbG5lc3MgSW5kZXg8L0tleXdvcmRzPjxLZXl3
b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5PC9LZXl3b3Jk
cz48S2V5d29yZHM+VHJlYXRtZW50IE91dGNvbWU8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBG
aWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjQ5NTwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+NTA3PC9F
bmRfUGFnZT48UGVyaW9kaWNhbD5OLkVuZ2wuSi5NZWQuPC9QZXJpb2RpY2FsPjxWb2x1bWU+MzY3
PC9Wb2x1bWU+PElzc3VlPjY8L0lzc3VlPjxNaXNjXzM+MTAuMTA1Ni9ORUpNb2ExMTA5MDcxIFtk
b2ldPC9NaXNjXzM+PEFkZHJlc3M+TWV0cm9wbGV4IENsaW5pY2FsIFJlc2VhcmNoIENlbnRlciwg
RGFsbGFzLCBUWCA3NTIzMSwgVVNBLiByZmxlaXNjaG1hbm5AYXJ0aGRvY3MuY29tPC9BZGRyZXNz
PjxXZWJfVVJMPlBNOjIyODczNTMwPC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5h
bWU9IlN5c3RlbSI+Ti5FbmdsLkouTWVkLjwvZj48L1paX0pvdXJuYWxTdGRBYmJyZXY+PFpaX1dv
cmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5GbGVp
c2NobWFubjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051bT4yODM5PC9SZWNOdW0+PElE
VGV4dD5Ib3cgbXVjaCBkb2VzIERpc2Vhc2UgQWN0aXZpdHkgU2NvcmUgaW4gMjggam9pbnRzIEVT
UiBhbmQgQ1JQIGNhbGN1bGF0aW9ucyB1bmRlcmVzdGltYXRlIGRpc2Vhc2UgYWN0aXZpdHkgY29t
cGFyZWQgd2l0aCB0aGUgU2ltcGxpZmllZCBEaXNlYXNlIEFjdGl2aXR5IEluZGV4PzwvSURUZXh0
PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVm
X0lEPjI4Mzk8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5Ib3cgbXVjaCBkb2VzIERpc2Vhc2UgQWN0
aXZpdHkgU2NvcmUgaW4gMjggam9pbnRzIEVTUiBhbmQgQ1JQIGNhbGN1bGF0aW9ucyB1bmRlcmVz
dGltYXRlIGRpc2Vhc2UgYWN0aXZpdHkgY29tcGFyZWQgd2l0aCB0aGUgU2ltcGxpZmllZCBEaXNl
YXNlIEFjdGl2aXR5IEluZGV4PzwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZsZWlz
Y2htYW5uLFIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52YW4gZGVyIEhlaWpk
ZSxELjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S29lbmlnLEEuUy48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlBlZGVyc2VuLFIuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5TenVtc2tpLEEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5NYXJzaGFsbCxMLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QmFuYW5p
cyxFLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxNC84LzIwPC9EYXRlX1ByaW1h
cnk+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVhY3RpdmUgUHJv
dGVpbjwvS2V5d29yZHM+PEtleXdvcmRzPkNsaW5pY2FsIFRyaWFsczwvS2V5d29yZHM+PEtleXdv
cmRzPkRpc2Vhc2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5Kb2ludHM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+TmV0aGVybGFuZHM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlBlbm5zeWx2YW5pYTwvS2V5d29yZHM+
PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3
b3Jkcz48S2V5d29yZHM+VGV4YXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXBy
aW50PjxQZXJpb2RpY2FsPkFubiBSaGV1bSBEaXM8L1BlcmlvZGljYWw+PE1pc2NfMz5hbm5yaGV1
bWRpcy0yMDEzLTIwNDkyMCBbcGlpXTsxMC4xMTM2L2FubnJoZXVtZGlzLTIwMTMtMjA0OTIwIFtk
b2ldPC9NaXNjXzM+PEFkZHJlc3M+TWV0cm9wbGV4IENsaW5pY2FsIFJlc2VhcmNoIENlbnRlciwg
VW5pdmVyc2l0eSBvZiBUZXhhcyBTb3V0aHdlc3Rlcm4gTWVkaWNhbCBDZW50ZXIsIERhbGxhcywg
VGV4YXMsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIExlaWRlbiBVbml2ZXJz
aXR5IE1lZGljYWwgQ2VudGVyLCBMZWlkZW4sIFRoZSBOZXRoZXJsYW5kcyYjeEE7RGVwYXJ0bWVu
dCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIEluYywgQ29sbGVnZXZpbGxlLCBQZW5uc3lsdmFu
aWEsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIEluYywgQ29s
bGVnZXZpbGxlLCBQZW5uc3lsdmFuaWEsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBTcGVjaWFsdHkg
Q2FyZSwgUGZpemVyIEluYywgQ29sbGVnZXZpbGxlLCBQZW5uc3lsdmFuaWEsIFVTQSYjeEE7RGVw
YXJ0bWVudCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIEluYywgQ29sbGVnZXZpbGxlLCBQZW5u
c3lsdmFuaWEsIFVTQSYjeEE7RGVwYXJ0bWVudCBvZiBTcGVjaWFsdHkgQ2FyZSwgUGZpemVyIElu
YywgQ29sbGVnZXZpbGxlLCBQZW5uc3lsdmFuaWEsIFVTQTwvQWRkcmVzcz48V2ViX1VSTD5QTToy
NTE0MzUyMjwvV2ViX1VSTD48WlpfSm91cm5hbEZ1bGw+PGYgbmFtZT0iU3lzdGVtIj5Bbm4gUmhl
dW0gRGlzPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1J
RD48L01ETD48L0NpdGU+PC9SZWZtYW4+
ADDIN EN.CITE.DATA 92;95;96 It is important that the target-state should be sustained. The term “sustained” is still not defined precisely, and different studies have used different definitions, but some voices in the Task Force suggested at least 6 months as a minimal time frame. This requires follow-up and a strategy to adapt therapy intensity up- or downward, aspects that are dealt with in subsequent recommendations. However, treatment intensification must take patient factors into consideration, especially risks and comorbidities (overarching principle B) . This recommendation addresses two treatment targets: Remission, especially in DMARD-na?ve patients, and low disease activity, primarily in patients who failed previous therapies. Since clinical remission or low disease activity are mentioned as the sole therapeutic targets, any higher disease activity state has to be regarded as inadequate disease control, thus mandating a therapeutic change, obviously unless patient factors preclude this.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN EN.CITE.DATA 15 LoE 1a; LoA 9.6 Monitoring should be frequent in active disease (every 1–3 months); if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted. This recommendation on treat-to-target is unchanged in position and formulation from the 2013 version. The frequencies of follow-up examinations should be adjusted in accordance with the level of disease activity, namely more frequently, such as monthly, when patients have high disease activity, and less frequently, such as every 6 to 12 months when the treatment target has been attained and sustained. EULAR generally recommends the use of a composite measures of disease activity that include joint counts and the ACR-EULAR criteria for remission.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA 22;97 Improvement by 3 months refers to the fact that if a minimal change is not achieved, there is only a low likelihood of reaching the treatment target. Thus, a change to a better disease activity state should be seen at 3 months or a relative improvement, pertaining to at least a 30-50% improvement in activity by composite score, at that point in time, in order to have a considerable chance of reaching the target .PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGE8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGE8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS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ADDIN EN.CITE.DATA 31;88;98;99 Of note, adjustment of therapy includes the optimization of MTX (or other csDMARD) dose, ADDIN REFMGR.CITE <Refman><Cite><Author>Visser</Author><Year>2009</Year><RecNum>1521</RecNum><IDText>Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>1521</Ref_ID><Title_Primary>Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature</Title_Primary><Authors_Primary>Visser,K.</Authors_Primary><Authors_Primary>van der Heijde D.</Authors_Primary><Date_Primary>2009/7</Date_Primary><Keywords>administration & dosage</Keywords><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Drug Administration Routes</Keywords><Keywords>Drug Administration Schedule</Keywords><Keywords>drug therapy</Keywords><Keywords>Humans</Keywords><Keywords>methods</Keywords><Keywords>Methotrexate</Keywords><Keywords>Netherlands</Keywords><Keywords>Odds Ratio</Keywords><Keywords>Patients</Keywords><Keywords>Randomized Controlled Trials as Topic</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>toxicity</Keywords><Reprint>Not in File</Reprint><Start_Page>1094</Start_Page><End_Page>1099</End_Page><Periodical>Ann.Rheum Dis.</Periodical><Volume>68</Volume><Issue>7</Issue><Address>Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. K.Visser@lumc.nl</Address><Web_URL>PM:19033290</Web_URL><ZZ_JournalStdAbbrev><f name="System">Ann.Rheum Dis.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>4 or intraarticular injections of glucocorticoids in the presence of one or few residual active joints, and refers to a change of drugs only if these measures have not been successful or are not appropriate. Further, in an individual patient the treatment target may not have been fully achieved yet at 6 months. But if disease activity is close to the target, one may considering continuing the effective therapy for a few more weeks to make a final judgment, especially since a considerable proportion of patients may attain the target at a slightly later time point than at 6 months.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
Y051bT4zMDU4PC9SZWNOdW0+PElEVGV4dD5BdHRhaW5tZW50IGFuZCBjaGFyYWN0ZXJpc3RpY3Mg
b2YgY2xpbmljYWwgcmVtaXNzaW9uIGFjY29yZGluZyB0byB0aGUgbmV3IEFDUi1FVUxBUiBjcml0
ZXJpYSBpbiBhYmF0YWNlcHQtdHJlYXRlZCBwYXRpZW50cyB3aXRoIGVhcmx5IHJoZXVtYXRvaWQg
YXJ0aHJpdGlzOiBuZXcgYW5hbHlzZXMgZnJvbSB0aGUgQWJhdGFjZXB0IHN0dWR5IHRvIEdhdWdl
IFJlbWlzc2lvbiBhbmQgam9pbnQgZGFtYWdlIHByb2dyZXNzaW9uIGluIG1ldGhvdHJleGF0ZSAo
TVRYKS1uYWl2ZSBwYXRpZW50cyB3aXRoIGVhcmx5IGVyb3NpdmUgcmhldW1hdG9pZCBhcnRocml0
aXMgKEFHUkVFKTwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3Vy
bmFsPC9SZWZfVHlwZT48UmVmX0lEPjMwNTg8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5BdHRhaW5t
ZW50IGFuZCBjaGFyYWN0ZXJpc3RpY3Mgb2YgY2xpbmljYWwgcmVtaXNzaW9uIGFjY29yZGluZyB0
byB0aGUgbmV3IEFDUi1FVUxBUiBjcml0ZXJpYSBpbiBhYmF0YWNlcHQtdHJlYXRlZCBwYXRpZW50
cyB3aXRoIGVhcmx5IHJoZXVtYXRvaWQgYXJ0aHJpdGlzOiBuZXcgYW5hbHlzZXMgZnJvbSB0aGUg
QWJhdGFjZXB0IHN0dWR5IHRvIEdhdWdlIFJlbWlzc2lvbiBhbmQgam9pbnQgZGFtYWdlIHByb2dy
ZXNzaW9uIGluIG1ldGhvdHJleGF0ZSAoTVRYKS1uYWl2ZSBwYXRpZW50cyB3aXRoIGVhcmx5IGVy
b3NpdmUgcmhldW1hdG9pZCBhcnRocml0aXMgKEFHUkVFKTwvVGl0bGVfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PlNtb2xlbixKLlMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5X
b2xsZW5oYXVwdCxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+R29tZXotUmVp
bm8sSi5KLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+R3Jhc3NpLFcuPC9BdXRo
b3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HYWlsbGV6LEMuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5Qb25jZXQsQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkxlLEJhcnMgTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pldlc3Rob3Zl
bnMsUi48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTU8L0RhdGVfUHJpbWFyeT48
S2V5d29yZHM+QWJhdGFjZXB0PC9LZXl3b3Jkcz48S2V5d29yZHM+YWRtaW5pc3RyYXRpb24gJmFt
cDsgZG9zYWdlPC9LZXl3b3Jkcz48S2V5d29yZHM+QWR1bHQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5B
bnRpcmhldW1hdGljIEFnZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29y
ZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+QXVz
dHJpYTwvS2V5d29yZHM+PEtleXdvcmRzPmRpYWdub3NpczwvS2V5d29yZHM+PEtleXdvcmRzPkRp
c2Vhc2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5EaXNlYXNlIFByb2dyZXNzaW9uPC9LZXl3b3Jkcz48
S2V5d29yZHM+RG91YmxlLUJsaW5kIE1ldGhvZDwvS2V5d29yZHM+PEtleXdvcmRzPmRydWcgdGhl
cmFweTwvS2V5d29yZHM+PEtleXdvcmRzPkRydWcgVGhlcmFweSxDb21iaW5hdGlvbjwvS2V5d29y
ZHM+PEtleXdvcmRzPkZlbWFsZTwvS2V5d29yZHM+PEtleXdvcmRzPkZyYW5jZTwvS2V5d29yZHM+
PEtleXdvcmRzPkdlcm1hbnk8L0tleXdvcmRzPjxLZXl3b3Jkcz5IZWFsdGg8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5Ib3NwaXRhbHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1hbnM8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5JdGFseTwvS2V5d29yZHM+PEtleXdvcmRzPk1hbGU8L0tleXdvcmRzPjxLZXl3b3Jk
cz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWV0aG90cmV4YXRlPC9LZXl3b3Jkcz48S2V5
d29yZHM+TWlkZGxlIEFnZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+
PEtleXdvcmRzPlByb2JhYmlsaXR5PC9LZXl3b3Jkcz48S2V5d29yZHM+UmVtaXNzaW9uIEluZHVj
dGlvbjwvS2V5d29yZHM+PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+Umhl
dW1hdG9sb2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+U3BhaW48L0tleXdvcmRzPjxLZXl3b3Jkcz5U
aW1lPC9LZXl3b3Jkcz48S2V5d29yZHM+VHJlYXRtZW50IE91dGNvbWU8L0tleXdvcmRzPjxSZXBy
aW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjE1NzwvU3RhcnRfUGFnZT48UGVy
aW9kaWNhbD5BcnRocml0aXMgUmVzLlRoZXIuPC9QZXJpb2RpY2FsPjxWb2x1bWU+MTc8L1ZvbHVt
ZT48VXNlcl9EZWZfNT5QTUM0NDk0NzAyPC9Vc2VyX0RlZl81PjxNaXNjXzM+MTAuMTE4Ni9zMTMw
NzUtMDE1LTA2NzEtOSBbZG9pXTsxMC4xMTg2L3MxMzA3NS0wMTUtMDY3MS05IFtwaWldPC9NaXNj
XzM+PEFkZHJlc3M+RGl2aXNpb24gb2YgUmhldW1hdG9sb2d5LCBEZXBhcnRtZW50IG9mIE1lZGlj
aW5lIDMsIE1lZGljYWwgVW5pdmVyc2l0eSBvZiBWaWVubmEsIGFuZCAybmQgRGVwYXJ0bWVudCBv
ZiBNZWRpY2luZSwgSGlldHppbmcgSG9zcGl0YWwsIFdhZWhyaW5nZXIgR3VlcnRlbCAxOC0yMCwg
Vmllbm5hLCBBLTEwOTAsIEF1c3RyaWEuIGpvc2VmLnNtb2xlbkB3aWVua2F2LmF0JiN4QTtTY2hv
bi1LbGluaWssIEhhbWJ1cmctRWlsYmVrLCBIYW1idXJnLCBHZXJtYW55LiB3b2xsZW5oYXVwdEBy
aGV1bWF0b2xvZ2lrdW0uZGUmI3hBO0hvc3BpdGFsIENsaW5pY28gVW5pdmVyc2l0YXJpbywgU2Fu
dGlhZ28gZGUgQ29tcG9zdGVsYSwgU3BhaW4uIGp1YW4uamVzdXMuZ29tZXotcmVpbm8uY2Fybm90
YUBzZXJnYXMuZXMmI3hBO0NsaW5pY2EgUmV1bWF0b2xvZ2ljYSwgVW5pdmVyc2l0YSBQb2xpdGVj
bmljYSBkZWxsZSBNYXJjaGUsIEFuY29uYSwgSXRhbHkuIHdhbHRlcl9ncmFzc2lAeWFob28uaXQm
I3hBO0JyaXN0b2wtTXllcnMgU3F1aWJiLCBSdWVpbC1NYWxtYWlzb24sIEZyYW5jZS4gY29yaW5l
X2dhaWxsZXpAaG90bWFpbC5jb20mI3hBO0RvY3MgSW50ZXJuYXRpb25hbCwgTmFudGVycmUsIEZy
YW5jZS4gcG9uY2V0LmNvcmFsaWVAZ21haWwuY29tJiN4QTtCcmlzdG9sLU15ZXJzIFNxdWliYiwg
UnVlaWwtTWFsbWFpc29uLCBGcmFuY2UuIG1hbnVlbGEubGViYXJzQGJtcy5jb20mI3hBO1NrZWxl
dGFsIEJpb2xvZ3kgYW5kIEVuZ2luZWVyaW5nIFJlc2VhcmNoIENlbnRlciwgRGVwYXJ0bWVudCBv
ZiBEZXZlbG9wbWVudCBhbmQgUmVnZW5lcmF0aW9uIEtVIExldXZlbjsgUmhldW1hdG9sb2d5LCBV
bml2ZXJzaXR5IEhvc3BpdGFscyBMZXV2ZW4sIExldXZlbiwgQmVsZ2l1bTwvQWRkcmVzcz48V2Vi
X1VSTD5QTToyNjA2MzQ1NDwvV2ViX1VSTD48WlpfSm91cm5hbFN0ZEFiYnJldj48ZiBuYW1lPSJT
eXN0ZW0iPkFydGhyaXRpcyBSZXMuVGhlci48L2Y+PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9X
b3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRob3I+TGk8
L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNOdW0+MzEzMjwvUmVjTnVtPjxJRFRleHQ+SGln
aCByZW1pc3Npb24gYW5kIGxvdyByZWxhcHNlIHdpdGggcHJvbG9uZ2VkIGludGVuc2l2ZSBETUFS
RCB0aGVyYXB5IGluIHJoZXVtYXRvaWQgYXJ0aHJpdGlzIChQUklOVCk6IEEgbXVsdGljZW50ZXIg
cmFuZG9taXplZCBjbGluaWNhbCB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwi
PjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjMxMzI8L1JlZl9JRD48VGl0bGVf
UHJpbWFyeT5IaWdoIHJlbWlzc2lvbiBhbmQgbG93IHJlbGFwc2Ugd2l0aCBwcm9sb25nZWQgaW50
ZW5zaXZlIERNQVJEIHRoZXJhcHkgaW4gcmhldW1hdG9pZCBhcnRocml0aXMgKFBSSU5UKTogQSBt
dWx0aWNlbnRlciByYW5kb21pemVkIGNsaW5pY2FsIHRyaWFsPC9UaXRsZV9QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+TGksUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlpoYW8s
Si5YLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3UsWS48L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PkhlLEouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5DaGVuLEwuTi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pkd1LEYuPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5aaGFvLEMuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5EZW5nLFguUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5Plpob3UsVy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkhhbyxZLkouPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5YdWUsWS48L0F1dGhvcnNfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PkxpdSxILlguPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5aaGFvLFkuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5ab3UsUS5ILjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGl1LFguWS48L0F1dGhvcnNfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PlpodSxQLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
U3VuLEwuWS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlpoYW5nLFouTC48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlpvdSxILkouPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5MaSxYLkYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5MaXUsWS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkZhbmcsWS5GLjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2V5c3RvbmUsRS48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5Pk1jSW5uZXMsSS5CLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+TGksWi5HLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxNi83PC9E
YXRlX1ByaW1hcnk+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkF1dG9p
bW11bmUgRGlzZWFzZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5DYW5hZGE8L0tleXdvcmRzPjxLZXl3
b3Jkcz5DaGluYTwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vhc2U8L0tleXdvcmRzPjxLZXl3b3Jk
cz5IZWFsdGg8L0tleXdvcmRzPjxLZXl3b3Jkcz5IeWRyb3h5Y2hsb3JvcXVpbmU8L0tleXdvcmRz
PjxLZXl3b3Jkcz5JbW11bml0eTwvS2V5d29yZHM+PEtleXdvcmRzPmltbXVub2xvZ3k8L0tleXdv
cmRzPjxLZXl3b3Jkcz5JbmZlY3Rpb248L0tleXdvcmRzPjxLZXl3b3Jkcz5JbmZsYW1tYXRpb248
L0tleXdvcmRzPjxLZXl3b3Jkcz5Kb2ludHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+TWV0aG90cmV4YXRlPC9LZXl3b3Jkcz48S2V5d29yZHM+UGF0aWVu
dHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaGV1bWF0b2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz50
aGVyYXB5PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFn
ZT5lMzk2ODwvU3RhcnRfUGFnZT48UGVyaW9kaWNhbD5NZWRpY2luZSAoQmFsdGltb3JlKTwvUGVy
aW9kaWNhbD48Vm9sdW1lPjk1PC9Wb2x1bWU+PElzc3VlPjI4PC9Jc3N1ZT48VXNlcl9EZWZfNT5Q
TUM0OTU2NzgwPC9Vc2VyX0RlZl81PjxNaXNjXzM+MTAuMTA5Ny9NRC4wMDAwMDAwMDAwMDAzOTY4
IFtkb2ldOzAwMDA1NzkyLTIwMTYwNzEyMC0wMDAwOCBbcGlpXTwvTWlzY18zPjxBZGRyZXNzPmFE
ZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSBhbmQgSW1tdW5vbG9neSwgUGVraW5nIFVuaXZlcnNp
dHkgUGVvcGxlJmFwb3M7cyBIb3NwaXRhbCBiRGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3kgYW5k
IEltbXVub2xvZ3ksIFBla2luZyBVbml2ZXJzaXR5IFRoaXJkIEhvc3BpdGFsLCBCZWlqaW5nIGNE
ZXBhcnRtZW50IG9mIENsaW5pY2FsIEltbXVub2xvZ3ksIEZvdXJ0aCBNaWxpdGFyeSBNZWRpY2Fs
IFVuaXZlcnNpdHkgWGlqaW5nIEhvc3BpdGFsLCBYaSZhcG9zO2FuIGREZXBhcnRtZW50IG9mIFJo
ZXVtYXRvbG9neSBhbmQgSW1tdW5vbG9neSwgVGhlIEFmZmlsaWF0ZWQgRHJ1bSBUb3dlciBIb3Nw
aXRhbCBvZiBOYW5qaW5nIFVuaXZlcnNpdHkgTWVkaWNhbCBTY2hvb2wsIE5hbmppbmcgZURlcGFy
dG1lbnQgb2YgUmhldW1hdG9sb2d5IGFuZCBDbGluaWNhbCBJbW11bm9sb2d5LCBQZWtpbmcgVW5p
dmVyc2l0eSBGaXJzdCBIb3NwaXRhbCwgQmVpamluZyBmRGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xv
Z3kgYW5kIEltbXVub2xvZ3ksIEZ1ZGFuIFVuaXZlcnNpdHkgSHVhc2hhbiBIb3NwaXRhbCwgU2hh
bmdoYWkgZ0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5IGFuZCBJbW11bm9sb2d5LCBTaGFuZG9u
ZyBVbml2ZXJzaXR5IFFpbHUgSG9zcGl0YWwsIEppbmFuIGhEZXBhcnRtZW50IG9mIFJoZXVtYXRv
bG9neSBhbmQgSW1tdW5vbG9neSwgU2ljaHVhbiBVbml2ZXJzaXR5IFdlc3QgQ2hpbmEgSG9zcGl0
YWwsIENoZW5nZHUgaURlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5IGFuZCBJbW11bm9sb2d5LCBU
aGlyZCBNaWxpdGFyeSBNZWRpY2FsIFVuaXZlcnNpdHkgU291dGh3ZXN0IEhvc3BpdGFsLCBDaG9u
Z3FpbmcsIENoaW5hIGpUaGUgUmViZWNjYSBNYWNEb25hbGQgQ2VudHJlIGZvciBBcnRocml0aXMg
YW5kIEF1dG9pbW11bmUgRGlzZWFzZXMsIE1vdW50IFNpbmFpIEhvc3BpdGFsLCBVbml2ZXJzaXR5
IG9mIFRvcm9udG8sIFRvcm9udG8sIENhbmFkYSBrSW5zdGl0dXRlIG9mIEluZmVjdGlvbiwgSW1t
dW5pdHkgYW5kIEluZmxhbW1hdGlvbiwgQ29sbGVnZSBvZiBNZWRpY2FsLCBWZXRlcmluYXJ5IGFu
ZCBMaWZlIFNjaWVuY2VzLCBVbml2ZXJzaXR5IG9mIEdsYXNnb3csIEdsYXNnb3csIFVLPC9BZGRy
ZXNzPjxXZWJfVVJMPlBNOjI3NDI4MTg2PC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2Pjxm
IG5hbWU9IlN5c3RlbSI+TWVkaWNpbmUgKEJhbHRpbW9yZSk8L2Y+PC9aWl9Kb3VybmFsU3RkQWJi
cmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjwvUmVmbWFu
Pm==
ADDIN EN.CITE.DATA 100;101 Consequently, the change in disease activity from baseline, and its slope should be considered when making treatment decisions. LoE 2b; LoA 9.5MTX should be part of the first treatment strategy. Compared with 2013, when this item read “MTX should be part of the first treatment strategy in patients with active RA”, the recommendation was slightly shortened. The Task Force felt that pointing to active disease was not necessary, since the EULAR recommendations primarily address patients with active disease. Based on its efficacy, safety (especially in the presence of folic acid), the possibility to individualize dose and method of administration as well as relatively low costs, MTX continues to be the anchor (“first”) drug for patients with RA both as monotherapy as well as in combination with other drugs (“treatment strategy”; see below). Moreover, MTX appears to reduce comorbidities and mortality in RA.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNob2k8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFyPjxSZWNO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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNob2k8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA 102;103 In clinical trials of biological agents in early arthritis patients MTX-monotherapy had been associated with 25% ACR70 response rates (which brings patients into the range of low disease activity) within 6 months, even though it had not been combined with de novo glucocorticoids in these trials. ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen</Author><Year>2015</Year><RecNum>3054</RecNum><IDText>Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3054</Ref_ID><Title_Primary>Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges</Title_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Date_Primary>2015/5</Date_Primary><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Austria</Keywords><Keywords>Biological Factors</Keywords><Keywords>Chronic Disease</Keywords><Keywords>Disease</Keywords><Keywords>Disease Progression</Keywords><Keywords>drug therapy</Keywords><Keywords>history</Keywords><Keywords>Humans</Keywords><Keywords>methods</Keywords><Keywords>Molecular Targeted Therapy</Keywords><Keywords>Patients</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>therapeutic use</Keywords><Keywords>therapy</Keywords><Keywords>Treatment Outcome</Keywords><Reprint>Not in File</Reprint><Start_Page>276</Start_Page><End_Page>289</End_Page><Periodical>Nat.Rev.Rheumatol</Periodical><Volume>11</Volume><Issue>5</Issue><Misc_3>nrrheum.2015.8 [pii];10.1038/nrrheum.2015.8 [doi]</Misc_3><Address>Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria</Address><Web_URL>PM:25687177</Web_URL><ZZ_JournalStdAbbrev><f name="System">Nat.Rev.Rheumatol</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>78 MTX should be rapidly escalated, usually to 25-30mg/week, orally or subcutaneously administered, with folic acid supplementation ADDIN REFMGR.CITE <Refman><Cite><Author>Visser</Author><Year>2009</Year><RecNum>1521</RecNum><IDText>Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>1521</Ref_ID><Title_Primary>Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature</Title_Primary><Authors_Primary>Visser,K.</Authors_Primary><Authors_Primary>van der Heijde D.</Authors_Primary><Date_Primary>2009/7</Date_Primary><Keywords>administration & dosage</Keywords><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Drug Administration Routes</Keywords><Keywords>Drug Administration Schedule</Keywords><Keywords>drug therapy</Keywords><Keywords>Humans</Keywords><Keywords>methods</Keywords><Keywords>Methotrexate</Keywords><Keywords>Netherlands</Keywords><Keywords>Odds Ratio</Keywords><Keywords>Patients</Keywords><Keywords>Randomized Controlled Trials as Topic</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>toxicity</Keywords><Reprint>Not in File</Reprint><Start_Page>1094</Start_Page><End_Page>1099</End_Page><Periodical>Ann.Rheum Dis.</Periodical><Volume>68</Volume><Issue>7</Issue><Address>Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. K.Visser@lumc.nl</Address><Web_URL>PM:19033290</Web_URL><ZZ_JournalStdAbbrev><f name="System">Ann.Rheum Dis.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>4 and the maximal MTX dose, if tolerated, should be sustained for about 8-12 weeks to judge the MTX treatment response. Indeed, when MTX is rapidly escalated to 25mg per week, the response rate may even be higher (~40% low disease activity).PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkVtZXJ5PC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkVtZXJ5PC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 104 Of course, contraindications and the potential of early toxicity have to be taken into account; this is addressed in item 5. The doses mentioned here do not pertain to Asian patients. In China, it is not recommended to exceed 20mg/weekPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxpPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVjTnVt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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxpPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVjTnVt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ADDIN EN.CITE.DATA 101 and in Japan the maximum recommended dose for MTX is 16mg/week.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkF0c3VtaTwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkF0c3VtaTwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN EN.CITE.DATA 105Of note, at this point in time the Task Force decided to delete previous recommendation 6 (“In DMARD-na?ve patients, irrespective of the addition of glucocorticoids, csDMARD monotherapy or combination therapy of csDMARDs should be used”). The inclusion or exclusion of combinations of csDMARDs within the bullet points elicited long debates within the respective breakout group and the whole Task Force (and the withdrawal of one Task Force member). The first ballot of the Task Force involved a choice of the following two wordings: (a) “MTX should be part of the first treatment strategy” and (b) “In DMARD-na?ve patients, irrespective of the addition of glucocorticoids, csDMARD monotherapy or combination therapy of csDMARDs should be used” (identical with the respective 2013 recommendation) with 23 votes favoring (a), 22 votes favoring (b) and 1 abstention. Therefore further discussions took place. Advocates in favor of including combination therapy referred to publications suggesting its superior efficacy compared with csDMARD monotherapy and similar efficacy compared with biological agents;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1vdHRvbmVuPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1vdHRvbmVuPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48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ADDIN EN.CITE.DATA 106-110 moreover, in some countries, such as Finland, csDMARD combination therapy is recommended by the national societies as preferred initial therapy. Other Task Force members.pointed to trials that did not show a real benefit of combination therapy (especially when in the comparator arms csDMARD monotherapy was combined with glucocorticoids);PFJlZm1hbj48Q2l0ZT48QXV0aG9yPmRlIEpvbmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPmRlIEpvbmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
ZWNOdW0+MjgwNjwvUmVjTnVtPjxJRFRleHQ+UmFuZG9taXNlZCBjb21wYXJpc29uIG9mIGluaXRp
YWwgdHJpcGxlIERNQVJEIHRoZXJhcHkgd2l0aCBtZXRob3RyZXhhdGUgbW9ub3RoZXJhcHkgaW4g
Y29tYmluYXRpb24gd2l0aCBsb3ctZG9zZSBnbHVjb2NvcnRpY29pZCBicmlkZ2luZyB0aGVyYXB5
OyAxLXllYXIgZGF0YSBvZiB0aGUgdFJFQUNIIHRyaWFsPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0i
Sm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MjgwNjwvUmVmX0lE
PjxUaXRsZV9QcmltYXJ5PlJhbmRvbWlzZWQgY29tcGFyaXNvbiBvZiBpbml0aWFsIHRyaXBsZSBE
TUFSRCB0aGVyYXB5IHdpdGggbWV0aG90cmV4YXRlIG1vbm90aGVyYXB5IGluIGNvbWJpbmF0aW9u
IHdpdGggbG93LWRvc2UgZ2x1Y29jb3J0aWNvaWQgYnJpZGdpbmcgdGhlcmFweTsgMS15ZWFyIGRh
dGEgb2YgdGhlIHRSRUFDSCB0cmlhbDwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRl
IEpvbmcsUC5ILjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF6ZXMsSi5NLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SGFuLEguSy48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5Pkh1aXNtYW4sTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PnZhbixaZWJlbiBELjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFu
IGRlciBMdWJiZSxQLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HZXJhcmRz
LEEuSC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbixTY2hhZXlicm9lY2sg
Qi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlIFNvbm5hdmlsbGUsUC5CLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIEtydWd0ZW4sTS5WLjwvQXV0aG9y
c19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+THVpbWUsSi5KLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+V2VlbCxBLkUuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4y
MDE0Lzc8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QXJtPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0
aHJpdGlzPC9LZXl3b3Jkcz48S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRzPmRy
dWcgdGhlcmFweTwvS2V5d29yZHM+PEtleXdvcmRzPkhlYWx0aDwvS2V5d29yZHM+PEtleXdvcmRz
Pm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3
b3Jkcz5OZXRoZXJsYW5kczwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48
S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFweTwvS2V5d29y
ZHM+PEtleXdvcmRzPlRpbWU8L0tleXdvcmRzPjxLZXl3b3Jkcz5UcmVhdG1lbnQgRmFpbHVyZTwv
S2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+MTMzMTwv
U3RhcnRfUGFnZT48RW5kX1BhZ2U+MTMzOTwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QW5uIFJoZXVt
IERpczwvUGVyaW9kaWNhbD48Vm9sdW1lPjczPC9Wb2x1bWU+PElzc3VlPjc8L0lzc3VlPjxNaXNj
XzM+YW5ucmhldW1kaXMtMjAxMy0yMDQ3ODggW3BpaV07MTAuMTEzNi9hbm5yaGV1bWRpcy0yMDEz
LTIwNDc4OCBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPkRlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5
LCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBSb3R0ZXJkYW0sIFRoZSBOZXRoZXJsYW5kcyYj
eEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIs
IFJvdHRlcmRhbSwgVGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9n
eSwgTWFhc3N0YWQgSG9zcGl0YWwsIFJvdHRlcmRhbSwgVGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBh
cnRtZW50IG9mIFJoZXVtYXRvbG9neSwgU2ludCBGcmFuY2ljdXMgR2FzdGh1aXMgSG9zcGl0YWws
IFJvdHRlcmRhbSwgVGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9n
eSwgU2ludCBGcmFuY2ljdXMgR2FzdGh1aXMgSG9zcGl0YWwsIFJvdHRlcmRhbSwgVGhlIE5ldGhl
cmxhbmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgVmxpZXRsYW5kIEhvc3BpdGFs
LCBTY2hpZWRhbSwgVGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9n
eSwgVmxpZXRsYW5kIEhvc3BpdGFsLCBTY2hpZWRhbSwgVGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBh
cnRtZW50IG9mIFJoZXVtYXRvbG9neSwgQWxiZXJ0IFNjaHdlaXR6ZXIgSG9zcGl0YWwsIERvcmRy
ZWNodCwgVGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgQWRt
aXJhYWwgZGUgUnV5dGVyIEhvc3BpdGFsLCBHb2VzICZhbXA7IFZsaXNzaW5nZW4sIFRoZSBOZXRo
ZXJsYW5kcyYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIEFkbWlyYWFsIGRlIFJ1eXRl
ciBIb3NwaXRhbCwgR29lcyAmYW1wOyBWbGlzc2luZ2VuLCBUaGUgTmV0aGVybGFuZHMmI3hBO0Rl
cGFydG1lbnQgb2YgUmhldW1hdG9sb2d5LCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBSb3R0
ZXJkYW0sIFRoZSBOZXRoZXJsYW5kcyYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFVu
aXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIFJvdHRlcmRhbSwgVGhlIE5ldGhlcmxhbmRzIERlcGFy
dG1lbnQgb2YgUmhldW1hdG9sb2d5LCBNYWFzc3RhZCBIb3NwaXRhbCwgUm90dGVyZGFtLCBUaGUg
TmV0aGVybGFuZHM8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjQ3ODg2MTk8L1dlYl9VUkw+PFpaX0pv
dXJuYWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+QW5uIFJoZXVtIERpczwvZj48L1paX0pvdXJuYWxG
dWxsPjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxB
dXRob3I+VmVyc2NodWVyZW48L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxSZWNOdW0+MjkwNTwv
UmVjTnVtPjxJRFRleHQ+TWV0aG90cmV4YXRlIGluIGNvbWJpbmF0aW9uIHdpdGggb3RoZXIgRE1B
UkRzIGlzIG5vdCBzdXBlcmlvciB0byBtZXRob3RyZXhhdGUgYWxvbmUgZm9yIHJlbWlzc2lvbiBp
bmR1Y3Rpb24gd2l0aCBtb2RlcmF0ZS10by1oaWdoLWRvc2UgZ2x1Y29jb3J0aWNvaWQgYnJpZGdp
bmcgaW4gZWFybHkgcmhldW1hdG9pZCBhcnRocml0aXMgYWZ0ZXIgMTYgd2Vla3Mgb2YgdHJlYXRt
ZW50OiB0aGUgQ2FyZVJBIHRyaWFsPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJl
Zl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MjkwNTwvUmVmX0lEPjxUaXRsZV9Qcmlt
YXJ5Pk1ldGhvdHJleGF0ZSBpbiBjb21iaW5hdGlvbiB3aXRoIG90aGVyIERNQVJEcyBpcyBub3Qg
c3VwZXJpb3IgdG8gbWV0aG90cmV4YXRlIGFsb25lIGZvciByZW1pc3Npb24gaW5kdWN0aW9uIHdp
dGggbW9kZXJhdGUtdG8taGlnaC1kb3NlIGdsdWNvY29ydGljb2lkIGJyaWRnaW5nIGluIGVhcmx5
IHJoZXVtYXRvaWQgYXJ0aHJpdGlzIGFmdGVyIDE2IHdlZWtzIG9mIHRyZWF0bWVudDogdGhlIENh
cmVSQSB0cmlhbDwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlZlcnNjaHVlcmVuLFAu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EZSxDb2NrIEQuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Db3JsdXksTC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5Pkpvb3MsUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pkxhbmdl
bmFrZW4sQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlRhZWxtYW4sVi48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlJhZW1hbixGLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+UmF2ZWxpbmdpZW4sSS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PlZhbmRldnl2ZXJlLEsuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5MZW5hZXJ0cyxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+R2VlbnMsRS48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkdldXNlbnMsUC48L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PlZhbmhvb2YsSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkR1cm5leixBLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UmVt
YW5zLEouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5WYW5kZXIsQ3J1eXNzZW4g
Qi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlZhbixFc3NjaGUgRS48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNpbGVnaGVtLEEuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5EZSxCcmFiYW50ZXIgRy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkpvbHksSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1leWZy
b2lkdCxTLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+VmFuIGRlciBFbHN0LEsu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5XZXN0aG92ZW5zLFIuPC9BdXRob3Jz
X1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDE1LzE8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QWR1
bHQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5BZ2VkPC9LZXl3b3Jkcz48S2V5d29yZHM+YW5hbHlzaXM8
L0tleXdvcmRzPjxLZXl3b3Jkcz5BbnRpcmhldW1hdGljIEFnZW50czwvS2V5d29yZHM+PEtleXdv
cmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9L
ZXl3b3Jkcz48S2V5d29yZHM+Qy1SZWFjdGl2ZSBQcm90ZWluPC9LZXl3b3Jkcz48S2V5d29yZHM+
ZGlhZ25vc2lzPC9LZXl3b3Jkcz48S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRz
PmRydWcgdGhlcmFweTwvS2V5d29yZHM+PEtleXdvcmRzPkRydWcgVGhlcmFweSxDb21iaW5hdGlv
bjwvS2V5d29yZHM+PEtleXdvcmRzPkVhcmx5IE1lZGljYWwgSW50ZXJ2ZW50aW9uPC9LZXl3b3Jk
cz48S2V5d29yZHM+RmVtYWxlPC9LZXl3b3Jkcz48S2V5d29yZHM+R2x1Y29jb3J0aWNvaWRzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+SGVhbHRoPC9LZXl3b3Jkcz48S2V5d29yZHM+SG9zcGl0YWxzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+SW5kdWN0aW9uIENo
ZW1vdGhlcmFweTwvS2V5d29yZHM+PEtleXdvcmRzPkludGVudGlvbiB0byBUcmVhdCBBbmFseXNp
czwvS2V5d29yZHM+PEtleXdvcmRzPklzb3hhem9sZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NYWxl
PC9LZXl3b3Jkcz48S2V5d29yZHM+bWV0aG9kczwvS2V5d29yZHM+PEtleXdvcmRzPk1ldGhvdHJl
eGF0ZTwvS2V5d29yZHM+PEtleXdvcmRzPk1pZGRsZSBBZ2VkPC9LZXl3b3Jkcz48S2V5d29yZHM+
TmV0aGVybGFuZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdv
cmRzPlByZWRuaXNvbmU8L0tleXdvcmRzPjxLZXl3b3Jkcz5QdWJsaWMgSGVhbHRoPC9LZXl3b3Jk
cz48S2V5d29yZHM+UmVtaXNzaW9uIEluZHVjdGlvbjwvS2V5d29yZHM+PEtleXdvcmRzPlJlc2Vh
cmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+
UmlzazwvS2V5d29yZHM+PEtleXdvcmRzPlJpc2sgQXNzZXNzbWVudDwvS2V5d29yZHM+PEtleXdv
cmRzPlNhZmV0eTwvS2V5d29yZHM+PEtleXdvcmRzPnNlY29uZGFyeTwvS2V5d29yZHM+PEtleXdv
cmRzPlNldmVyaXR5IG9mIElsbG5lc3MgSW5kZXg8L0tleXdvcmRzPjxLZXl3b3Jkcz5TdWxmYXNh
bGF6aW5lPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFwZXV0aWMgdXNlPC9LZXl3b3Jkcz48S2V5
d29yZHM+dGhlcmFweTwvS2V5d29yZHM+PEtleXdvcmRzPlRyZWF0bWVudCBPdXRjb21lPC9LZXl3
b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4yNzwvU3RhcnRf
UGFnZT48RW5kX1BhZ2U+MzQ8L0VuZF9QYWdlPjxQZXJpb2RpY2FsPkFubiBSaGV1bSBEaXM8L1Bl
cmlvZGljYWw+PFZvbHVtZT43NDwvVm9sdW1lPjxJc3N1ZT4xPC9Jc3N1ZT48TWlzY18zPmFubnJo
ZXVtZGlzLTIwMTQtMjA1NDg5IFtwaWldOzEwLjExMzYvYW5ucmhldW1kaXMtMjAxNC0yMDU0ODkg
W2RvaV08L01pc2NfMz48QWRkcmVzcz5Ta2VsZXRhbCBCaW9sb2d5IGFuZCBFbmdpbmVlcmluZyBS
ZXNlYXJjaCBDZW50ZXIsIEtVIExldXZlbiBEZXBhcnRtZW50IG9mIERldmVsb3BtZW50IGFuZCBS
ZWdlbmVyYXRpb24sIExldXZlbiwgQmVsZ2l1bSBEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwg
VW5pdmVyc2l0eSBIb3NwaXRhbHMgTGV1dmVuLCBMZXV2ZW4sIEJlbGdpdW0mI3hBO1NrZWxldGFs
IEJpb2xvZ3kgYW5kIEVuZ2luZWVyaW5nIFJlc2VhcmNoIENlbnRlciwgS1UgTGV1dmVuIERlcGFy
dG1lbnQgb2YgRGV2ZWxvcG1lbnQgYW5kIFJlZ2VuZXJhdGlvbiwgTGV1dmVuLCBCZWxnaXVtJiN4
QTtSZXVtYS1pbnN0aXR1dXQgSGFzc2VsdCwgSGFzc2VsdCwgQmVsZ2l1bSBKZXNzYSBaaWVrZW5o
dWlzIEhhc3NlbHQsIEhhc3NlbHQsIEJlbGdpdW0mI3hBO1pOQSBKYW4gUGFsZmlqbiBBbnR3ZXJw
ZW4sIEFudHdlcnBlbiwgQmVsZ2l1bSYjeEE7UmV1bWEtaW5zdGl0dXV0IEhhc3NlbHQsIEhhc3Nl
bHQsIEJlbGdpdW0gSmVzc2EgWmlla2VuaHVpcyBIYXNzZWx0LCBIYXNzZWx0LCBCZWxnaXVtJiN4
QTtIZWlsaWcgSGFydCBaaWVrZW5odWlzIExldXZlbiwgTGV1dmVuLCBCZWxnaXVtJiN4QTtaTkEg
SmFuIFBhbGZpam4gQW50d2VycGVuLCBBbnR3ZXJwZW4sIEJlbGdpdW0mI3hBO0RlcGFydG1lbnQg
b2YgUmhldW1hdG9sb2d5LCBPbnplLUxpZXZlLVZyb3V3IFppZWtlbmh1aXMgQWFsc3QsIEFhbHN0
LCBCZWxnaXVtJiN4QTtBWiBHcm9lbmluZ2UgSG9zcGl0YWwgS29ydHJpamssIEtvcnRyaWprLCBC
ZWxnaXVtJiN4QTtSZXVtYS1pbnN0aXR1dXQgSGFzc2VsdCwgSGFzc2VsdCwgQmVsZ2l1bSBKZXNz
YSBaaWVrZW5odWlzIEhhc3NlbHQsIEhhc3NlbHQsIEJlbGdpdW0mI3hBO1pOQSBKYW4gUGFsZmlq
biBBbnR3ZXJwZW4sIEFudHdlcnBlbiwgQmVsZ2l1bSYjeEE7UmV1bWFDbGluaWMgR2VuayAmYW1w
OyBVSGFzc2VsdCwgSGFzc2VsdCwgQmVsZ2l1bSBNYWFzdHJpY2h0IFVNQywgTWFhc3RyaWNodCwg
dGhlIE5ldGhlcmxhbmRzJiN4QTtSZXVtYUNsaW5pYyBHZW5rICZhbXA7IFVIYXNzZWx0LCBIYXNz
ZWx0LCBCZWxnaXVtJiN4QTtBWiBHcm9lbmluZ2UgSG9zcGl0YWwgS29ydHJpamssIEtvcnRyaWpr
LCBCZWxnaXVtJiN4QTtSZXVtYS1pbnN0aXR1dXQgR2VuaywgR2VuaywgQmVsZ2l1bSYjeEE7RGVw
YXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIE9uemUtTGlldmUtVnJvdXcgWmlla2VuaHVpcyBBYWxz
dCwgQWFsc3QsIEJlbGdpdW0mI3hBO0ltZWxkYXppZWtlbmh1aXMgQm9uaGVpZGVuLCBCb25oZWlk
ZW4sIEJlbGdpdW0mI3hBO1JldW1hQ2xpbmljIEhhc3NlbHQsIEhhc3NlbHQsIEJlbGdpdW0mI3hB
O0FaIFNpbnQgTHVjYXMgQnJ1Z2dlLCBCcnVnZ2UsIEJlbGdpdW0mI3hBO0RlcGFydG1lbnQgb2Yg
UmhldW1hdG9sb2d5LCBVbml2ZXJzaXR5IEhvc3BpdGFscyBMZXV2ZW4sIExldXZlbiwgQmVsZ2l1
bSYjeEE7U2tlbGV0YWwgQmlvbG9neSBhbmQgRW5naW5lZXJpbmcgUmVzZWFyY2ggQ2VudGVyLCBL
VSBMZXV2ZW4gRGVwYXJ0bWVudCBvZiBEZXZlbG9wbWVudCBhbmQgUmVnZW5lcmF0aW9uLCBMZXV2
ZW4sIEJlbGdpdW0mI3hBO0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5LCBVbml2ZXJzaXR5IEhv
c3BpdGFscyBMZXV2ZW4sIExldXZlbiwgQmVsZ2l1bSBTa2VsZXRhbCBCaW9sb2d5IGFuZCBFbmdp
bmVlcmluZyBSZXNlYXJjaCBDZW50ZXIsIEtVIExldXZlbiBEZXBhcnRtZW50IG9mIFB1YmxpYyBI
ZWFsdGggYW5kIFByaW1hcnkgQ2FyZSwgTGV1dmVuLCBCZWxnaXVtJiN4QTtTa2VsZXRhbCBCaW9s
b2d5IGFuZCBFbmdpbmVlcmluZyBSZXNlYXJjaCBDZW50ZXIsIEtVIExldXZlbiBEZXBhcnRtZW50
IG9mIERldmVsb3BtZW50IGFuZCBSZWdlbmVyYXRpb24sIExldXZlbiwgQmVsZ2l1bSBEZXBhcnRt
ZW50IG9mIFJoZXVtYXRvbG9neSwgVW5pdmVyc2l0eSBIb3NwaXRhbHMgTGV1dmVuLCBMZXV2ZW4s
IEJlbGdpdW08L0FkZHJlc3M+PFdlYl9VUkw+UE06MjUzNTkzODI8L1dlYl9VUkw+PFpaX0pvdXJu
YWxGdWxsPjxmIG5hbWU9IlN5c3RlbSI+QW5uIFJoZXVtIERpczwvZj48L1paX0pvdXJuYWxGdWxs
PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRo
b3I+R29la29vcC1SdWl0ZXJtYW48L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxSZWNOdW0+MTI1
MTwvUmVjTnVtPjxJRFRleHQ+Q29tcGFyaXNvbiBvZiB0cmVhdG1lbnQgc3RyYXRlZ2llcyBpbiBl
YXJseSByaGV1bWF0b2lkIGFydGhyaXRpczogYSByYW5kb21pemVkIHRyaWFsPC9JRFRleHQ+PE1E
TCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+
MTI1MTwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PkNvbXBhcmlzb24gb2YgdHJlYXRtZW50IHN0cmF0
ZWdpZXMgaW4gZWFybHkgcmhldW1hdG9pZCBhcnRocml0aXM6IGEgcmFuZG9taXplZCB0cmlhbDwv
VGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkdvZWtvb3AtUnVpdGVybWFuLFkuUC48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlIFZyaWVzLUJvdXdzdHJhLEouSy48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFsbGFhcnQsQy5GLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuLFplYmVuIEQuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5LZXJzdGVucyxQLkouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5IYXplcyxKLk0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5ad2luZGVybWFu
LEEuSC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlBlZXRlcnMsQS5KLjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+ZGUgSm9uZ2UtQm9rLEouTS48L0F1dGhvcnNf
UHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1hbGxlZSxDLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+ZGUgQmV1cyxXLk0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5kZSBTb25uYXZpbGxlLFAuQi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkV3
YWxzLEouQS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJyZWVkdmVsZCxGLkMu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EaWprbWFucyxCLkEuPC9BdXRob3Jz
X1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDA3LzMvMjA8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+
YWR2ZXJzZSBlZmZlY3RzPC9LZXl3b3Jkcz48S2V5d29yZHM+QW50aS1JbmZsYW1tYXRvcnkgQWdl
bnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+QW50aWJvZGllczwvS2V5d29yZHM+PEtleXdvcmRzPkFu
dGlib2RpZXMsTW9ub2Nsb25hbDwvS2V5d29yZHM+PEtleXdvcmRzPkFudGlyaGV1bWF0aWMgQWdl
bnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJpdGlzPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0
aHJpdGlzLFJoZXVtYXRvaWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5Db21wYXJhdGl2ZSBTdHVkeTwv
S2V5d29yZHM+PEtleXdvcmRzPkRydWcgQWRtaW5pc3RyYXRpb24gU2NoZWR1bGU8L0tleXdvcmRz
PjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5EcnVnIFRoZXJhcHks
Q29tYmluYXRpb248L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1hbnM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5NdWx0aWNlbnRlciBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5d29yZHM+UGF0aWVudHM8L0tleXdv
cmRzPjxLZXl3b3Jkcz5QcmVkbmlzb25lPC9LZXl3b3Jkcz48S2V5d29yZHM+cmFkaW9ncmFwaHk8
L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRv
bG9neTwvS2V5d29yZHM+PEtleXdvcmRzPlNpbmdsZS1CbGluZCBNZXRob2Q8L0tleXdvcmRzPjxL
ZXl3b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5PC9LZXl3
b3Jkcz48S2V5d29yZHM+dG94aWNpdHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5UcmVhdG1lbnQgT3V0
Y29tZTwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+
NDA2PC9TdGFydF9QYWdlPjxFbmRfUGFnZT40MTU8L0VuZF9QYWdlPjxQZXJpb2RpY2FsPkFubiBJ
bnRlcm4uTWVkLjwvUGVyaW9kaWNhbD48Vm9sdW1lPjE0NjwvVm9sdW1lPjxJc3N1ZT42PC9Jc3N1
ZT48QWRkcmVzcz5EZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgTGVpZGVuIFVuaXZlcnNpdHkg
TWVkaWNhbCBDZW50ZXIsIExlaWRlbiwgVGhlIE5ldGhlcmxhbmRzLiB5LnAubS5nb2Vrb29wQGx1
bWMubmw8L0FkZHJlc3M+PFdlYl9VUkw+UE06MTczNzE4ODU8L1dlYl9VUkw+PFpaX0pvdXJuYWxT
dGRBYmJyZXY+PGYgbmFtZT0iU3lzdGVtIj5Bbm4gSW50ZXJuLk1lZC48L2Y+PC9aWl9Kb3VybmFs
U3RkQWJicmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjwv
UmVmbWFuPgB=
ADDIN EN.CITE.DATA 111-113 differences in glucocorticoid co-intervention between combination- and monotherapy arms in previous trials; ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen JS</Author><Year>2005</Year><RecNum>871</RecNum><IDText>Superior efficacy of combination therapy for rheumatoid arthritis. Fact or Fiction?</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>871</Ref_ID><Title_Primary>Superior efficacy of combination therapy for rheumatoid arthritis. Fact or Fiction?</Title_Primary><Authors_Primary>Smolen JS</Authors_Primary><Authors_Primary>Aletaha D</Authors_Primary><Authors_Primary>Keystone E</Authors_Primary><Date_Primary>2005</Date_Primary><Keywords>therapy</Keywords><Keywords>Arthritis</Keywords><Reprint>In File</Reprint><Start_Page>2975</Start_Page><End_Page>2983</End_Page><Periodical>Arthritis Rheum</Periodical><Volume>52</Volume><ZZ_JournalFull><f name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>114 issues concerning the design of some investigator initiated trials suggesting superiority of csDMARD combinations;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxhbmRld2U8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxhbmRld2U8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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ADDIN EN.CITE.DATA 115 the significantly higher rate of profound responses upon combination with bDMARDs compared with the combination with csDMARD therapy after insufficient response to MTX;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk8mYXBvcztEZWxsPC9BdXRob3I+PFllYXI+MjAxMzwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk8mYXBvcztEZWxsPC9BdXRob3I+PFllYXI+MjAxMzwvWWVh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ADDIN EN.CITE.DATA 109 and the higher level of toxicity of csDMARD combinations versus monotherapy.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh
cj48UmVjTnVtPjI5MDU8L1JlY051bT48SURUZXh0Pk1ldGhvdHJleGF0ZSBpbiBjb21iaW5hdGlv
biB3aXRoIG90aGVyIERNQVJEcyBpcyBub3Qgc3VwZXJpb3IgdG8gbWV0aG90cmV4YXRlIGFsb25l
IGZvciByZW1pc3Npb24gaW5kdWN0aW9uIHdpdGggbW9kZXJhdGUtdG8taGlnaC1kb3NlIGdsdWNv
Y29ydGljb2lkIGJyaWRnaW5nIGluIGVhcmx5IHJoZXVtYXRvaWQgYXJ0aHJpdGlzIGFmdGVyIDE2
IHdlZWtzIG9mIHRyZWF0bWVudDogdGhlIENhcmVSQSB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5
cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlwZT48UmVmX0lEPjI5MDU8L1Jl
Zl9JRD48VGl0bGVfUHJpbWFyeT5NZXRob3RyZXhhdGUgaW4gY29tYmluYXRpb24gd2l0aCBvdGhl
ciBETUFSRHMgaXMgbm90IHN1cGVyaW9yIHRvIG1ldGhvdHJleGF0ZSBhbG9uZSBmb3IgcmVtaXNz
aW9uIGluZHVjdGlvbiB3aXRoIG1vZGVyYXRlLXRvLWhpZ2gtZG9zZSBnbHVjb2NvcnRpY29pZCBi
cmlkZ2luZyBpbiBlYXJseSByaGV1bWF0b2lkIGFydGhyaXRpcyBhZnRlciAxNiB3ZWVrcyBvZiB0
cmVhdG1lbnQ6IHRoZSBDYXJlUkEgdHJpYWw8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5WZXJzY2h1ZXJlbixQLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RGUsQ29j
ayBELjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q29ybHV5LEwuPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Kb29zLFIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5MYW5nZW5ha2VuLEMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5UYWVsbWFuLFYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5SYWVtYW4sRi48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlJhdmVsaW5naWVuLEkuPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5WYW5kZXZ5dmVyZSxLLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+TGVuYWVydHMsSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PkdlZW5zLEUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HZXVzZW5z
LFAuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5WYW5ob29mLEouPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EdXJuZXosQS48L0F1dGhvcnNfUHJpbWFyeT48QXV0
aG9yc19QcmltYXJ5PlJlbWFucyxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
VmFuZGVyLENydXlzc2VuIEIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5WYW4s
RXNzY2hlIEUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TaWxlZ2hlbSxBLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RGUsQnJhYmFudGVyIEcuPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Kb2x5LEouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5NZXlmcm9pZHQsUy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PlZhbiBkZXIgRWxzdCxLLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V2VzdGhv
dmVucyxSLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxNS8xPC9EYXRlX1ByaW1h
cnk+PEtleXdvcmRzPkFkdWx0PC9LZXl3b3Jkcz48S2V5d29yZHM+QWdlZDwvS2V5d29yZHM+PEtl
eXdvcmRzPmFuYWx5c2lzPC9LZXl3b3Jkcz48S2V5d29yZHM+QW50aXJoZXVtYXRpYyBBZ2VudHM8
L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0
aXMsUmhldW1hdG9pZDwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVhY3RpdmUgUHJvdGVpbjwvS2V5
d29yZHM+PEtleXdvcmRzPmRpYWdub3NpczwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vhc2U8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5EcnVnIFRo
ZXJhcHksQ29tYmluYXRpb248L0tleXdvcmRzPjxLZXl3b3Jkcz5FYXJseSBNZWRpY2FsIEludGVy
dmVudGlvbjwvS2V5d29yZHM+PEtleXdvcmRzPkZlbWFsZTwvS2V5d29yZHM+PEtleXdvcmRzPkds
dWNvY29ydGljb2lkczwvS2V5d29yZHM+PEtleXdvcmRzPkhlYWx0aDwvS2V5d29yZHM+PEtleXdv
cmRzPkhvc3BpdGFsczwvS2V5d29yZHM+PEtleXdvcmRzPkh1bWFuczwvS2V5d29yZHM+PEtleXdv
cmRzPkluZHVjdGlvbiBDaGVtb3RoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5JbnRlbnRpb24g
dG8gVHJlYXQgQW5hbHlzaXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Jc294YXpvbGVzPC9LZXl3b3Jk
cz48S2V5d29yZHM+TWFsZTwvS2V5d29yZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5NZXRob3RyZXhhdGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwvS2V5
d29yZHM+PEtleXdvcmRzPk5ldGhlcmxhbmRzPC9LZXl3b3Jkcz48S2V5d29yZHM+UGF0aWVudHM8
L0tleXdvcmRzPjxLZXl3b3Jkcz5QcmVkbmlzb25lPC9LZXl3b3Jkcz48S2V5d29yZHM+UHVibGlj
IEhlYWx0aDwvS2V5d29yZHM+PEtleXdvcmRzPlJlbWlzc2lvbiBJbmR1Y3Rpb248L0tleXdvcmRz
PjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5
d29yZHM+PEtleXdvcmRzPlJpc2s8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrIEFzc2Vzc21lbnQ8
L0tleXdvcmRzPjxLZXl3b3Jkcz5TYWZldHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5zZWNvbmRhcnk8
L0tleXdvcmRzPjxLZXl3b3Jkcz5TZXZlcml0eSBvZiBJbGxuZXNzIEluZGV4PC9LZXl3b3Jkcz48
S2V5d29yZHM+U3VsZmFzYWxhemluZTwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcGV1dGljIHVz
ZTwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5UcmVhdG1l
bnQgT3V0Y29tZTwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+PFN0YXJ0
X1BhZ2U+Mjc8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjM0PC9FbmRfUGFnZT48UGVyaW9kaWNhbD5B
bm4gUmhldW0gRGlzPC9QZXJpb2RpY2FsPjxWb2x1bWU+NzQ8L1ZvbHVtZT48SXNzdWU+MTwvSXNz
dWU+PE1pc2NfMz5hbm5yaGV1bWRpcy0yMDE0LTIwNTQ4OSBbcGlpXTsxMC4xMTM2L2FubnJoZXVt
ZGlzLTIwMTQtMjA1NDg5IFtkb2ldPC9NaXNjXzM+PEFkZHJlc3M+U2tlbGV0YWwgQmlvbG9neSBh
bmQgRW5naW5lZXJpbmcgUmVzZWFyY2ggQ2VudGVyLCBLVSBMZXV2ZW4gRGVwYXJ0bWVudCBvZiBE
ZXZlbG9wbWVudCBhbmQgUmVnZW5lcmF0aW9uLCBMZXV2ZW4sIEJlbGdpdW0gRGVwYXJ0bWVudCBv
ZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgSG9zcGl0YWxzIExldXZlbiwgTGV1dmVuLCBCZWxn
aXVtJiN4QTtTa2VsZXRhbCBCaW9sb2d5IGFuZCBFbmdpbmVlcmluZyBSZXNlYXJjaCBDZW50ZXIs
IEtVIExldXZlbiBEZXBhcnRtZW50IG9mIERldmVsb3BtZW50IGFuZCBSZWdlbmVyYXRpb24sIExl
dXZlbiwgQmVsZ2l1bSYjeEE7UmV1bWEtaW5zdGl0dXV0IEhhc3NlbHQsIEhhc3NlbHQsIEJlbGdp
dW0gSmVzc2EgWmlla2VuaHVpcyBIYXNzZWx0LCBIYXNzZWx0LCBCZWxnaXVtJiN4QTtaTkEgSmFu
IFBhbGZpam4gQW50d2VycGVuLCBBbnR3ZXJwZW4sIEJlbGdpdW0mI3hBO1JldW1hLWluc3RpdHV1
dCBIYXNzZWx0LCBIYXNzZWx0LCBCZWxnaXVtIEplc3NhIFppZWtlbmh1aXMgSGFzc2VsdCwgSGFz
c2VsdCwgQmVsZ2l1bSYjeEE7SGVpbGlnIEhhcnQgWmlla2VuaHVpcyBMZXV2ZW4sIExldXZlbiwg
QmVsZ2l1bSYjeEE7Wk5BIEphbiBQYWxmaWpuIEFudHdlcnBlbiwgQW50d2VycGVuLCBCZWxnaXVt
JiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgT256ZS1MaWV2ZS1Wcm91dyBaaWVrZW5o
dWlzIEFhbHN0LCBBYWxzdCwgQmVsZ2l1bSYjeEE7QVogR3JvZW5pbmdlIEhvc3BpdGFsIEtvcnRy
aWprLCBLb3J0cmlqaywgQmVsZ2l1bSYjeEE7UmV1bWEtaW5zdGl0dXV0IEhhc3NlbHQsIEhhc3Nl
bHQsIEJlbGdpdW0gSmVzc2EgWmlla2VuaHVpcyBIYXNzZWx0LCBIYXNzZWx0LCBCZWxnaXVtJiN4
QTtaTkEgSmFuIFBhbGZpam4gQW50d2VycGVuLCBBbnR3ZXJwZW4sIEJlbGdpdW0mI3hBO1JldW1h
Q2xpbmljIEdlbmsgJmFtcDsgVUhhc3NlbHQsIEhhc3NlbHQsIEJlbGdpdW0gTWFhc3RyaWNodCBV
TUMsIE1hYXN0cmljaHQsIHRoZSBOZXRoZXJsYW5kcyYjeEE7UmV1bWFDbGluaWMgR2VuayAmYW1w
OyBVSGFzc2VsdCwgSGFzc2VsdCwgQmVsZ2l1bSYjeEE7QVogR3JvZW5pbmdlIEhvc3BpdGFsIEtv
cnRyaWprLCBLb3J0cmlqaywgQmVsZ2l1bSYjeEE7UmV1bWEtaW5zdGl0dXV0IEdlbmssIEdlbmss
IEJlbGdpdW0mI3hBO0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5LCBPbnplLUxpZXZlLVZyb3V3
IFppZWtlbmh1aXMgQWFsc3QsIEFhbHN0LCBCZWxnaXVtJiN4QTtJbWVsZGF6aWVrZW5odWlzIEJv
bmhlaWRlbiwgQm9uaGVpZGVuLCBCZWxnaXVtJiN4QTtSZXVtYUNsaW5pYyBIYXNzZWx0LCBIYXNz
ZWx0LCBCZWxnaXVtJiN4QTtBWiBTaW50IEx1Y2FzIEJydWdnZSwgQnJ1Z2dlLCBCZWxnaXVtJiN4
QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgVW5pdmVyc2l0eSBIb3NwaXRhbHMgTGV1dmVu
LCBMZXV2ZW4sIEJlbGdpdW0mI3hBO1NrZWxldGFsIEJpb2xvZ3kgYW5kIEVuZ2luZWVyaW5nIFJl
c2VhcmNoIENlbnRlciwgS1UgTGV1dmVuIERlcGFydG1lbnQgb2YgRGV2ZWxvcG1lbnQgYW5kIFJl
Z2VuZXJhdGlvbiwgTGV1dmVuLCBCZWxnaXVtJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9n
eSwgVW5pdmVyc2l0eSBIb3NwaXRhbHMgTGV1dmVuLCBMZXV2ZW4sIEJlbGdpdW0gU2tlbGV0YWwg
QmlvbG9neSBhbmQgRW5naW5lZXJpbmcgUmVzZWFyY2ggQ2VudGVyLCBLVSBMZXV2ZW4gRGVwYXJ0
bWVudCBvZiBQdWJsaWMgSGVhbHRoIGFuZCBQcmltYXJ5IENhcmUsIExldXZlbiwgQmVsZ2l1bSYj
eEE7U2tlbGV0YWwgQmlvbG9neSBhbmQgRW5naW5lZXJpbmcgUmVzZWFyY2ggQ2VudGVyLCBLVSBM
ZXV2ZW4gRGVwYXJ0bWVudCBvZiBEZXZlbG9wbWVudCBhbmQgUmVnZW5lcmF0aW9uLCBMZXV2ZW4s
IEJlbGdpdW0gRGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgSG9zcGl0YWxz
IExldXZlbiwgTGV1dmVuLCBCZWxnaXVtPC9BZGRyZXNzPjxXZWJfVVJMPlBNOjI1MzU5MzgyPC9X
ZWJfVVJMPjxaWl9Kb3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFubiBSaGV1bSBEaXM8L2Y+
PC9aWl9Kb3VybmFsRnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwv
Q2l0ZT48L1JlZm1hbj5=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA 112 It was also argued that a higher prevelance of adverse events when using combination therapy, even though often mild, may preclude escalation of therapy and result in not reaching a full dose of some of the drugs. Also, the SLR on csDMARDs did not show evidence for superiority of csDMARD combinations compared with csDMARD monotherapy. ADDIN REFMGR.CITE <Refman><Cite><Author>Chatzidionysiou K</Author><Year>2016</Year><RecNum>3138</RecNum><IDText>SLR on csDMARDs to inform the EULAR RA management task force 2016</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3138</Ref_ID><Title_Primary>SLR on csDMARDs to inform the EULAR RA management task force 2016</Title_Primary><Authors_Primary>Chatzidionysiou K</Authors_Primary><Date_Primary>2016</Date_Primary><Reprint>Not in File</Reprint><Periodical>Ann Rheum Dis (submitted)</Periodical><ZZ_JournalFull><f name="System">Ann Rheum Dis (submitted)</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>50 Moreover, the ACR Committee on the 2015 update of the ACR management guideline, in contrast to previous versions,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNpbmdoPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNpbmdoPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 116 did not longer recommend csDMARD combination as initial therapy, but prioritized MTX monotherapy.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNpbmdoPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNpbmdoPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 17 In line, the updated EULAR recommendations for the management of early arthritis do not advocate the use of csDMARD combination therapy. ADDIN REFMGR.CITE <Refman><Cite><Author>Combe B</Author><Year>2016</Year><RecNum>3095</RecNum><IDText>2016 update of the EULAR recommendations for management of early arthritis.</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3095</Ref_ID><Title_Primary>2016 update of the EULAR recommendations for management of early arthritis.</Title_Primary><Authors_Primary>Combe B</Authors_Primary><Authors_Primary>et al</Authors_Primary><Date_Primary>2016</Date_Primary><Keywords>Arthritis</Keywords><Reprint>Not in File</Reprint><Periodical>Ann.Rheum Dis.</Periodical><Volume>submitted</Volume><ZZ_JournalStdAbbrev><f name="System">Ann.Rheum Dis.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>117 It was also pointed out that choice (a) included the term “treatment strategy” and thus comprised the option to use csDMARD combinations. These discussions resulted in a new ballot between two versions for recommendation 4: (a) “MTX should be part of the first treatment strategy” (as above); and (b) “MTX should be the first csDMARD, either as monotherapy or in combination with other csDMARDs”. In this 2nd ballot a 71% majority voted for version (a). Thus, csDMARD combination therapy is not longer mentioned explicitly as initial treatment suggestion within the abbreviated list of recommendations. It should be mentioned, though, that the simple fact that csDMARD combination therapy is not included in the bullet point anymore, does not preclude using it. This is obviously at the discretion of the physician and the patient together in light of all pros and cons that had been discussed (a ‘shared decision’). This recommendation ultimately attained a very high level of agreement (9.8). The Task Force was well aware that in some countries, such as in the UK or Canada, rheumatologists are required to use at least two csDMARDs before the application of bDMARDs is approved by the payers and that combinations of two or three csDMARDs are accepted in lieu of two csDMARD courses. However, for the reasons just mentioned, the Task Force was not in favour of the practice to define an insufficient response to a combination of csDMARDs as a failure of two or more csDMARDs (when in reality it constitutes only one therapeutic strategy) nor to preclude the approval of bDMARD use when a first csDMARD has failed and the patient has bad prognostic markers (see below item 8 and Table 1). LoE 1a; LoA 9.8In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the (first) treatment strategy. The contents of this recommendation were maintained; however, compared with the previous version of item 5, the wording “in cases of MTX contraindications” was slightly amended, because it is patients who have contraindications, rather than ‘cases’. The Task Force reiterated the relative safety of MTX and it was also discussed that the frequent fears of patients after reading the package insert should be addressed by providing appropriate information (overarching principle A). Nevertheless, there are occasional contraindications (e.g. kidney or liver) or intolerances. Under these circumstances, leflunomide (dosed at 20mg per day without loading dose)PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkN1dG9sbzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkN1dG9sbzwvQXV0aG9yPjxZZWFyPjIwMTM8L1llYXI+PFJl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 EN.CITE.DATA 118 or sulfasalazine (escalated to 3g per day) are regarded the best alternatives. Older trials have suggested similar efficacy for both these drugs compared with MTX, although MTX was used at much lower doses than recommended today.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdhdWpvdXgtVmlhbGEgQzwvQXV0aG9yPjxZZWFyPjIwMTA8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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdhdWpvdXgtVmlhbGEgQzwvQXV0aG9yPjxZZWFyPjIwMTA8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 EN.CITE.DATA 119;120 However, no new trials have been performed to disprove the previous conclusions. Among all the above agents, only sulfasalazine has an acceptable safety profile during pregnancy.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkfDtnRlc3RhbSBTa29ycGVuIEMuPC9BdXRob3I+PFllYXI+
MjAxNjwvWWVhcj48UmVjTnVtPjMwMDY8L1JlY051bT48SURUZXh0PlRoZSBFVUxBUiBwb2ludHMg
dG8gY29uc2lkZXIgZm9yIHVzZSBvZiBhbnRpcmhldW1hdGljIGRydWdzIGJlZm9yZSBwcmVnbmFu
Y3ksIGFuZCBkdXJpbmcgcHJlZ25hbmN5IGFuZCBsYWN0YXRpb248L0lEVGV4dD48TURMIFJlZl9U
eXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5cGU+PFJlZl9JRD4zMDA2PC9S
ZWZfSUQ+PFRpdGxlX1ByaW1hcnk+VGhlIEVVTEFSIHBvaW50cyB0byBjb25zaWRlciBmb3IgdXNl
IG9mIGFudGlyaGV1bWF0aWMgZHJ1Z3MgYmVmb3JlIHByZWduYW5jeSwgYW5kIGR1cmluZyBwcmVn
bmFuY3kgYW5kIGxhY3RhdGlvbjwvVGl0bGVfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkcmI3hG
Njt0ZXN0YW0gU2tvcnBlbiBDLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+SG9l
bHR6ZW5iZWluLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5UaW5jYW5pLEEu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5GaXNjaGVyLUJldHosUi48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkVsZWZhbnQsRS48L0F1dGhvcnNfUHJpbWFyeT48
QXV0aG9yc19QcmltYXJ5PkNoYW1iZXJzLEMuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5kYSxTaWx2YSBKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TmVsc29u
LVBpZXJjeSxDLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q2V0aW4sSS48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkNvc3RlZG9hdC1DaGFsdW1lYXUsTi48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkRvbGhhaW4sUi48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PkZvcmdlcixGLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1By
aW1hcnk+S2hhbWFzaHRhLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5SdWl6
LUlyYXN0b3J6YSxHLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+WmluayxBLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+VmVuY292c2t5LEouPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5DdXRvbG8sTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkNhZXllcnMsTi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Plp1
bWJ1aGwsQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk9zdGVuc2VuLE0uPC9B
dXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDE2LzIvMTc8L0RhdGVfUHJpbWFyeT48S2V5
d29yZHM+QWJhdGFjZXB0PC9LZXl3b3Jkcz48S2V5d29yZHM+QW50aW1hbGFyaWFsczwvS2V5d29y
ZHM+PEtleXdvcmRzPkF1dG9pbW11bmUgRGlzZWFzZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BemF0
aGlvcHJpbmU8L0tleXdvcmRzPjxLZXl3b3Jkcz5DYWxpZm9ybmlhPC9LZXl3b3Jkcz48S2V5d29y
ZHM+Q2hpbGQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5DeWNsb3Bob3NwaGFtaWRlPC9LZXl3b3Jkcz48
S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRzPkRvY3VtZW50YXRpb248L0tleXdv
cmRzPjxLZXl3b3Jkcz5lcGlkZW1pb2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5GcmFuY2U8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5HZXJtYW55PC9LZXl3b3Jkcz48S2V5d29yZHM+R2x1Y29jb3J0aWNv
aWRzPC9LZXl3b3Jkcz48S2V5d29yZHM+SGVhbHRoPC9LZXl3b3Jkcz48S2V5d29yZHM+aW1tdW5v
bG9neTwvS2V5d29yZHM+PEtleXdvcmRzPkl0YWx5PC9LZXl3b3Jkcz48S2V5d29yZHM+TGFjdGF0
aW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+TWV0aG90cmV4YXRlPC9LZXl3b3Jkcz48S2V5d29yZHM+
TmV0aGVybGFuZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Ob3J3YXk8L0tleXdvcmRzPjxLZXl3b3Jk
cz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlByZWduYW5jeTwvS2V5d29yZHM+PEtleXdv
cmRzPlJlZ2lzdHJpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtl
eXdvcmRzPlJoZXVtYXRpYyBEaXNlYXNlczwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9n
eTwvS2V5d29yZHM+PEtleXdvcmRzPlJpc2s8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrIEFzc2Vz
c21lbnQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXR1eGltYWI8L0tleXdvcmRzPjxLZXl3b3Jkcz5T
YWZldHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5TcGFpbjwvS2V5d29yZHM+PEtleXdvcmRzPlN1bGZh
c2FsYXppbmU8L0tleXdvcmRzPjxLZXl3b3Jkcz5Td2l0emVybGFuZDwvS2V5d29yZHM+PEtleXdv
cmRzPlRhY3JvbGltdXM8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxQ
ZXJpb2RpY2FsPkFubiBSaGV1bSBEaXM8L1BlcmlvZGljYWw+PFZvbHVtZT48ZiBuYW1lPSJUaW1l
cyBOZXcgUm9tYW4iPltFcHViIGFoZWFkIG9mIHByaW50XTwvZj48L1ZvbHVtZT48TWlzY18zPmFu
bnJoZXVtZGlzLTIwMTUtMjA4ODQwIFtwaWldOzEwLjExMzYvYW5ucmhldW1kaXMtMjAxNS0yMDg4
NDAgW2RvaV08L01pc2NfMz48QWRkcmVzcz5OYXRpb25hbCBTZXJ2aWNlIGZvciBQcmVnbmFuY3kg
YW5kIFJoZXVtYXRpYyBEaXNlYXNlcywgRGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFRyb25k
aGVpbSBVbml2ZXJzaXR5IEhvc3BpdGFsLCBUcm9uZGhlaW0sIE5vcndheSBEZXBhcnRtZW50IG9m
IE5ldXJvc2NpZW5jZSwgTm9yd2VnaWFuIFVuaXZlcnNpdHkgb2YgU2NpZW5jZSBhbmQgVGVjaG5v
bG9neSAoTlROVSksIFRyb25kaGVpbSwgTm9yd2F5IERlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5
LCBBbGVzdW5kIEhvc3BpdGFsLCBBbGVzdW5kLCBOb3J3YXkmI3hBO0JlcmxpbiBJbnN0aXR1dGUg
Zm9yIENsaW5pY2FsIFRlcmF0b2xvZ3kgYW5kIERydWcgUmlzayBBc3Nlc3NtZW50IGluIFByZWdu
YW5jeSwgQ2hhcml0ZS1Vbml2ZXJzaXRhdHNtZWRpemluIEJlcmxpbiwgQmVybGluLCBHZXJtYW55
JiN4QTtEZXBhcnRtZW50IG9mIENsaW5pY2FsIGFuZCBFeHBlcmltZW50YWwgU2NpZW5jZSBSaGV1
bWF0b2xvZ3kgYW5kIENsaW5pY2FsIEltbXVub2xvZ3kgVW5pdCwgU3BlZGFsaSBDaXZpbGkgYW5k
IFVuaXZlcnNpdHkgb2YgQnJlc2NpYSwgQnJlc2NpYSwgSXRhbHkmI3hBO0RlcGFydG1lbnQgb2Yg
UmhldW1hdG9sb2d5LCBVbml2ZXJzaXR5IEhvc3BpdGFsIG9mIER1c3NlbGRvcmYsIER1ZXNzZWxk
b3JmLCBHZXJtYW55JiN4QTtDZW50cmUgZGUgUmVmZXJlbmNlIHN1ciBsZXMgQWdlbnRzIFRlcmF0
b2dlbmVzIChDUkFUKSwgR3JvdXBlIEhvc3BpdGFsaWVyIFVuaXZlcnNpdGFpcmUgRXN0LCBIb3Bp
dGFsIEFybWFuZCBUcm91c3NlYXUsIFBhcmlzLCBGcmFuY2UmI3hBO0RlcGFydG1lbnQgb2YgUGVk
aWF0cmljcywgVW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhIFNhbiBEaWVnbywgTGEgSm9sbGEsIFVT
QSYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgSG9zcGl0YWwsIENv
aW1icmEsIFBvcnR1Z2FsJiN4QTtXb21lbiZhcG9zO3MgSGVhbHRoIEFjYWRlbWljIENlbnRyZSwg
U3QgVGhvbWFzJmFwb3M7IEhvc3BpdGFsLCBMb25kb24sIFVLJiN4QTtEZXBhcnRtZW50IG9mIE1v
dGhlciBhbmQgQ2hpbGQsIEhvc3BpdGFsIEx1aWdpIFNhY2NvLCBVbml2ZXJzaXR5IG9mIE1pbGFu
bywgTWlsYW5vLCBJdGFseSYjeEE7VW5pdmVyc2l0ZSBQYXJpcy1EZXNjYXJ0ZXMsIFBhcmlzLCBG
cmFuY2UgU2VydmljZSBkZSBtZWRlY2luZSBpbnRlcm5lLCBBUC1IUCwgSG9waXRhbCBDb2NoaW4s
IENlbnRyZSBkZSByZWZlcmVuY2UgbWFsYWRpZXMgYXV0by1pbW11bmVzIGV0IHN5c3RlbWlxdWVz
IHJhcmVzLCBQYXJpcywgRnJhbmNlJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgRXJh
c211cyBNQywgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciBSb3R0ZXJkYW0sIFJvdHRlcmRhbSwg
VGhlIE5ldGhlcmxhbmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgSW1tdW5vbG9n
eSBhbmQgQWxsZXJnb2xvZ3ksIFVuaXZlcnNpdHkgSG9zcGl0YWwgb2YgQmVybiwgQmVybiwgU3dp
dHplcmxhbmQmI3hBO0dyYWhhbSBIdWdoZXMgTHVwdXMgUmVzZWFyY2ggTGFib3JhdG9yeSwgRGl2
aXNpb24gb2YgV29tZW4mYXBvcztzIEhlYWx0aCwgS2luZyZhcG9zO3MgQ29sbGVnZSBMb25kb24s
IFRoZSBSYXluZSBJbnN0aXR1dGUsIFN0IFRob21hcyZhcG9zOyBIb3NwaXRhbCwgTG9uZG9uLCBV
SyYjeEE7QXV0b2ltbXVuZSBEaXNlYXNlcyBSZXNlYXJjaCBVbml0LCBEZXBhcnRtZW50IG9mIElu
dGVybmFsIE1lZGljaW5lLCBCaW9jcnVjZXMgSGVhbHRoIFJlc2VhcmNoIEluc3RpdHV0ZSwgVW5p
dmVyc2l0eSBIb3NwaXRhbCBDcnVjZXMsIFVuaXZlcnNpdHkgb2YgdGhlIEJhc3F1ZSBDb3VudHJ5
LCBCaXprYWlhLCBTcGFpbiYjeEE7RXBpZGVtaW9sb2d5IFVuaXQsIGFuZCBEZXBhcnRtZW50IGZv
ciBSaGV1bWF0b2xvZ3ksIEdlcm1hbiBSaGV1bWF0aXNtIFJlc2VhcmNoIENlbnRyZSwgQ2hhcml0
ZSBVbml2ZXJzaXR5IE1lZGljaW5lLCBCZXJsaW4sIEdlcm1hbnkmI3hBO0luc3RpdHV0ZSBvZiBS
aGV1bWF0b2xvZ3ksIFByYWhhLCBDemVjaCBSZXB1YmxpYyYjeEE7UmVzZWFyY2ggTGFib3JhdG9y
aWVzIGFuZCBBY2FkZW1pYyBEaXZpc2lvbiBvZiBDbGluaWNhbCBSaGV1bWF0b2xvZ3ksIERlcGFy
dG1lbnQgb2YgSW50ZXJuYWwgTWVkaWNpbmUsIFVuaXZlcnNpdHkgb2YgR2Vub3ZhLCBHZW5vdmEs
IEl0YWx5JiN4QTtFVUxBUiBTb2NpYWwgTGVhZ3VlcyBQYXRpZW50cyZhcG9zOyByZXByZXNlbnRh
dGl2ZSwgTGV1dmVuLCBCZWxnaXVtJiN4QTtFVUxBUiBTb2NpYWwgTGVhZ3VlcyBQYXRpZW50cyZh
cG9zOyByZXByZXNlbnRhdGl2ZSwgWnVyaWNoLCBTd2l0emVybGFuZCYjeEE7TmF0aW9uYWwgU2Vy
dmljZSBmb3IgUHJlZ25hbmN5IGFuZCBSaGV1bWF0aWMgRGlzZWFzZXMsIERlcGFydG1lbnQgb2Yg
UmhldW1hdG9sb2d5LCBUcm9uZGhlaW0gVW5pdmVyc2l0eSBIb3NwaXRhbCwgVHJvbmRoZWltLCBO
b3J3YXkgRGVwYXJ0bWVudCBvZiBOZXVyb3NjaWVuY2UsIE5vcndlZ2lhbiBVbml2ZXJzaXR5IG9m
IFNjaWVuY2UgYW5kIFRlY2hub2xvZ3kgKE5UTlUpLCBUcm9uZGhlaW0sIE5vcndheTwvQWRkcmVz
cz48V2ViX1VSTD5QTToyNjg4ODk0ODwvV2ViX1VSTD48WlpfSm91cm5hbEZ1bGw+PGYgbmFtZT0i
U3lzdGVtIj5Bbm4gUmhldW0gRGlzPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+
MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PC9SZWZtYW4+
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkfDtnRlc3RhbSBTa29ycGVuIEMuPC9BdXRob3I+PFllYXI+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ADDIN EN.CITE.DATA 121 In some countries, parenteral gold is still utilized and, while clinical efficacy is undisputed, there are controversies regarding its safety;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhdSBSPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48UmVj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=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhdSBSPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48UmVj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=
ADDIN EN.CITE.DATA 122;123 in other countries gold salts are not available any more. In contrast, the use of antimalarials, such as hydroxychloroquine and chloroquine, is still substantial, especially in combination therapyPFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1vcmVsYW5kPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1vcmVsYW5kPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48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ADDIN EN.CITE.DATA 108 or as monotherapy in patients with very mild disease, ADDIN REFMGR.CITE <Refman><Cite><Author>Katz</Author><Year>2011</Year><RecNum>2577</RecNum><IDText>Re-evaluation of antimalarials in treating rheumatic diseases: re-appreciation and insights into new mechanisms of action</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2577</Ref_ID><Title_Primary>Re-evaluation of antimalarials in treating rheumatic diseases: re-appreciation and insights into new mechanisms of action</Title_Primary><Authors_Primary>Katz,S.J.</Authors_Primary><Authors_Primary>Russell,A.S.</Authors_Primary><Date_Primary>2011/5</Date_Primary><Keywords>Annexin A5</Keywords><Keywords>antagonists & inhibitors</Keywords><Keywords>Antimalarials</Keywords><Keywords>Antiphospholipid Syndrome</Keywords><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>blood</Keywords><Keywords>Canada</Keywords><Keywords>Cardiovascular Diseases</Keywords><Keywords>Chloroquine</Keywords><Keywords>Disease</Keywords><Keywords>drug therapy</Keywords><Keywords>Glucose</Keywords><Keywords>Humans</Keywords><Keywords>Hydroxychloroquine</Keywords><Keywords>Hyperlipidemia</Keywords><Keywords>immunology</Keywords><Keywords>metabolism</Keywords><Keywords>physiopathology</Keywords><Keywords>prevention & control</Keywords><Keywords>Rheumatic Diseases</Keywords><Keywords>Syndrome</Keywords><Keywords>therapeutic use</Keywords><Keywords>Toll-Like Receptors</Keywords><Reprint>Not in File</Reprint><Start_Page>278</Start_Page><End_Page>281</End_Page><Periodical>Curr.Opin.Rheumatol.</Periodical><Volume>23</Volume><Issue>3</Issue><Misc_3>10.1097/BOR.0b013e32834456bf [doi];00002281-201105000-00011 [pii]</Misc_3><Address>Department of Medicine, University of Alberta, Edmonton, Alberta, Canada</Address><Web_URL>PM:21448012</Web_URL><ZZ_JournalStdAbbrev><f name="System">Curr.Opin.Rheumatol.</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>124 especially in China. Interestingly, antimalarials may have significant positive effects on lipid and glucose metabolism ADDIN REFMGR.CITE <Refman><Cite><Author>Hage</Author><Year>2014</Year><RecNum>3060</RecNum><IDText>A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3060</Ref_ID><Title_Primary>A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role</Title_Primary><Authors_Primary>Hage,M.P.</Authors_Primary><Authors_Primary>Al-Badri,M.R.</Authors_Primary><Authors_Primary>Azar,S.T.</Authors_Primary><Date_Primary>2014/8</Date_Primary><Keywords>Diabetes Mellitus</Keywords><Keywords>Disease</Keywords><Keywords>Glucose</Keywords><Keywords>Hydroxychloroquine</Keywords><Keywords>Insulin</Keywords><Keywords>Lipid Metabolism</Keywords><Keywords>metabolism</Keywords><Keywords>Rheumatic Diseases</Keywords><Keywords>Risk</Keywords><Keywords>Syndrome</Keywords><Reprint>Not in File</Reprint><Start_Page>77</Start_Page><End_Page>85</End_Page><Periodical>Ther.Adv.Endocrinol.Metab</Periodical><Volume>5</Volume><Issue>4</Issue><User_Def_5>PMC4206615</User_Def_5><Misc_3>10.1177/2042018814547204 [doi];10.1177_2042018814547204 [pii]</Misc_3><Address>Department of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut-Medical Center, New York, USA
Department of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut-Medical Center, New York, USA
Department of Internal Medicine, Division of Endocrinology and Metabolism, American University of Beirut-Medical Center, 3 Dag Hammarskjold Plaza, 8th floor, New York, NY 10017, USA</Address><Web_URL>PM:25343023</Web_URL><ZZ_JournalStdAbbrev><f name="System">Ther.Adv.Endocrinol.Metab</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>125 and may reduce cardiovascular risk in RA.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNoYXJtYTwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNoYXJtYTwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN EN.CITE.DATA 126 However, joint damage is not retarded to a similar extent as with other csDMARDs. ADDIN REFMGR.CITE <Refman><Cite><Author>Van der Heijde</Author><Year>1990</Year><RecNum>206</RecNum><IDText>Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3- year follow-up</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>206</Ref_ID><Title_Primary>Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3- year follow-up</Title_Primary><Authors_Primary>Van der Heijde,D.M.</Authors_Primary><Authors_Primary>van Riel,P.L.</Authors_Primary><Authors_Primary>Nuver-Zwart,I.H.</Authors_Primary><Authors_Primary>van de Putte,L.B.</Authors_Primary><Date_Primary>1990/3/3</Date_Primary><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Comparative Study</Keywords><Keywords>Double-Blind Method</Keywords><Keywords>Drug Evaluation</Keywords><Keywords>drug therapy</Keywords><Keywords>Follow-Up Studies</Keywords><Keywords>Human</Keywords><Keywords>Hydroxychloroquine</Keywords><Keywords>Randomized Controlled Trials</Keywords><Keywords>Sulfasalazine</Keywords><Keywords>therapeutic use</Keywords><Reprint>Not in File</Reprint><Start_Page>539</Start_Page><Periodical>Lancet</Periodical><Volume>335</Volume><Issue>8688</Issue><Web_URL>PM:1968547</Web_URL><ZZ_JournalFull><f name="System">Lancet</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>127 This recommendation also uses the term “treatment strategy” implying, as with MTX, that leflunomide and sulfasalazine can be used as monotherapy or in combination with other csDMARDs or biologic agents.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmFuZ2ZlbGQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmFuZ2ZlbGQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy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ADDIN EN.CITE.DATA 128-131 Indeed, step-up combination therapy is frequently employed, even though trials comparing step-up combination to csDMARD switching did not reveal significant differences in outcomes. ADDIN REFMGR.CITE <Refman><Cite><Author>Goekoop-Ruiterman YP</Author><Year>2005</Year><RecNum>849</RecNum><IDText>Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial.</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>849</Ref_ID><Title_Primary>Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial.</Title_Primary><Authors_Primary>Goekoop-Ruiterman YP</Authors_Primary><Authors_Primary>De Vries-Bouwstra JK</Authors_Primary><Authors_Primary>Allaart CF</Authors_Primary><Authors_Primary>Van Zeben D</Authors_Primary><Authors_Primary>Kerstens PJ</Authors_Primary><Authors_Primary>Hazes JM</Authors_Primary><Authors_Primary>Zwinderman AH</Authors_Primary><Authors_Primary>Ronday HK</Authors_Primary><Authors_Primary>Han KH</Authors_Primary><Authors_Primary>Westedt ML</Authors_Primary><Authors_Primary>Gerards AH</Authors_Primary><Authors_Primary>van Groenendael JH</Authors_Primary><Authors_Primary>Lems WF</Authors_Primary><Authors_Primary>Van Krugten MV</Authors_Primary><Authors_Primary>Breedveld,F.C.</Authors_Primary><Authors_Primary>Dijkmans BA</Authors_Primary><Date_Primary>2005</Date_Primary><Keywords>Arthritis</Keywords><Keywords>methods</Keywords><Keywords>therapy</Keywords><Keywords>Tumor Necrosis Factor</Keywords><Keywords>Joints</Keywords><Reprint>In File</Reprint><Start_Page>3381</Start_Page><End_Page>3390</End_Page><Periodical>Arthritis Rheum</Periodical><Volume>52</Volume><ZZ_JournalFull><f name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>132 LoE 1a; LoA 9.0Short-term glucocorticoids should be considered when initiating or changing csDMARDs, in different dose regimens and routes of administration, but should be tapered as rapidly as clinically feasible. The added efficacy of glucocorticoids when combined with csDMARDs is well established. Indeed, hitherto all trials comparing gulcocorticoids plus csDMARD with biologics combined with csDMARD revealed similar efficacy..PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdvZWtvb3AtUnVpdGVybWFuIFlQPC9BdXRob3I+PFllYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdvZWtvb3AtUnVpdGVybWFuIFlQPC9BdXRob3I+PFllYXI+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ADDIN EN.CITE.DATA 132;133 In 2013, glucocorticoids were dealt with in recommendation 7, but the wording was different: “Low-dose glucocorticoids should be considered as part of the initial treatment strategy (in combination with one or more csDMARDs) for up to 6 months, but should be tapered as rapidly as clinically feasible”. The current wording constitutes a compromise attempting to accommodate most of the concerns and suggestions raised during the Task Force’s debate. The term “low-dose” was critically discussed. While all members of the Task Force agreed that high doses of glucocorticoids should not be used for prolonged periods, it also became clear that the label “low-dose” (which means a daily dose of 7.5mg or less prednisone per day)PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkR1cnU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO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=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkR1cnU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO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=
ADDIN EN.CITE.DATA 134;135 does not capture several current ways of glucocorticoid application. Indeed, recent clinical trials have revealed the efficacy of short-term glucocorticoids, but at doses >7.5mg per day, namely orally at 30mg starting dose,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA 112 as a single intramuscular injection of 120mg methylprednisolonePFJlZm1hbj48Q2l0ZT48QXV0aG9yPmRlIEpvbmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPmRlIEpvbmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS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ADDIN EN.CITE.DATA 111 or as a single 250mg intravenous pulse therapy of methylprednisolone.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk5hbTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk5hbTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051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ADDIN EN.CITE.DATA 133 Therefore, the term “low-dose” was deleted and replaced by “short-term”, leaving the choice about “dose regimens and routes of administration” (another new piece of wording in this item) to the individual rheumatologist and patient. Indeed, it was argued that a single intramuscular or intravenous application entails a much lower cumulative dose than a few weeks of oral low-dose therapy, but this view was not shared by all Task Force members. Yet another change involved the replacement of the phrase “part of the initial treatment strategy” by “when initiating or changing csDMARDs”. This change clarifies the intention of the Task Force, in that glucocorticoids should be considered with all csDMARD starts, either as part of a first csDMARD therapy at the time of diagnosis or subsequently if an initial strategy has failed. To reflect this change, the algorithm depicted in Figure 1 was modified to show a “+” for the use of glucocorticoids in the new version rather than a “±” as previously. Finally, the fact that csDMARDs are mentioned specifically implies that glucocorticoids are typically not needed as a bridging therapy when bDMARDs or tsDMARDs are used, as these usually have a rapid onset of action and the infection risks may be potentiatedPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxpc3Rpbmc8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxpc3Rpbmc8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS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ADDIN EN.CITE.DATA 136;137 Thus, it is important to reiterate that the Task Force recommends using glucocorticoids in combination with csDMARDs primarily as bridging therapy until the csDMARD reaches its maximum effect, and this should be done using one of the dosing and tapering approaches mentioned above, for which respective evidence exists. By stating “…tapered as rapidly as clinically feasible” the Task Force underlines that glucocorticoids should be gradually reduced and ultimately stopped, usually within 3 months from treatment start and only exceptionally by 6 months. Long-term use of glucocorticoids, especially at doses above 5mg per day, should be avoided because of the many potential risks presented in the SLR.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmVobDwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl
Y051bT4zMTI1PC9SZWNOdW0+PElEVGV4dD5EZWZpbmluZyBjb25kaXRpb25zIHdoZXJlIGxvbmct
dGVybSBnbHVjb2NvcnRpY29pZCB0cmVhdG1lbnQgaGFzIGFuIGFjY2VwdGFibHkgbG93IGxldmVs
IG9mIGhhcm0gdG8gZmFjaWxpdGF0ZSBpbXBsZW1lbnRhdGlvbiBvZiBleGlzdGluZyByZWNvbW1l
bmRhdGlvbnM6IHZpZXdwb2ludHMgZnJvbSBhbiBFVUxBUiB0YXNrIGZvcmNlPC9JRFRleHQ+PE1E
TCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+
MzEyNTwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PkRlZmluaW5nIGNvbmRpdGlvbnMgd2hlcmUgbG9u
Zy10ZXJtIGdsdWNvY29ydGljb2lkIHRyZWF0bWVudCBoYXMgYW4gYWNjZXB0YWJseSBsb3cgbGV2
ZWwgb2YgaGFybSB0byBmYWNpbGl0YXRlIGltcGxlbWVudGF0aW9uIG9mIGV4aXN0aW5nIHJlY29t
bWVuZGF0aW9uczogdmlld3BvaW50cyBmcm9tIGFuIEVVTEFSIHRhc2sgZm9yY2U8L1RpdGxlX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TdHJlaGwsQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkJpamxzbWEsSi5XLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
RGUsV2l0IE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Cb2VycyxNLjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q2FleWVycyxOLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+Q3V0b2xvLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5EYXNndXB0YSxCLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RGl4b24s
Vy5HLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+R2VlbmVuLFIuPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5IdWl6aW5nYSxULlcuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5LZW50LEEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5kZSBUaHVyYWgsQS5MLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGlzdGlu
ZyxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TWFyaWV0dGUsWC48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlJheSxELlcuPC9BdXRob3JzX1ByaW1hcnk+PEF1
dGhvcnNfUHJpbWFyeT5TY2hlcmVyLEguVS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PlNlcm9yLFIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TcGllcyxDLk0u
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5UYXJwLFMuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5XaWVrLEQuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5XaW50aHJvcCxLLkwuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5CdXR0
Z2VyZWl0LEYuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4yMDE2LzY8L0RhdGVfUHJp
bWFyeT48S2V5d29yZHM+YWR2ZXJzZSBlZmZlY3RzPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJp
dGlzPC9LZXl3b3Jkcz48S2V5d29yZHM+Q2FyZGlvdmFzY3VsYXIgRGlzZWFzZXM8L0tleXdvcmRz
PjxLZXl3b3Jkcz5Db25zZW5zdXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5EZW5tYXJrPC9LZXl3b3Jk
cz48S2V5d29yZHM+RGlzZWFzZTwvS2V5d29yZHM+PEtleXdvcmRzPmVwaWRlbWlvbG9neTwvS2V5
d29yZHM+PEtleXdvcmRzPkZyYW5jZTwvS2V5d29yZHM+PEtleXdvcmRzPkdlcm1hbnk8L0tleXdv
cmRzPjxLZXl3b3Jkcz5HbHVjb2NvcnRpY29pZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5IZWFsdGg8
L0tleXdvcmRzPjxLZXl3b3Jkcz5pbW11bm9sb2d5PC9LZXl3b3Jkcz48S2V5d29yZHM+SW5mZWN0
aW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+SW5mbGFtbWF0aW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+
SXRhbHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5OZXRoZXJsYW5kczwvS2V5d29yZHM+PEtleXdvcmRz
Pk9zdGVvcG9yb3NpczwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5
d29yZHM+UHJlZG5pc29uZTwvS2V5d29yZHM+PEtleXdvcmRzPnBzeWNob2xvZ3k8L0tleXdvcmRz
PjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRpYyBEaXNlYXNl
czwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5d29yZHM+PEtleXdvcmRzPlJp
c2s8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrIEZhY3RvcnM8L0tleXdvcmRzPjxLZXl3b3Jkcz50
aGVyYXB5PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFn
ZT45NTI8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjk1NzwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QW5u
IFJoZXVtIERpczwvUGVyaW9kaWNhbD48Vm9sdW1lPjc1PC9Wb2x1bWU+PElzc3VlPjY8L0lzc3Vl
PjxNaXNjXzM+YW5ucmhldW1kaXMtMjAxNS0yMDg5MTYgW3BpaV07MTAuMTEzNi9hbm5yaGV1bWRp
cy0yMDE1LTIwODkxNiBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPkRlcGFydG1lbnQgb2YgUmhldW1h
dG9sb2d5IGFuZCBDbGluaWNhbCBJbW11bm9sb2d5LCBDaGFyaXRlIFVuaXZlcnNpdHkgTWVkaWNp
bmUsIEJlcmxpbiwgR2VybWFueSYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3kgYW5kIENs
aW5pY2FsIEltbXVub2xvZ3ksIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50cmUgVXRyZWNodCwgVXRy
ZWNodCwgdGhlIE5ldGhlcmxhbmRzIEFtc3RlcmRhbSBSaGV1bWF0b2xvZ3kmYW1wOyBJbW11bm9s
b2d5IENlbnRlciwgVlUgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgQW1zdGVyZGFtLCB0aGUg
TmV0aGVybGFuZHMmI3hBO01lZGljYWwgSHVtYW5pdGllcywgVlUgTWVkaWNhbCBDZW50cmUsIEFt
c3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzJiN4QTtBbXN0ZXJkYW0gUmhldW1hdG9sb2d5JmFtcDsg
SW1tdW5vbG9neSBDZW50ZXIsIFZVIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIEFtc3RlcmRh
bSwgdGhlIE5ldGhlcmxhbmRzIERlcGFydG1lbnQgb2YgRXBpZGVtaW9sb2d5ICZhbXA7IEJpb3N0
YXRpc3RpY3MsIFZVIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIEFtc3RlcmRhbSwgdGhlIE5l
dGhlcmxhbmRzJiN4QTtQYXRpZW50IFJlc2VhcmNoIFBhcnRuZXIsIE1vbCwgQmVsZ2l1bSYjeEE7
RGVwYXJ0bWVudCBvZiBJbnRlcm5hbCBNZWRpY2luZSwgUmVzZWFyY2ggTGFib3JhdG9yeSAmYW1w
OyBBY2FkZW1pYyBEaXZpc2lvbiBvZiBDbGluaWNhbCBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkg
b2YgR2Vub2EsIEdlbm92YSwgSXRhbHkmI3hBO1NvdXRoZW5kIFVuaXZlcnNpdHkgSG9zcGl0YWwg
TkhTIEZvdW5kYXRpb24gVHJ1c3QsIFdlc3RjbGlmZi1vbi1TZWEsIEVzc2V4LCBVSyYjeEE7QXJ0
aHJpdGlzIFJlc2VhcmNoIFVLIENlbnRyZSBmb3IgRXBpZGVtaW9sb2d5LCBDZW50cmUgZm9yIE11
c2N1bG9za2VsZXRhbCBSZXNlYXJjaCwgSW5zdGl0dXRlIG9mIEluZmxhbW1hdGlvbiBhbmQgUmVw
YWlyLCBVbml2ZXJzaXR5IG9mIE1hbmNoZXN0ZXIsIE1hbmNoZXN0ZXIsIFVLJiN4QTtEZXBhcnRt
ZW50IG9mIENsaW5pY2FsICZhbXA7IEhlYWx0aCBQc3ljaG9sb2d5LCBVdHJlY2h0IFVuaXZlcnNp
dHksIFV0cmVjaHQsIHRoZSBOZXRoZXJsYW5kcyYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xv
Z3ksIExlaWRlbiBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBMZWlkZW4sIHRoZSBOZXRoZXJs
YW5kcyYjeEE7U2FsaXNidXJ5IEZvdW5kYXRpb24gVHJ1c3QgTkhTIEhvc3BpdGFsLCBXaWx0c2hp
cmUsIFVLJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgQWFyaHVzIFVuaXZlcnNpdHkg
SG9zcGl0YWwsIEFhcmh1cywgRGVubWFyayYjeEE7RXBpZGVtaW9sb2d5IFVuaXQsIEdlcm1hbiBS
aGV1bWF0aXNtIFJlc2VhcmNoIENlbnRyZSwgQmVybGluLCBHZXJtYW55JiN4QTtEZXBhcnRtZW50
IG9mIFJoZXVtYXRvbG9neSwgQXNzaXN0YW5jZSBQdWJsaXF1ZS1Ib3BpdGF1eCBkZSBQYXJpcywg
SG9waXRhdXggVW5pdmVyc2l0YWlyZXMgUGFyaXMtU3VkLCBMZSBLcmVtbGluIEJpY2V0cmUsIEZy
YW5jZSBVbml2ZXJzaXRlIFBhcmlzLVN1ZDsgSU5TRVJNIFUxMTg0LCBMZSBLcmVtbGluIEJpY2V0
cmUsIEZyYW5jZSYjeEE7RmFjdWx0eSBvZiBNZWRpY2FsIGFuZCBIZWFsdGggU2NpZW5jZXMsIFVu
aXZlcnNpdHkgb2YgTWFuY2hlc3RlciwgTWFuY2hlc3RlciwgVUsmI3hBO0RlcGFydG1lbnQgb2Yg
UmhldW1hdG9sb2d5LCBMZWlkZW4gVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRlciwgTGVpZGVuLCB0
aGUgTmV0aGVybGFuZHMmI3hBO0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5LCBBc3Npc3RhbmNl
IFB1YmxpcXVlLUhvcGl0YXV4IGRlIFBhcmlzLCBIb3BpdGF1eCBVbml2ZXJzaXRhaXJlcyBQYXJp
cy1TdWQsIExlIEtyZW1saW4gQmljZXRyZSwgRnJhbmNlIFVuaXZlcnNpdGUgUGFyaXMtU3VkOyBJ
TlNFUk0gVTExODQsIExlIEtyZW1saW4gQmljZXRyZSwgRnJhbmNlJiN4QTtEZXBhcnRtZW50IG9m
IFJoZXVtYXRvbG9neSBhbmQgQ2xpbmljYWwgSW1tdW5vbG9neSwgQ2hhcml0ZSBVbml2ZXJzaXR5
IE1lZGljaW5lLCBCZXJsaW4sIEdlcm1hbnkmI3hBO0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5
LCBUaGUgUGFya2VyIEluc3RpdHV0ZSwgQ29wZW5oYWdlbiBVbml2ZXJzaXR5IEhvc3BpdGFsLCBC
aXNwZWJqZXJnIGFuZCBGcmVkZXJpa3NiZXJnLCBEZW5tYXJrJiN4QTtEZXV0c2NoZSBSZXVtYS1M
aWdhLCBCb25uLCBHZXJtYW55JiN4QTtEaXZpc2lvbnMgb2YgSW5mZWN0aW91cyBEaXNlYXNlcywg
T3JlZ29uIEhlYWx0aCAmYW1wOyBTY2llbmNlIFVuaXZlcnNpdHksIFBvcnRsYW5kLCBVU0EmI3hB
O0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5IGFuZCBDbGluaWNhbCBJbW11bm9sb2d5LCBDaGFy
aXRlIFVuaXZlcnNpdHkgTWVkaWNpbmUsIEJlcmxpbiwgR2VybWFueTwvQWRkcmVzcz48V2ViX1VS
TD5QTToyNjkzMzE0NjwvV2ViX1VSTD48WlpfSm91cm5hbEZ1bGw+PGYgbmFtZT0iU3lzdGVtIj5B
bm4gUmhldW0gRGlzPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29y
a2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5DaGF0emlkaW9ueXNpb3UgSzwvQXV0
aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJlY051bT4zMTM4PC9SZWNOdW0+PElEVGV4dD5TTFIgb24g
Y3NETUFSRHMgdG8gaW5mb3JtIHRoZSBFVUxBUiBSQSBtYW5hZ2VtZW50IHRhc2sgZm9yY2UgMjAx
NjwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZf
VHlwZT48UmVmX0lEPjMxMzg8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5TTFIgb24gY3NETUFSRHMg
dG8gaW5mb3JtIHRoZSBFVUxBUiBSQSBtYW5hZ2VtZW50IHRhc2sgZm9yY2UgMjAxNjwvVGl0bGVf
UHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkNoYXR6aWRpb255c2lvdSBLPC9BdXRob3JzX1ByaW1h
cnk+PERhdGVfUHJpbWFyeT4yMDE2PC9EYXRlX1ByaW1hcnk+PFJlcHJpbnQ+Tm90IGluIEZpbGU8
L1JlcHJpbnQ+PFBlcmlvZGljYWw+QW5uIFJoZXVtIERpcyAoc3VibWl0dGVkKTwvUGVyaW9kaWNh
bD48WlpfSm91cm5hbEZ1bGw+PGYgbmFtZT0iU3lzdGVtIj5Bbm4gUmhldW0gRGlzIChzdWJtaXR0
ZWQpPC9mPjwvWlpfSm91cm5hbEZ1bGw+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48
L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5SYW1pcm8gUzwvQXV0aG9yPjxZZWFyPjIwMTY8L1ll
YXI+PFJlY051bT4zMTM5PC9SZWNOdW0+PElEVGV4dD5TTFIgb24gc2FmZXR5IGFzcGVjdHMgb2Yg
RE1BUkRzIHRvIGluZm9ybSB0aGUgRVVMQVIgUkEgbWFuYWdlbWVudCB0YXNrIGZvcmNlPC9JRFRl
eHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxS
ZWZfSUQ+MzEzOTwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PlNMUiBvbiBzYWZldHkgYXNwZWN0cyBv
ZiBETUFSRHMgdG8gaW5mb3JtIHRoZSBFVUxBUiBSQSBtYW5hZ2VtZW50IHRhc2sgZm9yY2U8L1Rp
dGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5SYW1pcm8gUzwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+ZXQgYWw8L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTY8
L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+U2FmZXR5PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4g
RmlsZTwvUmVwcmludD48UGVyaW9kaWNhbD5Bbm4gUmhldW0gRGlzIChzdWJtaXR0ZWQpPC9QZXJp
b2RpY2FsPjxaWl9Kb3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFubiBSaGV1bSBEaXMgKHN1
Ym1pdHRlZCk8L2Y+PC9aWl9Kb3VybmFsRnVsbD48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9y
bUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1hbj4A
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmVobDwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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ADDIN EN.CITE.DATA 48;50;55 While some of these risk associations may be due to confounding by indication in patients with high disease activity,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBTaWpsPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPnZhbiBTaWpsPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48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ADDIN EN.CITE.DATA 138 the evidence for increased overall and cardiovascular mortality at a dose above a threshold of 7.5mg/day or a cumulative dose of 40g is considerable.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRlbCBSaW5jbzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+
PFJlY051bT4zMDY0PC9SZWNOdW0+PElEVGV4dD5HbHVjb2NvcnRpY29pZCBkb3NlIHRocmVzaG9s
ZHMgYXNzb2NpYXRlZCB3aXRoIGFsbC1jYXVzZSBhbmQgY2FyZGlvdmFzY3VsYXIgbW9ydGFsaXR5
IGluIHJoZXVtYXRvaWQgYXJ0aHJpdGlzPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+
PFJlZl9UeXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MzA2NDwvUmVmX0lEPjxUaXRsZV9Q
cmltYXJ5PkdsdWNvY29ydGljb2lkIGRvc2UgdGhyZXNob2xkcyBhc3NvY2lhdGVkIHdpdGggYWxs
LWNhdXNlIGFuZCBjYXJkaW92YXNjdWxhciBtb3J0YWxpdHkgaW4gcmhldW1hdG9pZCBhcnRocml0
aXM8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EZWwgUmluY28sSTwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QmF0dGFmYXJhbm8sRC5GLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+UmVzdHJlcG8sSi5GLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+RXJpa3NvbixKLk0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5F
c2NhbGFudGUsQS48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTQvMjwvRGF0ZV9Q
cmltYXJ5PjxLZXl3b3Jkcz5BZHVsdDwvS2V5d29yZHM+PEtleXdvcmRzPmFkdmVyc2UgZWZmZWN0
czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhy
aXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+Q2FyZGlvdmFzY3VsYXIgRGlzZWFz
ZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Eb3NlLVJlc3BvbnNlIFJlbGF0aW9uc2hpcCxEcnVnPC9L
ZXl3b3Jkcz48S2V5d29yZHM+ZHJ1ZyB0aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+RmVtYWxl
PC9LZXl3b3Jkcz48S2V5d29yZHM+R2x1Y29jb3J0aWNvaWRzPC9LZXl3b3Jkcz48S2V5d29yZHM+
SGVhbHRoPC9LZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+SW5j
aWRlbmNlPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5d29yZHM+PEtleXdvcmRzPk1heGlt
dW0gVG9sZXJhdGVkIERvc2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48
S2V5d29yZHM+TWlkZGxlIEFnZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5Nb3J0YWxpdHk8L0tleXdv
cmRzPjxLZXl3b3Jkcz5NdWx0aWNlbnRlciBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5d29yZHM+UGF0
aWVudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5QcmVkbmlzb25lPC9LZXl3b3Jkcz48S2V5d29yZHM+
UHJvcG9ydGlvbmFsIEhhemFyZHMgTW9kZWxzPC9LZXl3b3Jkcz48S2V5d29yZHM+UmVzZWFyY2g8
L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXRyb3NwZWN0aXZlIFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5SaGV1bWF0b2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrPC9LZXl3b3Jkcz48S2V5
d29yZHM+UmlzayBGYWN0b3JzPC9LZXl3b3Jkcz48S2V5d29yZHM+U3Vydml2YWwgUmF0ZTwvS2V5
d29yZHM+PEtleXdvcmRzPlRleGFzPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFwZXV0aWMgdXNl
PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4yNjQ8
L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjI3MjwvRW5kX1BhZ2U+PFBlcmlvZGljYWw+QXJ0aHJpdGlz
IFJoZXVtYXRvbDwvUGVyaW9kaWNhbD48Vm9sdW1lPjY2PC9Wb2x1bWU+PElzc3VlPjI8L0lzc3Vl
PjxNaXNjXzM+MTAuMTAwMi9hcnQuMzgyMTAgW2RvaV08L01pc2NfMz48QWRkcmVzcz5Vbml2ZXJz
aXR5IG9mIFRleGFzIEhlYWx0aCBTY2llbmNlIENlbnRlciBhdCwgU2FuIEFudG9uaW88L0FkZHJl
c3M+PFdlYl9VUkw+PHU+UE06MjQ1MDQ3OTg8L3U+PC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJi
cmV2PjxmIG5hbWU9IlN5c3RlbSI+QXJ0aHJpdGlzIFJoZXVtYXRvbDwvZj48L1paX0pvdXJuYWxT
dGRBYmJyZXY+PFpaX1dvcmtmb3JtSUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PC9S
ZWZtYW4+AG==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRlbCBSaW5jbzwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+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ADDIN EN.CITE.DATA 139 Of note, applying glucocorticoids as a sole therapeutic change in patients with insufficient response to csDMARD therapy does not convey good efficacy and is associated with significant adverse events.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNob3k8L0F1dGhvcj48WWVhcj4yMDA1PC9ZZWFyPjxSZWNO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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkNob3k8L0F1dGhvcj48WWVhcj4yMDA1PC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA 140 Moreover, if glucocorticoids cannot be withdrawn with the time frame mentioned above, the DMARD therapy may have to be considered a failure. Finally, intra-articular glucocorticoid application may have to be considered in certain instances, such as a residually inflamed or a reactivated joint.Some Task Force members advocated the chronic use of glucocorticoids as a possibility for some patients, however, this proposal was not endorsed by the majority. While the bullet point on glucocorticoids was, as in previous years, most heavily debated, the final wording received a 98% majority vote. The level of agreement, though, was much lower (8.7), in line with previous versions of the recommendations. This relatively low level of agreement is presumably due to the fact that many task force members felt that this point was too liberal and the use of glucocorticoids should be more restricted, while others were of the opinion that it was too restrictive, exaggerating adverse event reporting confounded by indication. LoE 1a; LoA 8.7If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors, other csDMARDs should be considered. This sentence constitutes the first part of previous recommendation 8. It is essentially worded in an identical way, except that the last portion, “change to another csDMARD strategy should be considered”, was reworded as “other csDMARDs should be considered”, in light of the fact that combination with glucocorticoids has now been recommended clearly also for this step of the treatment algorithm (item 6) and that combinations of csDMARDs are not specifically recommended as initial treatment strategy anymore. The poor prognostic factors are presented in Table 1. The Task Force also discussed that early intolerance for a csDMARD should not be considered as a treatment failure, which would imply moving immediately to the next phase of the algorithm, but rather require re-institution of another (replacement) first csDMARD. This recommendation was approved by 94% of the 48 voters. LoE 5; LoA 8.5If the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, addition of a bDMARD* or a tsDMARD should be considered; current practice would be to start a bDMARD§. The separation of the 2nd part of previous recommendation 8 (“when poor prognostic factors are present, addition of a bDMARD should be considered”) and the new item 7 reflects the Task Force’s desire to give stratification by prognostic factors more prominence. The bDMARDs currently available include a series of TNF-inhibitors (adalimumab, certolizumab, etanercept, golimumab and infliximab); abatacept (a costimulation inhibitor); tocilizumab (an IL-6 receptor blocker, but in the future also possibly another IL-6 receptor inhibitor, sarilumab, and an IL-6 inhibitor, sirukumab); rituximab (an anti-B-cell agent); both as boDMARDs and as EMA- or FDA- approved bsDMARDs. This recommendation was also expanded to include tsDMARDs, namely the Jak inhibitor tofacitinib and possibly further Jak inhibitors, such as baricitinib. In the 2013 update, tsDMARDs (bullet point 11) were recommended for use after a bDMARD had failed. Since then, more data on tofacitinib, especially regarding long-term safety aspects, and new data for baricitinib have been published. The data suggest that baricitinib may be more efficacious than a TNF-inhibitor. ADDIN REFMGR.CITE <Refman><Cite><Author>Taylor PC</Author><Year>2015</Year><RecNum>2921</RecNum><IDText>Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study. [Abstract]</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2921</Ref_ID><Title_Primary>Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study. [Abstract]</Title_Primary><Authors_Primary>Taylor PC</Authors_Primary><Authors_Primary>Keystone EC</Authors_Primary><Authors_Primary>van der Heijde D</Authors_Primary><Authors_Primary>Tanaka Y</Authors_Primary><Authors_Primary>Ishii T</Authors_Primary><Authors_Primary>Emoto K</Authors_Primary><Authors_Primary>Yang L</Authors_Primary><Authors_Primary>Arora V</Authors_Primary><Authors_Primary>Gaich CL</Authors_Primary><Authors_Primary>Rooney T</Authors_Primary><Authors_Primary>Schlichting D</Authors_Primary><Authors_Primary>Macias W</Authors_Primary><Authors_Primary>de Bono S</Authors_Primary><Authors_Primary>Weinblatt M</Authors_Primary><Date_Primary>2015</Date_Primary><Keywords>Patients</Keywords><Keywords>Arthritis</Keywords><Keywords>Methotrexate</Keywords><Keywords>therapy</Keywords><Reprint>Not in File</Reprint><Start_Page>L2. <f name="Times New Roman">. Accessed January 4, 2016</f></Start_Page><Periodical>Arthritis Rheum</Periodical><Volume>67 (Suppl 10)</Volume><ZZ_JournalFull><f name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>141 Currently, the term tsDMARDs refers only to Janus kinase (Jak) inhibition; tofacitinib is approved in many countries, such as in the USA, Latin America and Asia as well as some European countries, but still not in the European Union. Baricitinib has completed phase 3 trials and is currently under regulatory review; and filgotinib and other Jak inhibitors are undergoing evaluation in clinical trials. However, similar to the 2010 recommendations, in which TNF-inhibitors had been given a slight preference over other biologics due to availability of long-term registry data for the former but not the latter, preference is given here to bDMARDs over Jak inhibitors for the same reason. This notion on current practice is an expert opinion and not based on solid evidence. This bullet point still received a very high vote at the meeting and a high level of agreement. The recommendation to use these agents in patients who have bad prognostic factors (rather than those who have not) is also not based on solid evidence in the literature. However, in most trials of bDMARDs and tsDMARDs the existing inclusion criteria, such as high disease activity, presence of autoantibodies and pre-existing joint damage, assured that patients with bad prognostic factors were included. Nevertheless, formal trials comparing the use of any of these agents in patients with and without bad prognostic markers do not exist. On the other hand, several post-hoc analyses revealed the value of using TNF-inhibitors in patients with bad prognostic markers (Table 1) relative to those without.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhc3Rlc2FlZ2VyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhc3Rlc2FlZ2VyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh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ADDIN EN.CITE.DATA 67;142 The footnote to bDMARDs mentions that all approved bDMARDs may be used without hierarchical positioning, and that EMA- or FDA-approved biosimilars (bsDMARDs) have similar efficacy and safety as the respective biological originator (bo) DMARDs, and should be preferred if they are indeed appreciably cheaper than originator or other bDMARDs or tsDMARDs. Since the 2013 update, several bsDMARDs targeting TNF have been approved in Europe and some in the USA.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPllvbzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJlY051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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPllvbzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJlY051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ADDIN EN.CITE.DATA 143-145 Among the bDMARDs there is no difference in outcomes, irrespective of their target. This conclusion rests on head-to-head trials, meta-analyses, the results of the SLRs, PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbWlybyBTPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlJhbWlybyBTPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48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ADDIN EN.CITE.DATA 48-50;146 and indirect comparison (the latter being less reliable and therefore least informative)PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl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 EN.CITE.DATA 13;147;148 Of note, the SLR also included data from clinical trials of sarilumab, a human anti-IL-6 receptor antibody, and sirukumab, a human anti-IL-6 antibody, both of which are not approved at the present time; based on the SLR, the Task Force regarded these two antibodies and tocilizumab as having similar efficacy and safety. While rituximab is approved for use after TNF-inhibitors have failed, there is ample evidence for its efficacy in bDMARD-na?ve patients and early RA.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJ1Y2g8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNO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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJ1Y2g8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA 58;147 It is, therefore, frequently used after insufficient response to csDMARDs, especially when there are specific contraindications to other biologic agents, such as past lymphoma or demyelinating disorders, given its efficacy in these diseases.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkhhdXNlcjwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkhhdXNlcjwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl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ADDIN EN.CITE.DATA 149;150 The separation of points 7 and 8 was also based on the reason that the previous bullet point comprised of two recommendations and that separating them would give the stratification by prognostic factors better visibility. The poor prognostic factors are presented in Table 1 and now also include failure of two csDMARDs; if patients have insufficient efficacy to two csDMARD courses, either consecutively or as combination, a further csDMARD may have only little additional impact.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdvZWtvb3AtUnVpdGVybWFuPC9BdXRob3I+PFllYXI+MjAw
NzwvWWVhcj48UmVjTnVtPjEyNTE8L1JlY051bT48SURUZXh0PkNvbXBhcmlzb24gb2YgdHJlYXRt
ZW50IHN0cmF0ZWdpZXMgaW4gZWFybHkgcmhldW1hdG9pZCBhcnRocml0aXM6IGEgcmFuZG9taXpl
ZCB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFs
PC9SZWZfVHlwZT48UmVmX0lEPjEyNTE8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5Db21wYXJpc29u
IG9mIHRyZWF0bWVudCBzdHJhdGVnaWVzIGluIGVhcmx5IHJoZXVtYXRvaWQgYXJ0aHJpdGlzOiBh
IHJhbmRvbWl6ZWQgdHJpYWw8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Hb2Vrb29w
LVJ1aXRlcm1hbixZLlAuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5kZSBWcmll
cy1Cb3V3c3RyYSxKLksuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5BbGxhYXJ0
LEMuRi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbixaZWJlbiBELjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2Vyc3RlbnMsUC5KLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+SGF6ZXMsSi5NLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3Jz
X1ByaW1hcnk+WndpbmRlcm1hbixBLkguPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5QZWV0ZXJzLEEuSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlIEpvbmdl
LUJvayxKLk0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NYWxsZWUsQy48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PmRlIEJldXMsVy5NLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+ZGUgU29ubmF2aWxsZSxQLkIuPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5Fd2FscyxKLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5CcmVlZHZlbGQsRi5DLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RGlq
a21hbnMsQi5BLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAwNy8zLzIwPC9EYXRl
X1ByaW1hcnk+PEtleXdvcmRzPmFkdmVyc2UgZWZmZWN0czwvS2V5d29yZHM+PEtleXdvcmRzPkFu
dGktSW5mbGFtbWF0b3J5IEFnZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFudGlib2RpZXM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5BbnRpYm9kaWVzLE1vbm9jbG9uYWw8L0tleXdvcmRzPjxLZXl3b3Jk
cz5BbnRpcmhldW1hdGljIEFnZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5
d29yZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+
Q29tcGFyYXRpdmUgU3R1ZHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5EcnVnIEFkbWluaXN0cmF0aW9u
IFNjaGVkdWxlPC9LZXl3b3Jkcz48S2V5d29yZHM+ZHJ1ZyB0aGVyYXB5PC9LZXl3b3Jkcz48S2V5
d29yZHM+RHJ1ZyBUaGVyYXB5LENvbWJpbmF0aW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5z
PC9LZXl3b3Jkcz48S2V5d29yZHM+TXVsdGljZW50ZXIgU3R1ZGllczwvS2V5d29yZHM+PEtleXdv
cmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+UHJlZG5pc29uZTwvS2V5d29yZHM+PEtl
eXdvcmRzPnJhZGlvZ3JhcGh5PC9LZXl3b3Jkcz48S2V5d29yZHM+UmVzZWFyY2g8L0tleXdvcmRz
PjxLZXl3b3Jkcz5SaGV1bWF0b2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5TaW5nbGUtQmxpbmQg
TWV0aG9kPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFwZXV0aWMgdXNlPC9LZXl3b3Jkcz48S2V5
d29yZHM+dGhlcmFweTwvS2V5d29yZHM+PEtleXdvcmRzPnRveGljaXR5PC9LZXl3b3Jkcz48S2V5
d29yZHM+VHJlYXRtZW50IE91dGNvbWU8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9S
ZXByaW50PjxTdGFydF9QYWdlPjQwNjwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+NDE1PC9FbmRfUGFn
ZT48UGVyaW9kaWNhbD5Bbm4gSW50ZXJuLk1lZC48L1BlcmlvZGljYWw+PFZvbHVtZT4xNDY8L1Zv
bHVtZT48SXNzdWU+NjwvSXNzdWU+PEFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ks
IExlaWRlbiBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBMZWlkZW4sIFRoZSBOZXRoZXJsYW5k
cy4geS5wLm0uZ29la29vcEBsdW1jLm5sPC9BZGRyZXNzPjxXZWJfVVJMPlBNOjE3MzcxODg1PC9X
ZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5hbWU9IlN5c3RlbSI+QW5uIEludGVybi5N
ZWQuPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9y
bUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPktpZWx5PC9BdXRob3I+PFllYXI+MjAxMTwv
WWVhcj48UmVjTnVtPjIzMDM8L1JlY051bT48SURUZXh0Pk91dGNvbWUgaW4gcmhldW1hdG9pZCBh
cnRocml0aXMgcGF0aWVudHMgd2l0aCBjb250aW51ZWQgY29udmVudGlvbmFsIHRoZXJhcHkgZm9y
IG1vZGVyYXRlIGRpc2Vhc2UgYWN0aXZpdHktLXRoZSBlYXJseSBSQSBuZXR3b3JrIChFUkFOKTwv
SURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZfVHlw
ZT48UmVmX0lEPjIzMDM8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5PdXRjb21lIGluIHJoZXVtYXRv
aWQgYXJ0aHJpdGlzIHBhdGllbnRzIHdpdGggY29udGludWVkIGNvbnZlbnRpb25hbCB0aGVyYXB5
IGZvciBtb2RlcmF0ZSBkaXNlYXNlIGFjdGl2aXR5LS10aGUgZWFybHkgUkEgbmV0d29yayAoRVJB
Tik8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LaWVseSxQLjwvQXV0aG9yc19Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+V2Fsc2gsRC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Q
cmltYXJ5PldpbGxpYW1zLFIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Zb3Vu
ZyxBLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxMS81PC9EYXRlX1ByaW1hcnk+
PEtleXdvcmRzPmFudGFnb25pc3RzICZhbXA7IGluaGliaXRvcnM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5BbnRpcmhldW1hdGljIEFnZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5
d29yZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+
Q2FzZSBSZXBvcnQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5Db2hvcnQgU3R1ZGllczwvS2V5d29yZHM+
PEtleXdvcmRzPkRpc2FiaWxpdHkgRXZhbHVhdGlvbjwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vh
c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5G
ZW1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1hbnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Mb25n
aXR1ZGluYWwgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPk1hbGU8L0tleXdvcmRzPjxLZXl3
b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWlkZGxlIEFnZWQ8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5NdWx0aWNlbnRlciBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5d29yZHM+UGF0aWVudHM8
L0tleXdvcmRzPjxLZXl3b3Jkcz5Qcm9zcGVjdGl2ZSBTdHVkaWVzPC9LZXl3b3Jkcz48S2V5d29y
ZHM+UmVzZWFyY2g8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaGV1bWF0b2xvZ3k8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5TZXZlcml0eSBvZiBJbGxuZXNzIEluZGV4PC9LZXl3b3Jkcz48S2V5d29yZHM+dGhl
cmFwZXV0aWMgdXNlPC9LZXl3b3Jkcz48S2V5d29yZHM+dGhlcmFweTwvS2V5d29yZHM+PEtleXdv
cmRzPlRyZWF0bWVudCBPdXRjb21lPC9LZXl3b3Jkcz48S2V5d29yZHM+VHVtb3IgTmVjcm9zaXMg
RmFjdG9yLWFscGhhPC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVwcmludD48U3Rh
cnRfUGFnZT45MjY8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjkzMTwvRW5kX1BhZ2U+PFBlcmlvZGlj
YWw+UmhldW1hdG9sb2d5LihPeGZvcmQpPC9QZXJpb2RpY2FsPjxWb2x1bWU+NTA8L1ZvbHVtZT48
SXNzdWU+NTwvSXNzdWU+PE1pc2NfMz5rZXE0MDYgW3BpaV07MTAuMTA5My9yaGV1bWF0b2xvZ3kv
a2VxNDA2IFtkb2ldPC9NaXNjXzM+PEFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ks
IFN0LiBHZW9yZ2UmYXBvcztzIEhlYWx0aGNhcmUgTkhTIFRydXN0LCBMb25kb24sIFVLPC9BZGRy
ZXNzPjxXZWJfVVJMPlBNOjIxMTY5MzQzPC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2Pjxm
IG5hbWU9IlN5c3RlbSI+UmhldW1hdG9sb2d5LihPeGZvcmQpPC9mPjwvWlpfSm91cm5hbFN0ZEFi
YnJldj48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1h
bj5=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdvZWtvb3AtUnVpdGVybWFuPC9BdXRob3I+PFllYXI+MjAw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ADDIN EN.CITE.DATA 113;151 The Task Force also discussed whether the use of a bDMARD as first-line therapy should be reconsidered, as had been the case in the original 2010 recommendations. Such use has been tested in a large number of randomized trials and has consistently been found to be statistically superior to MTX monotherapy. Importantly, however, none of the respective phase 3 trials used de novo glucocorticoids in the MTX monotherapy arm and the few investigator-initiated studies that compared first-line bDMARDs plus MTX with glucocorticoids plus MTX (or with a combination of csDMARDs) did not show a clear clinical or structural advantage of early bDMARD therapy.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdvZWtvb3AtUnVpdGVybWFuPC9BdXRob3I+PFllYXI+MjAw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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdvZWtvb3AtUnVpdGVybWFuPC9BdXRob3I+PFllYXI+MjAw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ADDIN EN.CITE.DATA 113;133 Thus, this proposal did not find a majority vote. Nevertheless, it is still conceivable that an induction regimen followed by the subsequent cessation of the bDMARD and continuation of the csDMARD may become a valuable option in the future; there is some support in the literature for such an approach.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 66;152-155 However, this would need further confirmation by additional trials before it could be put into place, especially also because the number of initial responders in whom tapering could be considered does not comprise a majority of the patients. The recommendation, as worded above, received 94% of the Task Force members’ votes. LoE *1b, §5; LoA 9.0bDMARDs and tsDMARDs should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and tsDMARDs may have some advantages compared to other bDMARDs. This recommendation replaces former #9 (“In patients responding insufficiently to MTX and/or other csDMARD strategies, with or without glucocorticoids, bDMARDs [TNF inhibitors, abatacept or tocilizumab, and, under certain circumstances, rituximab] should be commenced with MTX”). While the individual bDMARDs and tsDMARDs have been already discussed above, item 9 now refers to the fact that all bDMARDs have superior efficacy when combined with MTX than as monotherapy. Compared with the 2013 update, more evidence has now accrued in favor of combination, even for tocilizumab.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJ1cm1lc3RlcjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJ1cm1lc3RlcjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+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ADDIN EN.CITE.DATA 156-158 Also for baricitinib, combination therapy conveys better structural, though not clinical or functional efficacy than monotherapy. ADDIN REFMGR.CITE <Refman><Cite><Author>Fleischmann R</Author><Year>2015</Year><RecNum>2922</RecNum><IDText>Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results [abstract].</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2922</Ref_ID><Title_Primary>Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results [abstract].</Title_Primary><Authors_Primary>Fleischmann R</Authors_Primary><Authors_Primary>Takeuchi T</Authors_Primary><Authors_Primary>Schlichting D</Authors_Primary><Authors_Primary>Macias WL</Authors_Primary><Authors_Primary>Rooney T</Authors_Primary><Authors_Primary>Grubuz S</Authors_Primary><Authors_Primary>Stoykov I</Authors_Primary><Authors_Primary>Beattie SD</Authors_Primary><Authors_Primary>Kuo WL</Authors_Primary><Authors_Primary>Schiff M</Authors_Primary><Date_Primary>2015</Date_Primary><Keywords>Methotrexate</Keywords><Keywords>Patients</Keywords><Keywords>Arthritis</Keywords><Reprint>Not in File</Reprint><Start_Page><f name="Times New Roman">. Accessed January 4, 2016</f></Start_Page><Periodical>Arhritis Rheum</Periodical><Volume>67 (Suppl 10)</Volume><ZZ_JournalFull><f name="System">Arhritis Rheum</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>159 However, regarding signs and symptoms, physical function and joint damage, there are indications for a somewhat better efficacy of tocilizumab monotherapy, and more strongly so for Jak-inhibitors compared with MTX.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxlZSBFQjwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxlZSBFQjwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+PFJl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ADDIN EN.CITE.DATA 159-161 Monotherapy of the other biologic agents has not been found clinically superior to methotrexate monotherapy.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPktsYXJlc2tvZyBMPC9BdXRob3I+PFllYXI+MjAwNDwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPktsYXJlc2tvZyBMPC9BdXRob3I+PFllYXI+MjAwNDwvWWVh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ADDIN EN.CITE.DATA 64;65;162 MTX can be used at 7.5 to 10mg to provide added efficacy to TNF-inhibitorsPFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1haW5pPC9BdXRob3I+PFllYXI+MTk5ODwvWWVhcj48UmVj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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPk1haW5pPC9BdXRob3I+PFllYXI+MTk5ODwvWWVhcj48UmVj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 EN.CITE.DATA 163;164 and intolerance at these low doses leading to discontinuation is very rare. Moreover, biologics can also be effectively combined with other csDMARDs.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmFuZ2ZlbGQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlN0cmFuZ2ZlbGQ8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFy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ADDIN EN.CITE.DATA 128;130 Another aspect, namely the occurrence of anti-drug antibodies (immunogenicity), was discussed, especially regarding secondary non-response. In this context the lack of knowledge about the role of non-adherence and non-persistence was also addressed. The Task Force then discussed routine testing of anti-drug-antibodies and drug levels and felt that there was little place for these in clinical practice, since a good clinical response would not lead to cessation of therapy even in the presence of anti-drug antibodies, or low drug levels, and vice versa. Of note, the use of MTX at the doses mentioned above reduces the incidence of anti-drug antibodies.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJ1cm1lc3RlcjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkJ1cm1lc3RlcjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+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 EN.CITE.DATA 163;164 For all these reasons the Task Force felt strongly (96% majority) that bDMARDs (and tsDMARDs) should primarily be added to, i.e. combined with csDMARDs, such as leflunomide, leaving the option of monotherapy, with a preference for certain drugs, as an exception in case of intolerance or contraindication to all csDMARDs. LoE *1a, §1b; LOA 9.2If a bDMARD* or tsDMARD§ has failed, treatment with another bDMARD or a tsDMARD should be considered; if one TNF inhibitor therapy has failed, patients may receive another TNF inhibitor or an agent with another mode of action. A similar recommendation was made in 2013: “If a first bDMARD has failed, patients should be treated with another bDMARD; if a first TNF inhibitor therapy has failed, patients may receive another TNF inhibitor or a biological agent with another mode of action.” The addition in the first part (“or tsDMARD”) was partly needed because tsDMARDs (Jak inhibition) are now included in the earlier recommendations 8 and 9; “first” was deleted, because the Task Force did not decide to distinguish between failure of one or more bDMARDs. However, it must be noted that it is currently neither known if a Jak inhibitor is effective once another one has failed nor established that a new IL-6 receptor inhibitors or inhibitors of the IL-6 ligand are effective if tocilizumab has failed – this is still part of the research agenda. However, we also lack studies exploring if TNF-inhibitors are efficacious and safe after bDMARDs with other modes of action have failed, and also studies investigating switching between these other modes of action. A few members raised the question if the use of csDMARDs should also be considered when bDMARDs had failed, but this suggestion did not find a majority. The Task Force was also clear about its recommendations that any bDMARD, including another TNF-inhibitor, could be used if a TNi-inhibitor has failed. Thus, drugs with the same or with another mode of action are recommended in this situation. This was based on the data of clinical trials including meta-analyses ADDIN REFMGR.CITE <Refman><Cite><Author>Schoels</Author><Year>2012</Year><RecNum>2344</RecNum><IDText>Comparative effectiveness and safety of biological treatment options after tumour necrosis factor alpha inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2344</Ref_ID><Title_Primary>Comparative effectiveness and safety of biological treatment options after tumour necrosis factor alpha inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis</Title_Primary><Authors_Primary>Schoels,M.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>Wong,J.B.</Authors_Primary><Date_Primary>2012/8</Date_Primary><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>Biological Agents</Keywords><Keywords>Hand</Keywords><Keywords>Infection</Keywords><Keywords>Medline</Keywords><Keywords>methods</Keywords><Keywords>Patients</Keywords><Keywords>Rheumatology</Keywords><Keywords>Risk</Keywords><Keywords>Safety</Keywords><Reprint>Not in File</Reprint><Start_Page>1303</Start_Page><End_Page>1308</End_Page><Periodical>Ann Rheum Dis</Periodical><Volume>71</Volume><Issue>8</Issue><Misc_3>annrheumdis-2011-200490 [pii];10.1136/annrheumdis-2011-200490 [doi]</Misc_3><Address>Correspondence to Monika Schoels, 2 Department of Internal Medicine, Hietzing Hospital, Wolkersbergenstrasse 1, 1130 Vienna, Austria; monika.schoels@chello.at</Address><Web_URL>PM:22294630</Web_URL><ZZ_JournalFull><f name="System">Ann Rheum Dis</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>146 and on the fact that in contrast to registry data, which may be affected by a variety of confounders, several new prospective studies suggest that there is no difference between these two approaches.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlRvcnJlbnRlLVNlZ2FycmE8L0F1dGhvcj48WWVhcj4yMDE2
PC9ZZWFyPjxSZWNOdW0+MzA1MzwvUmVjTnVtPjxJRFRleHQ+VkFSSUFSIFN0dWR5OiBBc3Nlc3Nt
ZW50IG9mIHNob3J0LXRlcm0gZWZmaWNhY3kgYW5kIHNhZmV0eSBvZiByaXR1eGltYWIgY29tcGFy
ZWQgdG8gYW4gdHVtb3IgbmVjcm9zaXMgZmFjdG9yIGFscGhhIGFudGFnb25pc3RzIGFzIHNlY29u
ZC1saW5lIGRydWcgdGhlcmFweSBpbiBwYXRpZW50cyB3aXRoIHJoZXVtYXRvaWQgYXJ0aHJpdGlz
IHJlZnJhY3RvcnkgdG8gYSBmaXJzdCB0dW1vciBuZWNyb3NpcyBmYWN0b3IgYWxwaGEgYW50YWdv
bmlzdDwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9S
ZWZfVHlwZT48UmVmX0lEPjMwNTM8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5WQVJJQVIgU3R1ZHk6
IEFzc2Vzc21lbnQgb2Ygc2hvcnQtdGVybSBlZmZpY2FjeSBhbmQgc2FmZXR5IG9mIHJpdHV4aW1h
YiBjb21wYXJlZCB0byBhbiB0dW1vciBuZWNyb3NpcyBmYWN0b3IgYWxwaGEgYW50YWdvbmlzdHMg
YXMgc2Vjb25kLWxpbmUgZHJ1ZyB0aGVyYXB5IGluIHBhdGllbnRzIHdpdGggcmhldW1hdG9pZCBh
cnRocml0aXMgcmVmcmFjdG9yeSB0byBhIGZpcnN0IHR1bW9yIG5lY3Jvc2lzIGZhY3RvciBhbHBo
YSBhbnRhZ29uaXN0PC9UaXRsZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+VG9ycmVudGUtU2Vn
YXJyYSxWLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QWNvc3RhLFBlcmVpcmEg
QS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1vcmxhLFIuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5SdWl6LEouTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkNsYXZhZ3VlcmEsVC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PkZpZ3VscyxSLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Q29yb21pbmFzLEgu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5HZWxpLEMuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5Sb3NlbGxvLFIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5kZSBBZ3VzdGluLEouSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PkFsZWdyZSxDLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UGVyZXosQy48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkdhcmNpYSxBLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+Um9kcmlndWV6LGRlIGxhIFNlcm5hPC9BdXRob3JzX1ByaW1hcnk+
PERhdGVfUHJpbWFyeT4yMDE2LzEvMjg8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QXJ0aHJpdGlz
PC9LZXl3b3Jkcz48S2V5d29yZHM+ZHJ1ZyB0aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+bWV0
aG9kczwvS2V5d29yZHM+PEtleXdvcmRzPk11bHRpY2VudGVyIFN0dWRpZXM8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdvcmRzPlJpdHV4aW1hYjwvS2V5d29yZHM+
PEtleXdvcmRzPlNhZmV0eTwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcHk8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5UdW1vciBOZWNyb3NpcyBGYWN0b3I8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBG
aWxlPC9SZXByaW50PjxQZXJpb2RpY2FsPlJldW1hdG9sLkNsaW4uPC9QZXJpb2RpY2FsPjxNaXNj
XzM+UzE2OTktMjU4WCgxNSkwMDIxNy1YIFtwaWldOzEwLjEwMTYvai5yZXVtYS4yMDE1LjExLjAx
OSBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPkhvc3BpdGFsIEdlbmVyYWwgSG9zcGl0YWxldC1Nb2lz
ZXMgQnJvZ2dpLCBTYW50IEpvYW4gRGVzcGksIEJhcmNlbG9uYSwgRXNwYW5hLiBFbGVjdHJvbmlj
IGFkZHJlc3M6IHZ0b3JyZW50ZUBoc2pkYmNuLm9yZyYjeEE7SG9zcGl0YWwgU2FudGEgQ3JldSBp
IFNhbnQgUGF1LCBCYXJjZWxvbmEsIEVzcGFuYSYjeEE7SG9zcGl0YWwgZGVsIFZlbmRyZWxsLCBF
bCBWZW5kcmVsbCwgVGFycmFnb25hLCBFc3BhbmEmI3hBO0hvc3BpdGFsIGRlIFZpbGFkZWNhbnMs
IFZpbGFkZWNhbnMsIEJhcmNlbG9uYSwgRXNwYW5hJiN4QTtIb3NwaXRhbCBkZSBQYWxhbW9zLCBQ
YWxhbW9zLCBHaXJvbmEsIEVzcGFuYSYjeEE7SG9zcGl0YWwgR2VuZXJhbCBIb3NwaXRhbGV0LU1v
aXNlcyBCcm9nZ2ksIFNhbnQgSm9hbiBEZXNwaSwgQmFyY2Vsb25hLCBFc3BhbmEmI3hBO0hvc3Bp
dGFsIEdlbmVyYWwgSG9zcGl0YWxldC1Nb2lzZXMgQnJvZ2dpLCBTYW50IEpvYW4gRGVzcGksIEJh
cmNlbG9uYSwgRXNwYW5hJiN4QTtIb3NwaXRhbCBTYW50YSBDcmV1IGkgU2FudCBQYXUsIEJhcmNl
bG9uYSwgRXNwYW5hJiN4QTtIb3NwaXRhbCBkZSBTYW4gSm9yZ2UsIEh1ZXNjYSwgRXNwYW5hJiN4
QTtIb3NwaXRhbCBkZSBsYSBWYWxsIGQmYXBvcztIZWJyb24sIEJhcmNlbG9uYSwgRXNwYW5hJiN4
QTtIb3NwaXRhbCBkZSBsYSBWYWxsIGQmYXBvcztIZWJyb24sIEJhcmNlbG9uYSwgRXNwYW5hJiN4
QTtIb3NwaXRhbCBkZSBNb2xsZXQsIE1vbGxldCBkZWwgVmFsbGVzLCBCYXJjZWxvbmEsIEVzcGFu
YSYjeEE7SG9zcGl0YWwgZGUgVG9ycmV2aWVqYSwgVG9ycmV2aWVqYSwgQWxpY2FudGUsIEVzcGFu
YSYjeEE7SG9zcGl0YWwgU2FudGEgQ3JldSBpIFNhbnQgUGF1LCBCYXJjZWxvbmEsIEVzcGFuYTwv
QWRkcmVzcz48V2ViX1VSTD5QTToyNjgzMTI1NjwvV2ViX1VSTD48WlpfSm91cm5hbFN0ZEFiYnJl
dj48ZiBuYW1lPSJTeXN0ZW0iPlJldW1hdG9sLkNsaW4uPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJl
dj48WlpfV29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0
aG9yPk1hbmRlcnM8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxSZWNOdW0+MzA3MTwvUmVjTnVt
PjxJRFRleHQ+Q29zdC1lZmZlY3RpdmVuZXNzIG9mIGFiYXRhY2VwdCwgcml0dXhpbWFiLCBhbmQg
VE5GaSB0cmVhdG1lbnQgYWZ0ZXIgcHJldmlvdXMgZmFpbHVyZSB3aXRoIFRORmkgdHJlYXRtZW50
IGluIHJoZXVtYXRvaWQgYXJ0aHJpdGlzOiBhIHByYWdtYXRpYyBtdWx0aS1jZW50cmUgcmFuZG9t
aXNlZCB0cmlhbDwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3Vy
bmFsPC9SZWZfVHlwZT48UmVmX0lEPjMwNzE8L1JlZl9JRD48VGl0bGVfUHJpbWFyeT5Db3N0LWVm
ZmVjdGl2ZW5lc3Mgb2YgYWJhdGFjZXB0LCByaXR1eGltYWIsIGFuZCBUTkZpIHRyZWF0bWVudCBh
ZnRlciBwcmV2aW91cyBmYWlsdXJlIHdpdGggVE5GaSB0cmVhdG1lbnQgaW4gcmhldW1hdG9pZCBh
cnRocml0aXM6IGEgcHJhZ21hdGljIG11bHRpLWNlbnRyZSByYW5kb21pc2VkIHRyaWFsPC9UaXRs
ZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TWFuZGVycyxTLkguPC9BdXRob3JzX1ByaW1hcnk+
PEF1dGhvcnNfUHJpbWFyeT5LaWV2aXQsVy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkFkYW5nLEUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5CcnVzLEguTC48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1vZW5zLEguSi48L0F1dGhvcnNfUHJp
bWFyeT48QXV0aG9yc19QcmltYXJ5PkhhcnRrYW1wLEEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5IZW5kcmlrcyxMLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
QnJvdXdlcixFLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+Vmlzc2VyLEguPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Wb25rZW1hbixILkUuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5IZW5kcmlreCxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+SmFuc2VuLFQuTC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
Pldlc3Rob3ZlbnMsUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbiBkZSBM
YWFyLE0uQS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbiBSaWVsLFAuTC48
L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTU8L0RhdGVfUHJpbWFyeT48S2V5d29y
ZHM+QWJhdGFjZXB0PC9LZXl3b3Jkcz48S2V5d29yZHM+YW5hbHlzaXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5hbnRhZ29uaXN0cyAmYW1wOyBpbmhpYml0b3JzPC9LZXl3b3Jkcz48S2V5d29yZHM+QW50
aXJoZXVtYXRpYyBBZ2VudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRz
PjxLZXl3b3Jkcz5BcnRocml0aXMsUmhldW1hdG9pZDwvS2V5d29yZHM+PEtleXdvcmRzPkNvc3Qt
QmVuZWZpdCBBbmFseXNpczwvS2V5d29yZHM+PEtleXdvcmRzPkRpc2Vhc2U8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5EcnVnIFJlc2lzdGFuY2U8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVnIHRoZXJhcHk8
L0tleXdvcmRzPjxLZXl3b3Jkcz5lY29ub21pY3M8L0tleXdvcmRzPjxLZXl3b3Jkcz5GZW1hbGU8
L0tleXdvcmRzPjxLZXl3b3Jkcz5IZWFsdGg8L0tleXdvcmRzPjxLZXl3b3Jkcz5Ib3NwaXRhbHM8
L0tleXdvcmRzPjxLZXl3b3Jkcz5IdW1hbnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5pbW11bm9sb2d5
PC9LZXl3b3Jkcz48S2V5d29yZHM+Sm9pbnRzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5
d29yZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwv
S2V5d29yZHM+PEtleXdvcmRzPk11bHRpY2VudGVyIFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5OZXRoZXJsYW5kczwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5
d29yZHM+UmVzZWFyY2g8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaGV1bWF0aWMgRGlzZWFzZXM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5SaGV1bWF0b2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXR1eGlt
YWI8L0tleXdvcmRzPjxLZXl3b3Jkcz5zZWNvbmRhcnk8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVy
YXBldXRpYyB1c2U8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29y
ZHM+VHJlYXRtZW50IE91dGNvbWU8L0tleXdvcmRzPjxLZXl3b3Jkcz5UdW1vciBOZWNyb3NpcyBG
YWN0b3ItYWxwaGE8L0tleXdvcmRzPjxSZXByaW50Pk5vdCBpbiBGaWxlPC9SZXByaW50PjxTdGFy
dF9QYWdlPjEzNDwvU3RhcnRfUGFnZT48UGVyaW9kaWNhbD5BcnRocml0aXMgUmVzLlRoZXIuPC9Q
ZXJpb2RpY2FsPjxWb2x1bWU+MTc8L1ZvbHVtZT48VXNlcl9EZWZfNT5QTUM0NDg5MDA0PC9Vc2Vy
X0RlZl81PjxNaXNjXzM+MTAuMTE4Ni9zMTMwNzUtMDE1LTA2MzAtNSBbZG9pXTsxMC4xMTg2L3Mx
MzA3NS0wMTUtMDYzMC01IFtwaWldPC9NaXNjXzM+PEFkZHJlc3M+RGVwYXJ0bWVudCBvZiBJUSBI
ZWFsdGhjYXJlLCBSYWRib3VkIEluc3RpdHV0ZSBmb3IgSGVhbHRoIFNjaWVuY2VzLCBSYWRib3Vk
IFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50cmUsIFBvc3RidXMgOTEwMSwgR2VlcnQgR3Jvb3RlcGxl
aW4gTm9vcmQgMjEgKFJvdXRlIDExNCksIDY1MDAgSEIsIE5pam1lZ2VuLCBOZXRoZXJsYW5kcy4g
c29maWUubWFuZGVyc0ByYWRib3VkdW1jLm5sJiN4QTtEZXBhcnRtZW50IG9mIEhlYWx0aCBFdmlk
ZW5jZSwgUmFkYm91ZCBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudHJlLCBOaWptZWdlbiwgTmV0aGVy
bGFuZHMuIHdpZXRza2Uua2lldml0QHJhZGJvdWR1bWMubmwmI3hBO0RlcGFydG1lbnQgb2YgSGVh
bHRoIEV2aWRlbmNlLCBSYWRib3VkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50cmUsIE5pam1lZ2Vu
LCBOZXRoZXJsYW5kcy4gZWRkeS5hZGFuZ0ByYWRib3VkdW1jLm5sJiN4QTtEZXBhcnRtZW50IG9m
IFJoZXVtYXRvbG9neSwgVHdlZVN0ZWRlbiBIb3NwaXRhbCwgRHIuIERlZWxlbmxhYW4gNSwgVGls
YnVyZywgNTA0MiwgQUQsIE5ldGhlcmxhbmRzLiBoYnJ1c0B0c3oubmwmI3hBO0RlcGFydG1lbnQg
b2YgUmhldW1hdG9sb2d5LCBaaWVrZW5odWlzZ3JvZXAgVHdlbnRlLCBaaWx2ZXJtZWV1dyAxLCBB
bG1lbG8sIDc2MDkgUFAsIE5ldGhlcmxhbmRzLiBoLm1vZW5zQHpndC5ubCYjeEE7RGVwYXJ0bWVu
dCBvZiBSaGV1bWF0b2xvZ3ksIEplcm9lbiBCb3NjaCBIb3NwaXRhbCwgSGVucmkgRHVuYW50c3Ry
YWF0IDEsICZhcG9zO3MtSGVydG9nZW5ib3NjaCwgNTIyMywgR1osIE5ldGhlcmxhbmRzLiBhLmhh
cnRrYW1wQGpiei5ubCYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIE1lZGljYWwgQ2Vu
dHJlIExlZXV3YXJkZW4sIEhlbnJpIER1bmFudHdlZyAyLCBMZWV1d2FyZGVuLCA4OTM0LCBBRCwg
TmV0aGVybGFuZHMuIGwuaGVuZHJpa3NAem5iLm5sJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRv
bG9neSwgVW5pdmVyc2l0eSBNZWRpY2FsIENlbnRyZSBHcm9uaW5nZW4sIEhhbnplcGxlaW4gMSwg
R3JvbmluZ2VuLCA5NzAwLCBSQiwgTmV0aGVybGFuZHMuIGUuYnJvdXdlckB1bWNnLm5sJiN4QTtE
ZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgUmlqbnN0YXRlIEhvc3BpdGFsLCBQb3N0YnVzIDk1
NTUsIEFybmhlbSwgNjgwMCwgVEEsIE5ldGhlcmxhbmRzLiBodmlzc2VyQGFseXNpcy5ubCYjeEE7
RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3kgYW5kIENsaW5pY2FsIEltbXVub2xvZ3ksIE1lZGlz
Y2ggU3BlY3RydW0gVHdlbnRlLCBIYWFrc2JlcmdlcnN0cmFhdCA1NSwgRW5zY2hlZGUsIDc1MTMs
IEVSLCBOZXRoZXJsYW5kcy4gaC52b25rZW1hbkBtc3QubmwmI3hBO0RlcGFydG1lbnQgb2YgUmhl
dW1hdGljIERpc2Vhc2VzLCBSYWRib3VkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50cmUsIE5pam1l
Z2VuLCBOZXRoZXJsYW5kcy4gam9zLmhlbmRyaWt4QHJhZGJvdWR1bWMubmwmI3hBO0RlcGFydG1l
bnQgb2YgUmhldW1hdGljIERpc2Vhc2VzLCBSYWRib3VkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50
cmUsIE5pam1lZ2VuLCBOZXRoZXJsYW5kcy4gdGltLmphbnNlbkByYWRib3VkdW1jLm5sJiN4QTtT
a2VsZXRhbCBCaW9sb2d5IGFuZCBFbmdpbmVlcmluZyBSZXNlYXJjaCBDZW50cmUsIERlcGFydG1l
bnQgb2YgRGV2ZWxvcG1lbnQgYW5kIFJlZ2VuZXJhdGlvbiwgS1UgTGV1dmVuLCBPdWRlIE1hcmt0
IDEzLCBMZXV2ZW4sIDMwMDAsIEJlbGdpdW0uIHJlbmUud2VzdGhvdmVuc0B1emxldXZlbi5iZSYj
eEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFVuaXZlcnNpdHkgSG9zcGl0YWxzIExldXZl
biwgT3VkZSBNYXJrdCAxMywgTGV1dmVuLCAzMDAwLCBCZWxnaXVtLiByZW5lLndlc3Rob3ZlbnNA
dXpsZXV2ZW4uYmUmI3hBO0RlcGFydG1lbnQgb2YgUmhldW1hdG9sb2d5IGFuZCBDbGluaWNhbCBJ
bW11bm9sb2d5LCBNZWRpc2NoIFNwZWN0cnVtIFR3ZW50ZSwgSGFha3NiZXJnZXJzdHJhYXQgNTUs
IEVuc2NoZWRlLCA3NTEzLCBFUiwgTmV0aGVybGFuZHMuIG0udmFuZGVsYWFyQG1zdC5ubCYjeEE7
RGVwYXJ0bWVudCBvZiBJUSBIZWFsdGhjYXJlLCBSYWRib3VkIEluc3RpdHV0ZSBmb3IgSGVhbHRo
IFNjaWVuY2VzLCBSYWRib3VkIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50cmUsIFBvc3RidXMgOTEw
MSwgR2VlcnQgR3Jvb3RlcGxlaW4gTm9vcmQgMjEgKFJvdXRlIDExNCksIDY1MDAgSEIsIE5pam1l
Z2VuLCBOZXRoZXJsYW5kcy4gcGlldC52YW5yaWVsQHJhZGJvdWR1bWMubmw8L0FkZHJlc3M+PFdl
Yl9VUkw+UE06MjU5OTc3NDY8L1dlYl9VUkw+PFpaX0pvdXJuYWxTdGRBYmJyZXY+PGYgbmFtZT0i
U3lzdGVtIj5BcnRocml0aXMgUmVzLlRoZXIuPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48Wlpf
V29ya2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1hbj5=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlRvcnJlbnRlLVNlZ2FycmE8L0F1dGhvcj48WWVhcj4yMDE2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=
ADDIN EN.CITE.DATA 165;166 If a second TNFi fails, patients should receive an agent with another mode of action. However, it is self-evident (and supported by the vast majority of the Task Foce members) that a bsDMARD of any of these reference bDMARDs should not be used if the respective boDMARD (or another bsDMARD of the same molecule) has failed to induce sufficient efficacy or vice versa. LoE *1a, §5; LoA 9.2If a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering bDMARDs, especially if this treatment is combined with a csDMARD. This item remained unchanged compared to the 2013 publication. No new data have been published that contest this conclusion. Tapering here means reduction of dose or extension of interval between applications (‘spacing’). It does not necessarily imply cessation of a bDMARD, which may lead to a recurrence of disease in a majority of patients.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkVtZXJ5IFA8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkVtZXJ5IFA8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS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 EN.CITE.DATA 167;168 However, even if treatment is stopped and patients flare, the majority of them (>80%) will recover their previous good outcome upon reinstitution of therapy,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 168;169 and patients should be informed accordingly. This item also indirectly bolsters recommendation #9 on combination therapy of bDMARDs with MTX or another csDMARD, since it implies that bDMARDs should primarily, if not only, be tapered and possibly stopped when combined with a csDMARD, while tapering and stopping of bDMARD monotherapy was not yet sufficiently studied. LoE 2b; LoA 9.0If a patient is in persistent remission, tapering the csDMARD could be considered. The 2013 version of the respective point 13 reads: “In cases of sustained long-term remission, cautious reduction of the csDMARD dose could be considered, as a shared decision between patient and physician”. This item elicited significant discussions, since it would mean leaving patients with RA either without any or with a low dose of a csDMARD. But in general, no new evidence for or against this view has been found over the last years. The overall discussion was somewhat controversial. It was mentioned that here tapering means primarily reducing the dose and that stopping csDMARDs fully may be possible only in exceptional cases. Many rheumatologists on the Task Force panel, though, expressed a view stating that csDMARDs should never be stopped. Consequently, this item received the lowest level of agreement (8.5) of all, although still quite high on the scale of 0 to 10. Of note, the portion worded “as a shared decision between patient and physician” was now deleted. It was felt by the Task Force that mentioning the shared decision for this item among all 12 would imply that the other recommendations may not need to involve the patient, or single out this specific in comparison with all other items and thus offset overarching principle A. Obviously, the removal of this phrase does not mean that shared decision making with the patients is not important, on the contrary: in line with principle A it is of utmost importance for this and for all other recommendations. LoE 4; LoA 8.5The updated recommendations are depicted in an abbreviated way in Figure 1. Part and parcel of this figure are the respective footnotes as well as the accompanying text.DISCUSSIONThe 2016 update of the EULAR RA management recommendations was developed by 50 experts, including patients, rheumatologists and other health care professionals. This was the largest Task Force ever convened for the development of EULAR recommendations, both with respect to the overall number of members and the number of European countries involved, and it is also the first EULAR Task Force with a broad international representation, since rheumatologists from several other continents participated in this activity. This allowed us to also include some views from Asia, and Latin- and North America in the development of the recommendations, an input desired given the information provided in the recent publication of updated ACR and of APLAR recommendations.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxhdTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJlY051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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkxhdTwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJlY051
bT4zMDQ0PC9SZWNOdW0+PElEVGV4dD5BUExBUiByaGV1bWF0b2lkIGFydGhyaXRpcyB0cmVhdG1l
bnQgcmVjb21tZW5kYXRpb25zPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9U
eXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MzA0NDwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5
PkFQTEFSIHJoZXVtYXRvaWQgYXJ0aHJpdGlzIHRyZWF0bWVudCByZWNvbW1lbmRhdGlvbnM8L1Rp
dGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5MYXUsQy5TLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+Q2hpYSxGLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
SGFycmlzb24sQS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkhzaWVoLFQuWS48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkphaW4sUi48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5Pkp1bmcsUy5NLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1By
aW1hcnk+S2lzaGltb3RvLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LdW1h
cixBLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGVvbmcsSy5QLjwvQXV0aG9y
c19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGksWi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkxpY2hhdWNvLEouSi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5
PkxvdXRocmVub28sVy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pkx1byxTLkYu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5OYXNoLFAuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5OZyxDLlQuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5QYXJrLFMuSC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlN1cnlhbmEs
Qi5QLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3V3YW5uYWxhaSxQLjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+V2lqYXlhLEwuSy48L0F1dGhvcnNfUHJpbWFy
eT48QXV0aG9yc19QcmltYXJ5PllhbWFtb3RvLEsuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5ZYW5nLFkuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5ZZWFwLFMu
Uy48L0F1dGhvcnNfUHJpbWFyeT48RGF0ZV9QcmltYXJ5PjIwMTUvOTwvRGF0ZV9QcmltYXJ5PjxL
ZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BdXN0cmFsaWE8L0tleXdvcmRz
PjxLZXl3b3Jkcz5DaGluYTwvS2V5d29yZHM+PEtleXdvcmRzPkhvbmcgS29uZzwvS2V5d29yZHM+
PEtleXdvcmRzPmltbXVub2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5KYXBhbjwvS2V5d29yZHM+
PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+
PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3
b3Jkcz48S2V5d29yZHM+VGFpd2FuPC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVw
cmludD48U3RhcnRfUGFnZT42ODU8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjcxMzwvRW5kX1BhZ2U+
PFBlcmlvZGljYWw+SW50LkouUmhldW0gRGlzPC9QZXJpb2RpY2FsPjxWb2x1bWU+MTg8L1ZvbHVt
ZT48SXNzdWU+NzwvSXNzdWU+PE1pc2NfMz4xMC4xMTExLzE3NTYtMTg1WC4xMjc1NCBbZG9pXTwv
TWlzY18zPjxBZGRyZXNzPkRpdmlzaW9uIG9mIFJoZXVtYXRvbG9neSBhbmQgQ2xpbmljYWwgSW1t
dW5vbG9neSwgUXVlZW4gTWFyeSBIb3NwaXRhbCwgVW5pdmVyc2l0eSBvZiBIb25nIEtvbmcsIEhv
bmcgS29uZyYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIEFsbGVyZ3kgYW5kIEltbXVu
b2xvZ3ksIFRhbiBUb2NrIFNlbmcgSG9zcGl0YWwsIFNpbmdhcG9yZSBDaXR5LCBTaW5nYXBvcmUm
I3hBO0RlcGFydG1lbnQgb2YgTWVkaWNpbmUsIFVuaXZlcnNpdHkgb2YgT3RhZ28gV2VsbGluZ3Rv
biwgV2VsbGluZ3RvbiBTb3V0aCwgTmV3IFplYWxhbmQmI3hBO1NlY3Rpb24gb2YgQWxsZXJneSwg
SW1tdW5vbG9neSBhbmQgUmhldW1hdG9sb2d5LCBhbmQgU2VjdGlvbiBvZiBDbGluaWNhbCBTa2ls
bHMgVHJhaW5pbmcsIFRhaWNodW5nIFZldGVyYW5zIEdlbmVyYWwgSG9zcGl0YWwsIFRhaWNodW5n
LCBUYWl3YW4mI3hBO05hcmF5YW5hIEhvc3BpdGFsLCBKYWlwdXIsIEluZGlhJiN4QTtEaXZpc2lv
biBvZiBSaGV1bWF0b2xvZ3ksIERlcGFydG1lbnQgb2YgSW50ZXJuYWwgTWVkaWNpbmUsIFRoZSBD
YXRob2xpYyBVbml2ZXJzaXR5IG9mIEtvcmVhLCBTdC4gTWFyeSZhcG9zO3MgSG9zcGl0YWwsIFNl
b3VsLCBTb3V0aCBLb3JlYSYjeEE7SW1tdW5vLVJoZXVtYXRvbG9neSBDZW50ZXIsIFN0IEx1a2Um
YXBvcztzIEludGVybmF0aW9uYWwgSG9zcGl0YWwsIFRva3lvLCBKYXBhbiYjeEE7RGVwYXJ0bWVu
dCBvZiBSaGV1bWF0b2xvZ3ksIEZvcnRpcyBGbHQuIEx0IFJhamFuIERoYWxsIEhvc3BpdGFsLCBO
ZXcgRGVsaGksIEluZGlhJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgQWxsZXJneSBh
bmQgSW1tdW5vbG9neSwgVGFuIFRvY2sgU2VuZyBIb3NwaXRhbCwgU2luZ2Fwb3JlIENpdHksIFNp
bmdhcG9yZSYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFBla2luZyBVbml2ZXJzaXR5
IFBlb3BsZSZhcG9zO3MgSG9zcGl0YWwsIEJlaWppbmcsIENoaW5hJiN4QTtTdC4gTHVrZSZhcG9z
O3MgTWVkaWNhbCBDZW50ZXIsIFF1ZXpvbiBDaXR5LCBQaGlsaXBwaW5lcyYjeEE7RGl2aXNpb24g
b2YgUmhldW1hdG9sb2d5LCBEZXBhcnRtZW50IG9mIEludGVybmFsIE1lZGljaW5lLCBGYWN1bHR5
IG9mIE1lZGljaW5lLCBDaGlhbmcgTWFpIFVuaXZlcnNpdHksIENoaWFuZyBNYWksIFRoYWlsYW5k
JiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgQWxsZXJneSBhbmQgSW1tdW5vbG9neSwg
Q2hhbmcgR3VuZyBNZW1vcmlhbCBIb3NwaXRhbCBhbmQgQ2hhbmcgR3VuZyBVbml2ZXJzaXR5LCBU
YW8tWXVhbiwgVGFpd2FuJiN4QTtEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9m
IFF1ZWVuc2xhbmQsIEJyaXNiYW5lLCBRdWVlbnNsYW5kLCBBdXN0cmFsaWEmI3hBO0RlcGFydG1l
bnQgb2YgUmhldW1hdG9sb2d5IGFuZCBJbW11bm9sb2d5LCBTaW5nYXBvcmUgR2VuZXJhbCBIb3Nw
aXRhbCwgU2luZ2Fwb3JlIENpdHksIFNpbmdhcG9yZSYjeEE7RGl2aXNpb24gb2YgUmhldW1hdG9s
b2d5LCBEZXBhcnRtZW50IG9mIEludGVybmFsIE1lZGljaW5lLCBUaGUgQ2F0aG9saWMgVW5pdmVy
c2l0eSBvZiBLb3JlYSwgU3QuIE1hcnkmYXBvcztzIEhvc3BpdGFsLCBTZW91bCwgU291dGggS29y
ZWEmI3hBO1JoZXVtYXRvbG9neSBEaXZpc2lvbiwgRGVwYXJ0bWVudCBvZiBJbnRlcm5hbCBNZWRp
Y2luZSwgQnJhd2lqYXlhIFVuaXZlcnNpdHksIFNhaWZ1bCBBbndhciBHZW5lcmFsIEhvc3BpdGFs
LCBNYWxhbmcsIEluZG9uZXNpYSYjeEE7QWxsZXJneSwgSW1tdW5vbG9neSBhbmQgUmhldW1hdG9s
b2d5IERpdmlzaW9uLCBJbnRlcm5hbCBNZWRpY2luZSBEZXBhcnRtZW50LCBGYWN1bHR5IG9mIE1l
ZGljaW5lLCBSYW1hdGhpYm9kaSBIb3NwaXRhbCwgTWFoaWRvbCBVbml2ZXJzaXR5LCBCYW5na29r
LCBUaGFpbGFuZCYjeEE7RGl2aXNpb24gb2YgUmhldW1hdG9sb2d5LCBEZXBhcnRtZW50IG9mIElu
dGVybmFsIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIEluZG9uZXNpYSwgSmFrYXJ0YSwgSW5kb25l
c2lhJiN4QTtEZXBhcnRtZW50IG9mIEFsbGVyZ3kgYW5kIFJoZXVtYXRvbG9neSwgR3JhZHVhdGUg
U2Nob29sIG9mIE1lZGljaW5lLCBUaGUgVW5pdmVyc2l0eSBvZiBUb2t5bywgVG9reW8sIEphcGFu
JiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgUGVraW5nIFVuaXZlcnNpdHkgUGVvcGxl
JmFwb3M7cyBIb3NwaXRhbCwgQmVpamluZywgQ2hpbmEmI3hBO1N1YmFuZyBKYXlhIE1lZGljYWwg
Q2VudHJlLCBTZWxhbmdvciwgTWFsYXlzaWE8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjYzMzQ0NDk8
L1dlYl9VUkw+PFpaX0pvdXJuYWxTdGRBYmJyZXY+PGYgbmFtZT0iU3lzdGVtIj5JbnQuSi5SaGV1
bSBEaXM8L2Y+PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtm
b3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRob3I+U2luZ2g8L0F1dGhvcj48WWVhcj4yMDE2
PC9ZZWFyPjxSZWNOdW0+MzAyNDwvUmVjTnVtPjxJRFRleHQ+MjAxNSBBbWVyaWNhbiBDb2xsZWdl
IG9mIFJoZXVtYXRvbG9neSBHdWlkZWxpbmUgZm9yIHRoZSBUcmVhdG1lbnQgb2YgUmhldW1hdG9p
ZCBBcnRocml0aXM8L0lEVGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91
cm5hbDwvUmVmX1R5cGU+PFJlZl9JRD4zMDI0PC9SZWZfSUQ+PFRpdGxlX1ByaW1hcnk+MjAxNSBB
bWVyaWNhbiBDb2xsZWdlIG9mIFJoZXVtYXRvbG9neSBHdWlkZWxpbmUgZm9yIHRoZSBUcmVhdG1l
bnQgb2YgUmhldW1hdG9pZCBBcnRocml0aXM8L1RpdGxlX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5TaW5naCxKLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TYWFnLEsuRy48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJyaWRnZXMsUy5MLixKci48L0F1dGhv
cnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkFrbCxFLkEuPC9BdXRob3JzX1ByaW1hcnk+PEF1
dGhvcnNfUHJpbWFyeT5CYW5udXJ1LFIuUi48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PlN1bGxpdmFuLE0uQy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlZheXNi
cm90LEUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NY05hdWdodG9uLEMuPC9B
dXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Pc2FuaSxNLjwvQXV0aG9yc19QcmltYXJ5
PjxBdXRob3JzX1ByaW1hcnk+U2htZXJsaW5nLFIuSC48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9y
c19QcmltYXJ5PkN1cnRpcyxKLlIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5G
dXJzdCxELkUuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5QYXJrcyxELjwvQXV0
aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2F2YW5hdWdoLEEuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5PJmFwb3M7RGVsbCxKLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+S2luZyxDLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGVv
bmcsQS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk1hdHRlc29uLEUuTC48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PlNjaG91c2JvZSxKLlQuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5EcmV2bG93LEIuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5HaW5zYmVyZyxTLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
R3JvYmVyLEouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TdCBDbGFpcixFLlcu
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5UaW5kYWxsLEUuPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5NaWxsZXIsQS5TLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+TWNBbGluZG9uLFQuPC9BdXRob3JzX1ByaW1hcnk+PERhdGVfUHJpbWFyeT4y
MDE2LzE8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QXJ0aHJpdGlzPC9LZXl3b3Jkcz48S2V5d29y
ZHM+Q2FsaWZvcm5pYTwvS2V5d29yZHM+PEtleXdvcmRzPkNhbmFkYTwvS2V5d29yZHM+PEtleXdv
cmRzPkNvbW9yYmlkaXR5PC9LZXl3b3Jkcz48S2V5d29yZHM+Q29uc2Vuc3VzPC9LZXl3b3Jkcz48
S2V5d29yZHM+RGVjaXNpb24gTWFraW5nPC9LZXl3b3Jkcz48S2V5d29yZHM+R2x1Y29jb3J0aWNv
aWRzPC9LZXl3b3Jkcz48S2V5d29yZHM+SGVhbHRoPC9LZXl3b3Jkcz48S2V5d29yZHM+SGVhcnQg
RmFpbHVyZTwvS2V5d29yZHM+PEtleXdvcmRzPkluZmVjdGlvbjwvS2V5d29yZHM+PEtleXdvcmRz
Pm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaW5uZXNvdGE8L0tleXdvcmRzPjxLZXl3b3Jk
cz5PbnRhcmlvPC9LZXl3b3Jkcz48S2V5d29yZHM+UGF0aWVudHM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5QaHlzaWNpYW5zPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9sb2d5PC9LZXl3b3Jkcz48
S2V5d29yZHM+dGhlcmFweTwvS2V5d29yZHM+PEtleXdvcmRzPlR1YmVyY3Vsb3NpczwvS2V5d29y
ZHM+PEtleXdvcmRzPlZhY2NpbmVzPC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwvUmVw
cmludD48U3RhcnRfUGFnZT4xPC9TdGFydF9QYWdlPjxFbmRfUGFnZT4yNTwvRW5kX1BhZ2U+PFBl
cmlvZGljYWw+QXJ0aHJpdGlzIENhcmUgUmVzLihIb2Jva2VuLik8L1BlcmlvZGljYWw+PFZvbHVt
ZT42ODwvVm9sdW1lPjxJc3N1ZT4xPC9Jc3N1ZT48TWlzY18zPjEwLjEwMDIvYWNyLjIyNzgzIFtk
b2ldPC9NaXNjXzM+PEFkZHJlc3M+VW5pdmVyc2l0eSBvZiBBbGFiYW1hIGF0IEJpcm1pbmdoYW0m
I3hBO1VuaXZlcnNpdHkgb2YgQWxhYmFtYSBhdCBCaXJtaW5naGFtJiN4QTtVbml2ZXJzaXR5IG9m
IEFsYWJhbWEgYXQgQmlybWluZ2hhbSYjeEE7QW1lcmljYW4gVW5pdmVyc2l0eSBvZiBCZWlydXQs
IEJlaXJ1dCwgTGViYW5vbiwgYW5kIE1jTWFzdGVyIFVuaXZlcnNpdHksIEhhbWlsdG9uLCBPbnRh
cmlvLCBDYW5hZGEmI3hBO1R1ZnRzIE1lZGljYWwgQ2VudGVyLCBCb3N0b24sIE1hc3NhY2h1c2V0
dHMmI3hBO1R1ZnRzIE1lZGljYWwgQ2VudGVyLCBCb3N0b24sIE1hc3NhY2h1c2V0dHMmI3hBO1R1
ZnRzIE1lZGljYWwgQ2VudGVyLCBCb3N0b24sIE1hc3NhY2h1c2V0dHMmI3hBO1R1ZnRzIE1lZGlj
YWwgQ2VudGVyLCBCb3N0b24sIE1hc3NhY2h1c2V0dHMmI3hBO1R1ZnRzIE1lZGljYWwgQ2VudGVy
LCBCb3N0b24sIE1hc3NhY2h1c2V0dHMmI3hBO0JldGggSXNyYWVsIERlYWNvbmVzcyBNZWRpY2Fs
IENlbnRlciwgQm9zdG9uLCBNYXNzYWNodXNldHRzJiN4QTtVbml2ZXJzaXR5IG9mIEFsYWJhbWEg
YXQgQmlybWluZ2hhbSYjeEE7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBMb3MgQW5nZWxlcyYj
eEE7V2FzaGluZ3RvbiBVbml2ZXJzaXR5IFNjaG9vbCBvZiBNZWRpY2luZSwgU3QuIExvdWlzLCBN
aXNzb3VyaSYjeEE7VW5pdmVyc2l0eSBvZiBDYWxpZm9ybmlhLCBTYW4gRGllZ28mI3hBO1VuaXZl
cnNpdHkgb2YgTmVicmFza2EgTWVkaWNhbCBDZW50ZXIsIE9tYWhhJiN4QTtOb3J0aCBNaXNzaXNz
aXBwaSBNZWRpY2FsIENlbnRlciwgVHVwZWxvJiN4QTtIZWFsdGh5IE1vdGl2YXRpb24sIFNhbnRh
IEJhcmJhcmEsIENhbGlmb3JuaWEmI3hBO01heW8gQ2xpbmljLCBSb2NoZXN0ZXIsIE1pbm5lc290
YSYjeEE7VW5pdmVyc2l0eSBvZiBNaW5uZXNvdGEgYW5kIFBhcmsgTmljb2xsZXQgQ2xpbmljLCBT
dC4gTG91aXMgUGFyayYjeEE7Tm9ydGhTaG9yZSBVbml2ZXJzaXR5IEhlYWx0aCBTeXN0ZW0sIEV2
YW5zdG9uLCBJbGxpbm9pcyYjeEE7R2xvYmFsIEhlYWx0aHkgTGl2aW5nIEZvdW5kYXRpb24sIE5l
dyBZb3JrLCBOZXcgWW9yayYjeEE7Tm9ydGhTaG9yZSBVbml2ZXJzaXR5IEhlYWx0aCBTeXN0ZW0s
IEV2YW5zdG9uLCBJbGxpbm9pcyYjeEE7RHVrZSBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBE
dXJoYW0sIE5vcnRoIENhcm9saW5hJiN4QTtSaGV1bWF0b2xvZ3kgQ29uc3VsdGFudHMgb2YgT3Jl
Z29uLCBXZXN0IExpbm4mI3hBO0FtZXJpY2FuIENvbGxlZ2Ugb2YgUmhldW1hdG9sb2d5LCBBdGxh
bnRhLCBHZW9yZ2lhJiN4QTtUdWZ0cyBNZWRpY2FsIENlbnRlciwgQm9zdG9uLCBNYXNzYWNodXNl
dHRzPC9BZGRyZXNzPjxXZWJfVVJMPlBNOjI2NTQ1ODI1PC9XZWJfVVJMPjxaWl9Kb3VybmFsU3Rk
QWJicmV2PjxmIG5hbWU9IlN5c3RlbSI+QXJ0aHJpdGlzIENhcmUgUmVzLihIb2Jva2VuLik8L2Y+
PC9aWl9Kb3VybmFsU3RkQWJicmV2PjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9N
REw+PC9DaXRlPjwvUmVmbWFuPgB=
ADDIN EN.CITE.DATA 17;39The 2016 update presents the hitherto “leanest” EULAR recommendations for RA management. While in 2010 the document comprised of 3 overarching principles and 15 recommendations and in 2013 it contained 3 overarching principles and 14 recommendations, the 2016 update arrived with 4 principles and 12 recommendations. Despite this reduction, in light of a continuously increasing spectrum of therapeutic options and new information on existing agents and therapeutic strategies, this update covers more treatment aspects and is based on a better evidence base than ever before. This is due to the availability of at least partial answers to several of the research questions posed in 2013, such as items 4, 6, 9 and 21,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl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ADDIN EN.CITE.DATA 16 and of many new data on established and novel drugs as well as therapeutic strategies.The Task Force adhered to several principles established in the course of the development of the 2013 update and even in 2010. For example, aside from evidence on efficacy and safety, economic aspects were generally considered in line with respective general specifications.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkhvbGxvd2F5IEs8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkhvbGxvd2F5IEs8L0F1dGhvcj48WWVhcj4yMDExPC9ZZWFy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ADDIN EN.CITE.DATA 45;46 Also, agents that have not yet been approved by regulatory authorities but for which data from phase III trials were available, were considered with the caveat that their use would be only possible upon such approval; this pertains to bsDMARDs, for which the Task Force relies on the stringency of the regulatory processes of EMA and FDA, for new IL-6 inhibitors and for Jak inhibitors, the first of which is currently only licensed in some parts of the world, but data on others became increasingly available. Finally, the Task Force reiterated its previous conclusions on the importance of stratification according to risk factors of adverse RA outcome, PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhc3Rlc2FlZ2VyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhc3Rlc2FlZ2VyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh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ADDIN EN.CITE.DATA 67;142 once an initial therapy has failed.The individual recommendations are not numbered by importance, but rather by a logical sequence: what is the treatment target and how should the patient be followed? What is the most prudent treatment approach once the diagnosis has been made? How can therapeutic success be maximized? Which therapies should follow a first treatment failure (phase I) and under which circumstances? Which agent or type of drug should be preferred in the course of the development of the treatment strategies? Consequently, the first three items, which were either left fully unchanged or were only minimally changed, deal with the time point of starting effective therapy (as soon as the diagnosis is made and thus without any loss of time); with the definition of the treatment target (sustained remission or low disease activity); and with monitoring and the need to reach a significant improvement of disease activity within 3 months and attainment of the targeted state within 6 months. The preferred instruments to be used when following patients have been defined in previous EULAR activitiesPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGE8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkFsZXRhaGE8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFyPjxS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ADDIN EN.CITE.DATA 22;97 and comprise composite measures that include joint counts, such as the DAS28, CDAI and SDAI as well as the ACR/EULAR remission definitions. Of note, instruments weighing acute phase reactants highly, may exaggerate response, especially with IL-6 or Jak inhibitors. The treatment target (stringent remission or low disease activity) continues to be clinically defined, since focusing at ultrasonographic remission has not shown better outcomes compared with targeting clinical low disease activity or stringent remission, but rather induced overtreatment and thus inefficient use of healthcare resources.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRhbGU8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNO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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRhbGU8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNO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==
ADDIN EN.CITE.DATA 170;171 Moreover, no strategy trial is available comparing the use of the serologic multi-biomarker disease activity (MBDA) test with targeting remission using clinical disease activity assessment by a clinical composite measure (with which MBDA correlates anyway); of note, the MBDA test has been reported to improve to a larger extent upon using a bDMARD that directly targets a cytokine compared with one one that targets T-cell co-stimulation, despite similar clinical, functional and radiographic outcomes. ADDIN REFMGR.CITE <Refman><Cite><Author>Fleischmann</Author><Year>2016</Year><RecNum>3142</RecNum><IDText>Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>3142</Ref_ID><Title_Primary>Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab</Title_Primary><Authors_Primary>Fleischmann,R.</Authors_Primary><Authors_Primary>Connolly,S.E.</Authors_Primary><Authors_Primary>Maldonado,M.A.</Authors_Primary><Authors_Primary>Schiff,M.</Authors_Primary><Date_Primary>2016/9</Date_Primary><Keywords>Abatacept</Keywords><Keywords>Adalimumab</Keywords><Keywords>Arthritis</Keywords><Keywords>C-Reactive Protein</Keywords><Keywords>Decision Making</Keywords><Keywords>Disease</Keywords><Keywords>Joints</Keywords><Keywords>methods</Keywords><Keywords>Methotrexate</Keywords><Keywords>Patients</Keywords><Keywords>Texas</Keywords><Reprint>Not in File</Reprint><Start_Page>2083</Start_Page><End_Page>2089</End_Page><Periodical>Arthritis Rheumatol</Periodical><Volume>68</Volume><Issue>9</Issue><Misc_3>10.1002/art.39714 [doi]</Misc_3><Address>University of Texas Southwestern Medical Center, Dallas
Bristol-Myers Squibb, Princeton, New Jersey
Bristol-Myers Squibb, Princeton, New Jersey
University of Colorado, Denver</Address><Web_URL>PM:27111089</Web_URL><ZZ_JournalStdAbbrev><f name="System">Arthritis Rheumatol</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>172 Moreover, it must be assumed that such test would falsely indicate high disease activity when an infection occurs. For all these reasons, the Task Force recommends to follow patients in clinical practice using a composite measure which comprises joint counts and may include an acute phase reactant. This clinical assessment is pertinent for every therapeutic phase (Figure 1). Subsequent recommendations, however, have undergone some significant changes compared with the 2013 update. While MTX (or in the presence of intolerance another csDMARD) continues to be considered the pivotal drug once the RA diagnosis has been made (item 4), it is recommended more strongly than before to escalate MTX to a dose of 25-30mg weekly (with folate supplementation), given further recent insights on the high response rate with such strategy. PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZpc3NlcjwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZpc3NlcjwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJl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ADDIN EN.CITE.DATA 4;104 Moreover, the combination of csDMARDs, as monotherapy, with glucocorticoids (GC) is more strongly suggested than before in light of increasing evidence that this combination is not surpassed by csDMARD combinations, even if they are applied with glucocorticoids, or bDMARDs plus MTX in terms of efficacy and safety.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA 112;133 In the treatment algorithm (Figure 1, phase I), this is reflected by the respective change from “±” to “+” for the addition of glucocorticoids to csDMARDs. The term “low dose” GC has now been replaced by “short-term” GC, given that various modes of application at different doses have shown to be efficacious. Moreover, the most important aspect for reducing the risk of adverse eventPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRpeG9uPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj
TnVtPjMwNzY8L1JlY051bT48SURUZXh0PkltbWVkaWF0ZSBhbmQgZGVsYXllZCBpbXBhY3Qgb2Yg
b3JhbCBnbHVjb2NvcnRpY29pZCB0aGVyYXB5IG9uIHJpc2sgb2Ygc2VyaW91cyBpbmZlY3Rpb24g
aW4gb2xkZXIgcGF0aWVudHMgd2l0aCByaGV1bWF0b2lkIGFydGhyaXRpczogYSBuZXN0ZWQgY2Fz
ZS1jb250cm9sIGFuYWx5c2lzPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9U
eXBlPkpvdXJuYWw8L1JlZl9UeXBlPjxSZWZfSUQ+MzA3NjwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5
PkltbWVkaWF0ZSBhbmQgZGVsYXllZCBpbXBhY3Qgb2Ygb3JhbCBnbHVjb2NvcnRpY29pZCB0aGVy
YXB5IG9uIHJpc2sgb2Ygc2VyaW91cyBpbmZlY3Rpb24gaW4gb2xkZXIgcGF0aWVudHMgd2l0aCBy
aGV1bWF0b2lkIGFydGhyaXRpczogYSBuZXN0ZWQgY2FzZS1jb250cm9sIGFuYWx5c2lzPC9UaXRs
ZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RGl4b24sVy5HLjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+QWJyYWhhbW93aWN6LE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT5CZWF1Y2hhbXAsTS5FLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+
UmF5LEQuVy48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkJlcm5hdHNreSxTLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+U3Vpc3NhLFMuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT5TeWx2ZXN0cmUsTS5QLjwvQXV0aG9yc19QcmltYXJ5PjxEYXRl
X1ByaW1hcnk+MjAxMi83PC9EYXRlX1ByaW1hcnk+PEtleXdvcmRzPkFkbWluaXN0cmF0aW9uLE9y
YWw8L0tleXdvcmRzPjxLZXl3b3Jkcz5hZHZlcnNlIGVmZmVjdHM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5BZ2VkPC9LZXl3b3Jkcz48S2V5d29yZHM+YW5hbHlzaXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5B
bnRpcmhldW1hdGljIEFnZW50czwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwvS2V5d29y
ZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29yZHM+Q2Fu
YWRhPC9LZXl3b3Jkcz48S2V5d29yZHM+Q2FzZS1Db250cm9sIFN0dWRpZXM8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5jaGVtaWNhbGx5IGluZHVjZWQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5Db21vcmJpZGl0
eTwvS2V5d29yZHM+PEtleXdvcmRzPmNvbXBsaWNhdGlvbnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5E
b3NlLVJlc3BvbnNlIFJlbGF0aW9uc2hpcCxEcnVnPC9LZXl3b3Jkcz48S2V5d29yZHM+ZHJ1ZyB0
aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+ZXBpZGVtaW9sb2d5PC9LZXl3b3Jkcz48S2V5d29y
ZHM+RmVtYWxlPC9LZXl3b3Jkcz48S2V5d29yZHM+R2x1Y29jb3J0aWNvaWRzPC9LZXl3b3Jkcz48
S2V5d29yZHM+SGVhbHRoPC9LZXl3b3Jkcz48S2V5d29yZHM+SHVtYW5zPC9LZXl3b3Jkcz48S2V5
d29yZHM+SW5mZWN0aW9uPC9LZXl3b3Jkcz48S2V5d29yZHM+TWFsZTwvS2V5d29yZHM+PEtleXdv
cmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5PZGRzIFJhdGlvPC9LZXl3b3Jkcz48S2V5
d29yZHM+UGF0aWVudHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5QcmVkbmlzb2xvbmU8L0tleXdvcmRz
PjxLZXl3b3Jkcz5RdWViZWM8L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+
PEtleXdvcmRzPlJpc2s8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrIEFzc2Vzc21lbnQ8L0tleXdv
cmRzPjxLZXl3b3Jkcz5SaXNrIEZhY3RvcnM8L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXB5PC9L
ZXl3b3Jkcz48S2V5d29yZHM+VGltZSBGYWN0b3JzPC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4g
RmlsZTwvUmVwcmludD48U3RhcnRfUGFnZT4xMTI4PC9TdGFydF9QYWdlPjxFbmRfUGFnZT4xMTMz
PC9FbmRfUGFnZT48UGVyaW9kaWNhbD5Bbm4gUmhldW0gRGlzPC9QZXJpb2RpY2FsPjxWb2x1bWU+
NzE8L1ZvbHVtZT48SXNzdWU+NzwvSXNzdWU+PFVzZXJfRGVmXzU+UE1DMzM3NTU4NDwvVXNlcl9E
ZWZfNT48TWlzY18zPmFubnJoZXVtZGlzLTIwMTEtMjAwNzAyIFtwaWldOzEwLjExMzYvYW5ucmhl
dW1kaXMtMjAxMS0yMDA3MDIgW2RvaV08L01pc2NfMz48QWRkcmVzcz5BcnRocml0aXMgUmVzZWFy
Y2ggVUsgRXBpZGVtaW9sb2d5IFVuaXQsIE1hbmNoZXN0ZXIgQWNhZGVtaWMgSGVhbHRoIFNjaWVu
Y2UgQ2VudHJlLCBVbml2ZXJzaXR5IG9mIE1hbmNoZXN0ZXIsIE1hbmNoZXN0ZXIsIFN0b3Bmb3Jk
IEJ1aWxkaW5nLCBNYW5jaGVzdGVyIE0xMyA5UFQsIFVLLiB3aWxsLmRpeG9uQG1hbmNoZXN0ZXIu
YWMudWs8L0FkZHJlc3M+PFdlYl9VUkw+UE06MjIyNDE5MDI8L1dlYl9VUkw+PFpaX0pvdXJuYWxG
dWxsPjxmIG5hbWU9IlN5c3RlbSI+QW5uIFJoZXVtIERpczwvZj48L1paX0pvdXJuYWxGdWxsPjxa
Wl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+PC9DaXRlPjxDaXRlPjxBdXRob3I+
RGVsIFJpbmNvPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVjTnVtPjMwNjQ8L1JlY051bT48
SURUZXh0PkdsdWNvY29ydGljb2lkIGRvc2UgdGhyZXNob2xkcyBhc3NvY2lhdGVkIHdpdGggYWxs
LWNhdXNlIGFuZCBjYXJkaW92YXNjdWxhciBtb3J0YWxpdHkgaW4gcmhldW1hdG9pZCBhcnRocml0
aXM8L0lEVGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVm
X1R5cGU+PFJlZl9JRD4zMDY0PC9SZWZfSUQ+PFRpdGxlX1ByaW1hcnk+R2x1Y29jb3J0aWNvaWQg
ZG9zZSB0aHJlc2hvbGRzIGFzc29jaWF0ZWQgd2l0aCBhbGwtY2F1c2UgYW5kIGNhcmRpb3Zhc2N1
bGFyIG1vcnRhbGl0eSBpbiByaGV1bWF0b2lkIGFydGhyaXRpczwvVGl0bGVfUHJpbWFyeT48QXV0
aG9yc19QcmltYXJ5PkRlbCBSaW5jbyxJPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFy
eT5CYXR0YWZhcmFubyxELkYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5SZXN0
cmVwbyxKLkYuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Fcmlrc29uLEouTS48
L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkVzY2FsYW50ZSxBLjwvQXV0aG9yc19Q
cmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxNC8yPC9EYXRlX1ByaW1hcnk+PEtleXdvcmRzPkFkdWx0
PC9LZXl3b3Jkcz48S2V5d29yZHM+YWR2ZXJzZSBlZmZlY3RzPC9LZXl3b3Jkcz48S2V5d29yZHM+
QXJ0aHJpdGlzPC9LZXl3b3Jkcz48S2V5d29yZHM+QXJ0aHJpdGlzLFJoZXVtYXRvaWQ8L0tleXdv
cmRzPjxLZXl3b3Jkcz5DYXJkaW92YXNjdWxhciBEaXNlYXNlczwvS2V5d29yZHM+PEtleXdvcmRz
PkRvc2UtUmVzcG9uc2UgUmVsYXRpb25zaGlwLERydWc8L0tleXdvcmRzPjxLZXl3b3Jkcz5kcnVn
IHRoZXJhcHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5GZW1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5H
bHVjb2NvcnRpY29pZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5IZWFsdGg8L0tleXdvcmRzPjxLZXl3
b3Jkcz5IdW1hbnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5JbmNpZGVuY2U8L0tleXdvcmRzPjxLZXl3
b3Jkcz5NYWxlPC9LZXl3b3Jkcz48S2V5d29yZHM+TWF4aW11bSBUb2xlcmF0ZWQgRG9zZTwvS2V5
d29yZHM+PEtleXdvcmRzPm1ldGhvZHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwv
S2V5d29yZHM+PEtleXdvcmRzPk1vcnRhbGl0eTwvS2V5d29yZHM+PEtleXdvcmRzPk11bHRpY2Vu
dGVyIFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5QYXRpZW50czwvS2V5d29yZHM+PEtleXdv
cmRzPlByZWRuaXNvbmU8L0tleXdvcmRzPjxLZXl3b3Jkcz5Qcm9wb3J0aW9uYWwgSGF6YXJkcyBN
b2RlbHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXNlYXJjaDwvS2V5d29yZHM+PEtleXdvcmRzPlJl
dHJvc3BlY3RpdmUgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5
d29yZHM+PEtleXdvcmRzPlJpc2s8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrIEZhY3RvcnM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5TdXJ2aXZhbCBSYXRlPC9LZXl3b3Jkcz48S2V5d29yZHM+VGV4YXM8
L0tleXdvcmRzPjxLZXl3b3Jkcz50aGVyYXBldXRpYyB1c2U8L0tleXdvcmRzPjxSZXByaW50Pk5v
dCBpbiBGaWxlPC9SZXByaW50PjxTdGFydF9QYWdlPjI2NDwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+
MjcyPC9FbmRfUGFnZT48UGVyaW9kaWNhbD5BcnRocml0aXMgUmhldW1hdG9sPC9QZXJpb2RpY2Fs
PjxWb2x1bWU+NjY8L1ZvbHVtZT48SXNzdWU+MjwvSXNzdWU+PE1pc2NfMz4xMC4xMDAyL2FydC4z
ODIxMCBbZG9pXTwvTWlzY18zPjxBZGRyZXNzPlVuaXZlcnNpdHkgb2YgVGV4YXMgSGVhbHRoIFNj
aWVuY2UgQ2VudGVyIGF0LCBTYW4gQW50b25pbzwvQWRkcmVzcz48V2ViX1VSTD48dT5QTToyNDUw
NDc5ODwvdT48L1dlYl9VUkw+PFpaX0pvdXJuYWxTdGRBYmJyZXY+PGYgbmFtZT0iU3lzdGVtIj5B
cnRocml0aXMgUmhldW1hdG9sPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48WlpfV29ya2Zvcm1J
RD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPnZhbiBTaWpsPC9B
dXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVjTnVtPjMwNjU8L1JlY051bT48SURUZXh0PkNvbmZv
dW5kaW5nIGJ5IGluZGljYXRpb24gcHJvYmFibHkgZGlzdG9ydHMgdGhlIHJlbGF0aW9uc2hpcCBi
ZXR3ZWVuIHN0ZXJvaWQgdXNlIGFuZCBjYXJkaW92YXNjdWxhciBkaXNlYXNlIGluIHJoZXVtYXRv
aWQgYXJ0aHJpdGlzOiByZXN1bHRzIGZyb20gYSBwcm9zcGVjdGl2ZSBjb2hvcnQgc3R1ZHk8L0lE
VGV4dD48TURMIFJlZl9UeXBlPSJKb3VybmFsIj48UmVmX1R5cGU+Sm91cm5hbDwvUmVmX1R5cGU+
PFJlZl9JRD4zMDY1PC9SZWZfSUQ+PFRpdGxlX1ByaW1hcnk+Q29uZm91bmRpbmcgYnkgaW5kaWNh
dGlvbiBwcm9iYWJseSBkaXN0b3J0cyB0aGUgcmVsYXRpb25zaGlwIGJldHdlZW4gc3Rlcm9pZCB1
c2UgYW5kIGNhcmRpb3Zhc2N1bGFyIGRpc2Vhc2UgaW4gcmhldW1hdG9pZCBhcnRocml0aXM6IHJl
c3VsdHMgZnJvbSBhIHByb3NwZWN0aXZlIGNvaG9ydCBzdHVkeTwvVGl0bGVfUHJpbWFyeT48QXV0
aG9yc19QcmltYXJ5PnZhbiBTaWpsLEEuTS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19Qcmlt
YXJ5PkJvZXJzLE0uPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5Wb3NrdXlsLEEu
RS48L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5Pk51cm1vaGFtZWQsTS5ULjwvQXV0
aG9yc19QcmltYXJ5PjxEYXRlX1ByaW1hcnk+MjAxNDwvRGF0ZV9QcmltYXJ5PjxLZXl3b3Jkcz5h
ZHZlcnNlIGVmZmVjdHM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BZ2VkPC9LZXl3b3Jkcz48S2V5d29y
ZHM+YW5hbHlzaXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5BcnRocml0aXMsUmhldW1hdG9pZDwvS2V5d29yZHM+PEtleXdvcmRzPkNhcmRpb3Zhc2N1
bGFyIERpc2Vhc2VzPC9LZXl3b3Jkcz48S2V5d29yZHM+Y2hlbWljYWxseSBpbmR1Y2VkPC9LZXl3
b3Jkcz48S2V5d29yZHM+Q29ob3J0IFN0dWRpZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5EaXNlYXNl
PC9LZXl3b3Jkcz48S2V5d29yZHM+ZHJ1ZyB0aGVyYXB5PC9LZXl3b3Jkcz48S2V5d29yZHM+ZXRp
b2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5HbHVjb2NvcnRpY29pZHM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5IdW1hbnM8L0tleXdvcmRzPjxLZXl3b3Jkcz5JbmZsYW1tYXRpb248L0tleXdvcmRzPjxL
ZXl3b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29yZHM+TWlkZGxlIEFnZWQ8L0tleXdvcmRz
PjxLZXl3b3Jkcz5OZXRoZXJsYW5kczwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3
b3Jkcz48S2V5d29yZHM+UHJvc3BlY3RpdmUgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPlJl
dHJvc3BlY3RpdmUgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5
d29yZHM+PEtleXdvcmRzPlJpc2s8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaXNrIEZhY3RvcnM8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5TdGVyb2lkczwvS2V5d29yZHM+PEtleXdvcmRzPnRoZXJhcGV1dGlj
IHVzZTwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+
ZTg3OTY1PC9TdGFydF9QYWdlPjxQZXJpb2RpY2FsPlBMb1MuT25lLjwvUGVyaW9kaWNhbD48Vm9s
dW1lPjk8L1ZvbHVtZT48SXNzdWU+MTwvSXNzdWU+PFVzZXJfRGVmXzU+UE1DMzkwNzU1MTwvVXNl
cl9EZWZfNT48TWlzY18zPjEwLjEzNzEvam91cm5hbC5wb25lLjAwODc5NjUgW2RvaV07UE9ORS1E
LTEzLTQzMzgwIFtwaWldPC9NaXNjXzM+PEFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xv
Z3ksIFZVIFVuaXZlcnNpdHkgTWVkaWNhbCBDZW50ZXIsIEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxh
bmRzJiN4QTtEZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgVlUgVW5pdmVyc2l0eSBNZWRpY2Fs
IENlbnRlciwgQW1zdGVyZGFtLCB0aGUgTmV0aGVybGFuZHMmI3hBO0RlcGFydG1lbnQgb2YgUmhl
dW1hdG9sb2d5LCBWVSBVbml2ZXJzaXR5IE1lZGljYWwgQ2VudGVyLCBBbXN0ZXJkYW0sIHRoZSBO
ZXRoZXJsYW5kcyYjeEE7RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ksIFZVIFVuaXZlcnNpdHkg
TWVkaWNhbCBDZW50ZXIsIEFtc3RlcmRhbSwgdGhlIE5ldGhlcmxhbmRzPC9BZGRyZXNzPjxXZWJf
VVJMPlBNOjI0NDk4MjI5PC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5hbWU9IlN5
c3RlbSI+UExvUy5PbmUuPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48WlpfV29ya2Zvcm1JRD4x
PC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48L1JlZm1hbj5=
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkRpeG9uPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 138;139;173 deemed to be rapid tapering to cessation and low cumulative dose of GC, which was, indeed, the case with these alternative glucocorticoid treatment modalities. In contrast to the 2013 update, csDMARD combination therapy, with or without glucocorticoids, is not anymore an explicit part of the recommendations. This conclusion was based on the accruing evidence that this csDMARD combination therapy may not be superior to MTX monotherapy plus GC, but may be associated with an increase in adverse events.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZlcnNjaHVlcmVuPC9BdXRob3I+PFllYXI+MjAxNTwvWWVh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ADDIN EN.CITE.DATA 112;174 A recent indirect-comparison meta-analysis has suggested a superiority of csDMARD combination vs MTX monotherapy,PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkhhemxld29vZDwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkhhemxld29vZDwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+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ADDIN EN.CITE.DATA 175 Not only was this study at odds with a previous direct-comparison meta-analysisPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkthdGNoYW1hcnQ8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFy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 REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkthdGNoYW1hcnQ8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFy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 EN.CITE.DATA 35;176 and with our own SLRs;PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdhdWpvdXgtVmlhbGE8L0F1dGhvcj48WWVhcj4yMDE0PC9Z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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkdhdWpvdXgtVmlhbGE8L0F1dGhvcj48WWVhcj4yMDE0PC9Z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ADDIN EN.CITE.DATA 35;35;50;177 indirect comparisons should also be considered with reservation since their rigor and value is insufficiently understood to date. Interestingly, using a somewhat different approach and based on an independent SLR, the ACR guideline has arrived at a similar conclusion as presented here and recommends MTX monotherapy as the first DMARD in early or established RA.PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNpbmdoPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNpbmdoPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 17 However, the use of csDMARD combination therapy is not precluded by the new recommendations, rather it is at the discretion of the rheumatologist to apply it in the context of the recommendation on the use of MTX as the first treatment “strategy”. Once phase I has failed to reach the treatment target, either in the presence of bad prognostic markers or in the absence of bad prognostic markers after a second csDMARD strategy has failed, the Task Force recommends to us any bDMARD or, less preferably, a tsDMARD. If phase II as depicted in the algorithm fails to arrive at the treatment target, another bDMARD or a tsDMARD should be used. The Task Force reiterated its position that if a TNF inhibitor fails, another TNF inhibitor -but not a biosimilar of the same molecule!- can be as effective as changing the mode of action. Vice versa, an effective biologic agent should not be switched to a biosimilar of another bDMARD for non-medical reasons. However, important data are missing for some of the drugs; for example, clinical trials did not address the efficacy of a TNF-inhibitor after bDMARDs with other modes of action or a Jak inhibitor have failed. Similar questions arise for the other agents and also for the use of IL-6 inhibitors, such as sarilumab or sirukuab, after tocilizumab has failed (see also research agenda).Early bDMARD treatment, including an induction regimen with subsequent withdrawal of bDMARDs as supported by some strategy trials, was discussed but did not find a majority among the Task Force members. This decision was based on the lack of evidence for superiority of such therapy compared with the use of MTX plus glucocorticoids. Moreover, when placed in the context of a T2T strategy, the initial use of csDMARDs yields equal results in the long-term. Finally the cost-effectiveness of first-line bDMARD therapy, especially in light of the reasons just mentioned, is very poor. The 2016 update of the EULAR recommendations is based on the most recent evidence in the area of RA management and on discussions by a large and broadly international Task Force. The recommendations synthesize the current thinking on approaching RA treatment in a set of overarching principles and recommendations. These have been informed by SLRs on the efficacy and safety of the drugs. The Task Force is convinced that adhering to these recommendations, including shared decision making, defining the treatment target, assessing disease activity regularly with appropriate instruments and applying the sequence of drugs as proposed and in a treat-to-target strategy, will maximize the overall outcome in a vast majority of RA patients. Still, a considerable proportion of patients will not reach the target despite all efforts, and for these patients new drugs will still be needed. Also, new information from research activities on treatment strategies, predictive markers, and others will become available in the near future and will likely necessitate yet another update of the recommendations in about 3 years. Until then we hope that the 2016 update will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.Acknowledgement. The Task Force gratefully acknowledges the financial support by EULAR. Participation in EULAR Task Forces requires a priori declaration of conflicits of interest which has been done by all Task Force members. One Task Force member, who had attended the face-to-face meeting and had participated in all voting processes thereof decided to withdraw from the Task Force subsequently because some of that person’s views had not found a majority during the votings. This withdrawal occurred without casting a vote for the level of agreement with the recommendations.Table 1. Glossary and definitionsPoor prognostic factorsModerate (after csDMARD therapy) to high disease activity according to composite measures ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen</Author><Year>2009</Year><RecNum>1421</RecNum><IDText>Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and TNF-blockade</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>1421</Ref_ID><Title_Primary>Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and TNF-blockade</Title_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>Han,C.</Authors_Primary><Authors_Primary>Van der Heijde,D.M.</Authors_Primary><Authors_Primary>Emery,P.</Authors_Primary><Authors_Primary>Bathon,J.M.</Authors_Primary><Authors_Primary>Keystone,E.</Authors_Primary><Authors_Primary>Maini,R.N.</Authors_Primary><Authors_Primary>Kalden,J.R.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>Baker,D.</Authors_Primary><Authors_Primary>Han,J.</Authors_Primary><Authors_Primary>Bala,M.</Authors_Primary><Authors_Primary>St Clair,E.W.</Authors_Primary><Date_Primary>2009/7/10</Date_Primary><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>methods</Keywords><Keywords>Methotrexate</Keywords><Keywords>Patients</Keywords><Reprint>Not in File</Reprint><Start_Page>823</Start_Page><End_Page>827 [Epub 2008 Jul 1]</End_Page><Periodical>Ann Rheum Dis</Periodical><Volume>68</Volume><Address>Medical University of Vienna, Austria</Address><Web_URL>PM:18593759</Web_URL><ZZ_JournalFull><f name="System">Ann Rheum Dis</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>178High acute phase reactant levelsPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbiBKUzwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNtb2xlbiBKUzwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+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ADDIN EN.CITE.DATA 179;180High swollen joint countsPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MTk5Mjwv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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhbiBkZXIgSGVpamRlPC9BdXRob3I+PFllYXI+MTk5Mjwv
WWVhcj48UmVjTnVtPjExNzI8L1JlY051bT48SURUZXh0PlByb2dub3N0aWMgZmFjdG9ycyBmb3Ig
cmFkaW9ncmFwaGljIGRhbWFnZSBhbmQgcGh5c2ljYWwgZGlzYWJpbGl0eSBpbiBlYXJseSByaGV1
bWF0b2lkIGFydGhyaXRpcy4gQSBwcm9zcGVjdGl2ZSBmb2xsb3ctdXAgc3R1ZHkgb2YgMTQ3IHBh
dGllbnRzPC9JRFRleHQ+PE1ETCBSZWZfVHlwZT0iSm91cm5hbCI+PFJlZl9UeXBlPkpvdXJuYWw8
L1JlZl9UeXBlPjxSZWZfSUQ+MTE3MjwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PlByb2dub3N0aWMg
ZmFjdG9ycyBmb3IgcmFkaW9ncmFwaGljIGRhbWFnZSBhbmQgcGh5c2ljYWwgZGlzYWJpbGl0eSBp
biBlYXJseSByaGV1bWF0b2lkIGFydGhyaXRpcy4gQSBwcm9zcGVjdGl2ZSBmb2xsb3ctdXAgc3R1
ZHkgb2YgMTQ3IHBhdGllbnRzPC9UaXRsZV9QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+VmFuIGRl
ciBIZWlqZGUsRC5NLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIFJpZWws
UC5MLjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuIExlZXV3ZW4sTS5BLjwv
QXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+dmFuICZhcG9zO3QgSG9mLE0uQS48L0F1
dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PnZhbiBSaWpzd2lqayxNLkguPC9BdXRob3Jz
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52YW4gZGUgUHV0dGUsTC5CLjwvQXV0aG9yc19Qcmlt
YXJ5PjxEYXRlX1ByaW1hcnk+MTk5Mi84PC9EYXRlX1ByaW1hcnk+PEtleXdvcmRzPkFkb2xlc2Nl
bnQ8L0tleXdvcmRzPjxLZXl3b3Jkcz5BZHVsdDwvS2V5d29yZHM+PEtleXdvcmRzPkFnZWQ8L0tl
eXdvcmRzPjxLZXl3b3Jkcz5hbmFseXNpczwvS2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpczwv
S2V5d29yZHM+PEtleXdvcmRzPkFydGhyaXRpcyxSaGV1bWF0b2lkPC9LZXl3b3Jkcz48S2V5d29y
ZHM+Qmxvb2QgU2VkaW1lbnRhdGlvbjwvS2V5d29yZHM+PEtleXdvcmRzPkMtUmVhY3RpdmUgUHJv
dGVpbjwvS2V5d29yZHM+PEtleXdvcmRzPmNvbXBsaWNhdGlvbnM8L0tleXdvcmRzPjxLZXl3b3Jk
cz5EaXNhYmxlZCBQZXJzb25zPC9LZXl3b3Jkcz48S2V5d29yZHM+ZXBpZGVtaW9sb2d5PC9LZXl3
b3Jkcz48S2V5d29yZHM+RmVtYWxlPC9LZXl3b3Jkcz48S2V5d29yZHM+Rm9sbG93LVVwIFN0dWRp
ZXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5Gb290PC9LZXl3b3Jkcz48S2V5d29yZHM+SGFuZDwvS2V5
d29yZHM+PEtleXdvcmRzPkhsYS1EcjIgQW50aWdlbjwvS2V5d29yZHM+PEtleXdvcmRzPkhsYS1E
cjQgQW50aWdlbjwvS2V5d29yZHM+PEtleXdvcmRzPkh1bWFuczwvS2V5d29yZHM+PEtleXdvcmRz
Pk1hbGU8L0tleXdvcmRzPjxLZXl3b3Jkcz5NaWRkbGUgQWdlZDwvS2V5d29yZHM+PEtleXdvcmRz
PnBhdGhvbG9neTwvS2V5d29yZHM+PEtleXdvcmRzPlBhdGllbnRzPC9LZXl3b3Jkcz48S2V5d29y
ZHM+UHJvZ25vc2lzPC9LZXl3b3Jkcz48S2V5d29yZHM+UHJvc3BlY3RpdmUgU3R1ZGllczwvS2V5
d29yZHM+PEtleXdvcmRzPlJhZGlhdGlvbiBJbmp1cmllczwvS2V5d29yZHM+PEtleXdvcmRzPnJh
ZGlvZ3JhcGh5PC9LZXl3b3Jkcz48S2V5d29yZHM+UmVncmVzc2lvbiBBbmFseXNpczwvS2V5d29y
ZHM+PEtleXdvcmRzPlJlc2VhcmNoPC9LZXl3b3Jkcz48S2V5d29yZHM+UmhldW1hdG9pZCBGYWN0
b3I8L0tleXdvcmRzPjxLZXl3b3Jkcz5SaGV1bWF0b2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5T
ZXZlcml0eSBvZiBJbGxuZXNzIEluZGV4PC9LZXl3b3Jkcz48UmVwcmludD5Ob3QgaW4gRmlsZTwv
UmVwcmludD48U3RhcnRfUGFnZT41MTk8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjUyNTwvRW5kX1Bh
Z2U+PFBlcmlvZGljYWw+QnIuSiBSaGV1bWF0b2wuPC9QZXJpb2RpY2FsPjxWb2x1bWU+MzE8L1Zv
bHVtZT48SXNzdWU+ODwvSXNzdWU+PEFkZHJlc3M+RGVwYXJ0bWVudCBvZiBSaGV1bWF0b2xvZ3ks
IFVuaXZlcnNpdHkgSG9zcGl0YWwgTmlqbWVnZW4sIFRoZSBOZXRoZXJsYW5kczwvQWRkcmVzcz48
V2ViX1VSTD5QTToxMzg2NTQ4PC9XZWJfVVJMPjxaWl9Kb3VybmFsU3RkQWJicmV2PjxmIG5hbWU9
IlN5c3RlbSI+QnIuSiBSaGV1bWF0b2wuPC9mPjwvWlpfSm91cm5hbFN0ZEFiYnJldj48WlpfV29y
a2Zvcm1JRD4xPC9aWl9Xb3JrZm9ybUlEPjwvTURMPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPnZhbiBM
ZWV1d2VuPC9BdXRob3I+PFllYXI+MTk5NzwvWWVhcj48UmVjTnVtPjI0NDwvUmVjTnVtPjxJRFRl
eHQ+SW5kaXZpZHVhbCByZWxhdGlvbnNoaXAgYmV0d2VlbiBwcm9ncmVzc2lvbiBvZiByYWRpb2xv
Z2ljYWwgZGFtYWdlIGFuZCB0aGUgYWN1dGUgcGhhc2UgcmVzcG9uc2UgaW4gZWFybHkgcmhldW1h
dG9pZCBhcnRocml0aXMuIFRvd2FyZHMgZGV2ZWxvcG1lbnQgb2YgYSBkZWNpc2lvbiBzdXBwb3J0
IHN5c3RlbTwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFs
PC9SZWZfVHlwZT48UmVmX0lEPjI0NDwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PkluZGl2aWR1YWwg
cmVsYXRpb25zaGlwIGJldHdlZW4gcHJvZ3Jlc3Npb24gb2YgcmFkaW9sb2dpY2FsIGRhbWFnZSBh
bmQgdGhlIGFjdXRlIHBoYXNlIHJlc3BvbnNlIGluIGVhcmx5IHJoZXVtYXRvaWQgYXJ0aHJpdGlz
LiBUb3dhcmRzIGRldmVsb3BtZW50IG9mIGEgZGVjaXNpb24gc3VwcG9ydCBzeXN0ZW08L1RpdGxl
X1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52YW4gTGVldXdlbixNLkEuPC9BdXRob3JzX1ByaW1h
cnk+PEF1dGhvcnNfUHJpbWFyeT52YW4gUmlqc3dpamssTS5ILjwvQXV0aG9yc19QcmltYXJ5PjxB
dXRob3JzX1ByaW1hcnk+U2x1aXRlcixXLkouPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT52YW4gUmllbCxQLkwuPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LdXBl
cixJLkguPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT52YW4gZGUgUHV0dGUsTC5C
LjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+UGVweXMsTS5CLjwvQXV0aG9yc19Q
cmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+TGltYnVyZyxQLkMuPC9BdXRob3JzX1ByaW1hcnk+PERh
dGVfUHJpbWFyeT4xOTk3LzE8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QWN1dGUgRGlzZWFzZTwv
S2V5d29yZHM+PEtleXdvcmRzPkFjdXRlLVBoYXNlIFByb3RlaW5zPC9LZXl3b3Jkcz48S2V5d29y
ZHM+YW5hbHlzaXM8L0tleXdvcmRzPjxLZXl3b3Jkcz5BcnRocml0aXM8L0tleXdvcmRzPjxLZXl3
b3Jkcz5BcnRocml0aXMsUmhldW1hdG9pZDwvS2V5d29yZHM+PEtleXdvcmRzPkJsb29kIFNlZGlt
ZW50YXRpb248L0tleXdvcmRzPjxLZXl3b3Jkcz5DLVJlYWN0aXZlIFByb3RlaW48L0tleXdvcmRz
PjxLZXl3b3Jkcz5DYW5hZGE8L0tleXdvcmRzPjxLZXl3b3Jkcz5IYW5kPC9LZXl3b3Jkcz48S2V5
d29yZHM+SHVtYW48L0tleXdvcmRzPjxLZXl3b3Jkcz5tZXRob2RzPC9LZXl3b3Jkcz48S2V5d29y
ZHM+TWlkZGxlIEFnZTwvS2V5d29yZHM+PEtleXdvcmRzPnBoeXNpb2xvZ3k8L0tleXdvcmRzPjxL
ZXl3b3Jkcz5waHlzaW9wYXRob2xvZ3k8L0tleXdvcmRzPjxLZXl3b3Jkcz5QcmVkaWN0aXZlIFZh
bHVlIG9mIFRlc3RzPC9LZXl3b3Jkcz48S2V5d29yZHM+UHJvZ25vc2lzPC9LZXl3b3Jkcz48S2V5
d29yZHM+UHJvc3BlY3RpdmUgU3R1ZGllczwvS2V5d29yZHM+PEtleXdvcmRzPlByb3RlaW5zPC9L
ZXl3b3Jkcz48S2V5d29yZHM+UmFkaWF0aW9uIEluanVyaWVzPC9LZXl3b3Jkcz48S2V5d29yZHM+
cmFkaW9ncmFwaHk8L0tleXdvcmRzPjxLZXl3b3Jkcz5SZXByb2R1Y2liaWxpdHkgb2YgUmVzdWx0
czwvS2V5d29yZHM+PEtleXdvcmRzPlJoZXVtYXRvbG9neTwvS2V5d29yZHM+PEtleXdvcmRzPlN1
cHBvcnQsTm9uLVUuUy5Hb3YmYXBvczt0PC9LZXl3b3Jkcz48S2V5d29yZHM+VGltZTwvS2V5d29y
ZHM+PEtleXdvcmRzPlRpbWUgRmFjdG9yczwvS2V5d29yZHM+PFJlcHJpbnQ+Tm90IGluIEZpbGU8
L1JlcHJpbnQ+PFN0YXJ0X1BhZ2U+MjA8L1N0YXJ0X1BhZ2U+PEVuZF9QYWdlPjI3PC9FbmRfUGFn
ZT48UGVyaW9kaWNhbD5KLlJoZXVtYXRvbC48L1BlcmlvZGljYWw+PFZvbHVtZT4yNDwvVm9sdW1l
PjxJc3N1ZT4xPC9Jc3N1ZT48QWRkcmVzcz5EZXBhcnRtZW50IG9mIFJoZXVtYXRvbG9neSwgVW5p
dmVyc2l0eSBIb3NwaXRhbCwgR3JvbmluZ2VuLCBUaGUgTmV0aGVybGFuZHM8L0FkZHJlc3M+PFdl
Yl9VUkw+UE06OTAwMjAwNjwvV2ViX1VSTD48WlpfSm91cm5hbFN0ZEFiYnJldj48ZiBuYW1lPSJT
eXN0ZW0iPkouUmhldW1hdG9sLjwvZj48L1paX0pvdXJuYWxTdGRBYmJyZXY+PFpaX1dvcmtmb3Jt
SUQ+MTwvWlpfV29ya2Zvcm1JRD48L01ETD48L0NpdGU+PENpdGU+PEF1dGhvcj5TbW9sZW4gSlM8
L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFyPjxSZWNOdW0+ODEwPC9SZWNOdW0+PElEVGV4dD5QcmVk
aWN0b3JzIG9mIGpvaW50IGRhbWFnZSBpbiBwYXRpZW50cyB3aXRoIGVhcmx5IHJoZXVtYXRvaWQg
YXJ0aHJpdGlzIHRyZWF0ZWQgd2l0aCBoaWdoLWRvc2UgbWV0aG90cmV4YXRlIHdpdGhvdXQgb3Ig
d2l0aCBjb25jb21pdGFudCBpbmZsaXhpbWFiLiBSZXN1bHRzIGZyb20gdGhlIEFTUElSRSB0cmlh
bDwvSURUZXh0PjxNREwgUmVmX1R5cGU9IkpvdXJuYWwiPjxSZWZfVHlwZT5Kb3VybmFsPC9SZWZf
VHlwZT48UmVmX0lEPjgxMDwvUmVmX0lEPjxUaXRsZV9QcmltYXJ5PlByZWRpY3RvcnMgb2Ygam9p
bnQgZGFtYWdlIGluIHBhdGllbnRzIHdpdGggZWFybHkgcmhldW1hdG9pZCBhcnRocml0aXMgdHJl
YXRlZCB3aXRoIGhpZ2gtZG9zZSBtZXRob3RyZXhhdGUgd2l0aG91dCBvciB3aXRoIGNvbmNvbWl0
YW50IGluZmxpeGltYWIuIFJlc3VsdHMgZnJvbSB0aGUgQVNQSVJFIHRyaWFsPC9UaXRsZV9Qcmlt
YXJ5PjxBdXRob3JzX1ByaW1hcnk+U21vbGVuIEpTPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNf
UHJpbWFyeT52YW4gZGVyIEhlaWpkZSBETUZNPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJp
bWFyeT5TdC5DbGFpciBFVzwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+RW1lcnkg
UDwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QmF0aG9uIEpNPC9BdXRob3JzX1By
aW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5LZXlzdG9uZSBFPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhv
cnNfUHJpbWFyeT5NYWluaSBSTjwvQXV0aG9yc19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+S2Fs
ZGVuIEpSPC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5TY2hpZmYgTTwvQXV0aG9y
c19QcmltYXJ5PjxBdXRob3JzX1ByaW1hcnk+QmFrZXIgRDwvQXV0aG9yc19QcmltYXJ5PjxBdXRo
b3JzX1ByaW1hcnk+SGFuIEM8L0F1dGhvcnNfUHJpbWFyeT48QXV0aG9yc19QcmltYXJ5PkhhbiBK
PC9BdXRob3JzX1ByaW1hcnk+PEF1dGhvcnNfUHJpbWFyeT5CYWxhIE08L0F1dGhvcnNfUHJpbWFy
eT48RGF0ZV9QcmltYXJ5PjIwMDY8L0RhdGVfUHJpbWFyeT48S2V5d29yZHM+QXJ0aHJpdGlzPC9L
ZXl3b3Jkcz48S2V5d29yZHM+TWV0aG90cmV4YXRlPC9LZXl3b3Jkcz48UmVwcmludD5JbiBGaWxl
PC9SZXByaW50PjxTdGFydF9QYWdlPjcwMjwvU3RhcnRfUGFnZT48RW5kX1BhZ2U+NzEwPC9FbmRf
UGFnZT48UGVyaW9kaWNhbD5BcnRocml0aXMgUmhldW08L1BlcmlvZGljYWw+PFZvbHVtZT41NDwv
Vm9sdW1lPjxaWl9Kb3VybmFsRnVsbD48ZiBuYW1lPSJTeXN0ZW0iPkFydGhyaXRpcyBSaGV1bTwv
Zj48L1paX0pvdXJuYWxGdWxsPjxaWl9Xb3JrZm9ybUlEPjE8L1paX1dvcmtmb3JtSUQ+PC9NREw+
PC9DaXRlPjwvUmVmbWFuPm==
ADDIN EN.CITE.DATA 179-181Presence of RF and/or ACPA, especially at high levelsPFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNjb3R0PC9BdXRob3I+PFllYXI+MTk4NzwvWWVhcj48UmVj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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlNjb3R0PC9BdXRob3I+PFllYXI+MTk4NzwvWWVhcj48UmVj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ADDIN EN.CITE.DATA 179;182Combinations of the abovePFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhc3Rlc2FlZ2VyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPlZhc3Rlc2FlZ2VyPC9BdXRob3I+PFllYXI+MjAwOTwvWWVh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ADDIN EN.CITE.DATA 67;142Presence of early erosions ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen JS</Author><Year>2006</Year><RecNum>810</RecNum><IDText>Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate without or with concomitant infliximab. Results from the ASPIRE trial</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>810</Ref_ID><Title_Primary>Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate without or with concomitant infliximab. Results from the ASPIRE trial</Title_Primary><Authors_Primary>Smolen JS</Authors_Primary><Authors_Primary>van der Heijde DMFM</Authors_Primary><Authors_Primary>St.Clair EW</Authors_Primary><Authors_Primary>Emery P</Authors_Primary><Authors_Primary>Bathon JM</Authors_Primary><Authors_Primary>Keystone E</Authors_Primary><Authors_Primary>Maini RN</Authors_Primary><Authors_Primary>Kalden JR</Authors_Primary><Authors_Primary>Schiff M</Authors_Primary><Authors_Primary>Baker D</Authors_Primary><Authors_Primary>Han C</Authors_Primary><Authors_Primary>Han J</Authors_Primary><Authors_Primary>Bala M</Authors_Primary><Date_Primary>2006</Date_Primary><Keywords>Arthritis</Keywords><Keywords>Methotrexate</Keywords><Reprint>In File</Reprint><Start_Page>702</Start_Page><End_Page>710</End_Page><Periodical>Arthritis Rheum</Periodical><Volume>54</Volume><ZZ_JournalFull><f name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>179Failure of 2 or more csDMARDs ADDIN REFMGR.CITE <Refman><Cite><Author>Kiely</Author><Year>2011</Year><RecNum>2303</RecNum><IDText>Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity--the early RA network (ERAN)</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2303</Ref_ID><Title_Primary>Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity--the early RA network (ERAN)</Title_Primary><Authors_Primary>Kiely,P.</Authors_Primary><Authors_Primary>Walsh,D.</Authors_Primary><Authors_Primary>Williams,R.</Authors_Primary><Authors_Primary>Young,A.</Authors_Primary><Date_Primary>2011/5</Date_Primary><Keywords>antagonists & inhibitors</Keywords><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Arthritis,Rheumatoid</Keywords><Keywords>Case Report</Keywords><Keywords>Cohort Studies</Keywords><Keywords>Disability Evaluation</Keywords><Keywords>Disease</Keywords><Keywords>drug therapy</Keywords><Keywords>Female</Keywords><Keywords>Humans</Keywords><Keywords>Longitudinal Studies</Keywords><Keywords>Male</Keywords><Keywords>methods</Keywords><Keywords>Middle Aged</Keywords><Keywords>Multicenter Studies</Keywords><Keywords>Patients</Keywords><Keywords>Prospective Studies</Keywords><Keywords>Research</Keywords><Keywords>Rheumatology</Keywords><Keywords>Severity of Illness Index</Keywords><Keywords>therapeutic use</Keywords><Keywords>therapy</Keywords><Keywords>Treatment Outcome</Keywords><Keywords>Tumor Necrosis Factor-alpha</Keywords><Reprint>Not in File</Reprint><Start_Page>926</Start_Page><End_Page>931</End_Page><Periodical>Rheumatology.(Oxford)</Periodical><Volume>50</Volume><Issue>5</Issue><Misc_3>keq406 [pii];10.1093/rheumatology/keq406 [doi]</Misc_3><Address>Department of Rheumatology, St. George's Healthcare NHS Trust, London, UK</Address><Web_URL>PM:21169343</Web_URL><ZZ_JournalStdAbbrev><f name="System">Rheumatology.(Oxford)</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>151Low dose glucocorticoid<7.5mg/day (prednisone equivalent)PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkR1cnU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkR1cnU8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNO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ADDIN EN.CITE.DATA 55;134Meanings of treatment reductionTaperingUsually reduction of drug dose or increase of application interval (‘spacing’)May include cessation (tapering to 0), but then only after slow reductionCessation, stoppingStopping of a particular drugDisease activity statesRemissionACR-EULAR Boolean or index-based remission definitionPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZlbHNvbjwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl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ADDIN EN.CITE.DATA 22Low disease activityLow disease activity state according to any of the validated composite disease activity measures that include joint countsPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZyYW5zZW4gSjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZyYW5zZW4gSjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+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==
ADDIN EN.CITE.DATA 183-185Moderate, high disease activityRespective disease activity state according to any of the validated composite disease activity measures that include joint countsPFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZyYW5zZW4gSjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+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==
ADDIN REFMGR.CITE PFJlZm1hbj48Q2l0ZT48QXV0aG9yPkZyYW5zZW4gSjwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+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==
ADDIN EN.CITE.DATA 183-185DMARD nomenclature ADDIN REFMGR.CITE <Refman><Cite><Author>Smolen</Author><Year>2014</Year><RecNum>2744</RecNum><IDText>Proposal for a new nomenclature of disease-modifying antirheumatic drugs</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>2744</Ref_ID><Title_Primary>Proposal for a new nomenclature of disease-modifying antirheumatic drugs</Title_Primary><Authors_Primary>Smolen,J.S.</Authors_Primary><Authors_Primary>van der Heijde,D.</Authors_Primary><Authors_Primary>Machold,K.P.</Authors_Primary><Authors_Primary>Aletaha,D.</Authors_Primary><Authors_Primary>Landewe,R.</Authors_Primary><Date_Primary>2014/1</Date_Primary><Keywords>Antirheumatic Agents</Keywords><Keywords>Arthritis</Keywords><Keywords>Austria</Keywords><Keywords>Disease</Keywords><Keywords>drug therapy</Keywords><Keywords>Gold</Keywords><Keywords>Humans</Keywords><Keywords>Hydroxychloroquine</Keywords><Keywords>Methotrexate</Keywords><Keywords>Molecular Structure</Keywords><Keywords>Rheumatic Diseases</Keywords><Keywords>Rheumatology</Keywords><Keywords>standards</Keywords><Keywords>Sulfasalazine</Keywords><Keywords>Terminology as Topic</Keywords><Reprint>Not in File</Reprint><Start_Page>3</Start_Page><End_Page>5</End_Page><Periodical>Ann Rheum Dis</Periodical><Volume>73</Volume><Issue>1</Issue><Misc_3>annrheumdis-2013-204317 [pii];10.1136/annrheumdis-2013-204317 [doi]</Misc_3><Address>Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, , Vienna , Austria</Address><Web_URL>PM:24072562</Web_URL><ZZ_JournalFull><f name="System">Ann Rheum Dis</f></ZZ_JournalFull><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>12Synthetic DMARDs (sDMARDs)Conventional synthetic DMARDs (csDMARDs)E.g. methotrexate, leflunomide, sulfasalazine, hydroxychloroquineTargeted synthetic DMARDs (tsDMARDs)E.g. tofacitinibBiological DMARDs (bDMARDs)Biological originator DMARDs (boDMARDs)Biosimilar DMARDs (bsDMARDs)Table 2. The 2016 EULAR Updated RecommendationsOverarching PrinciplesATreatment of RA patients should aim at the best care and must be based on a shared decision between the patient and the rheumatologist.BTreatment decisions are based on disease activity and other patient factors, such as progression of structural damage, comorbidities and safety issues.CRheumatologists are the specialists who should primarily care for RA patients.DRA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist.Recommendations 1.Therapy with DMARDs should be started as soon as the diagnosis of RA is made. 2.Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient. 3.Monitoring should be frequent in active disease (every 1–3 months); if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted. 4.MTX should be part of the first treatment strategy. 5.In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the (first) treatment strategy. 6.Short-term glucocorticoids should be considered when initiating or changing csDMARDs, in different dose regimens and routes of administration, but should be tapered as rapidly as clinically feasible. 7.If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors, other csDMARDs should be considered. 8.If the treatment target is not achieved with the first csDMARD strategy, when poor prognostic factors are present, addition of a bDMARD*1,2 or a tsDMARD*3 should be considered; current practice would be to start a bDMARD§. 9.bDMARDs*1,2 and tsDMARDs*3 should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and tsDMARDs may have some advantages compared to other bDMARDs.10.If a bDMARD* or tsDMARD? has failed, treatment with another bDMARD or a tsDMARD should be considered; if one TNF inhibitor therapy has failed, patients may receive another TNF inhibitor or an agent with another mode of action.11.If a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering bDMARDs, especially if this treatment is combined with a csDMARD.12.If a patient is in persistent remission, tapering the csDMARD could be considered.DMARDs, disease modifying antirheumatic drugs; boDMARDs, biological originator DMARDs; bsDMARD, biosimilar DMARDs; csDMARDs, conventional synthetic DMARDs; tsDMARDs, targeted synthetic DMARDs1TNF-inhibitors: adalimumab, certolizumab pegol, etanercept, golimumb, infliximab boDMARDs or the respective EMA/FDA approved biosimilars; 2abatacept, rituximab (as first bDMARD under special circumstances – see text), or tocilizumab or respective FDA/EMA approved biosimilars, as well as other IL-6 pathway inhibitors, sarilumab and/or sirukumab, once approved. 3Jak-inhibitors (where approved)*,§,#These symbols indicate different levels of evidence which are correspondingly provided together with voting results and levels of agreement in Table3.Table 3. Evidence levels, voting results and agreement LoESoRFinal vote (%)Level of Agree-ment (0-10)An.a.n.a.1009.9Bn.a.n.a.1009.9Cn.a.n.a.1009.8Dn.a.n.a. 989.7 1.1aA 969.9 2.1aA 919.6 3.2b1009.5 4.1aA 719.8 5.1aA 859.0 6.1aA 988.7 7.5D 948.5 8.*1b§5*A§D 969.0 9.*1a#1b *A#A 969.210.*1a?5A*?D 719.111.2bB 869.012.4C 868.5*,§,#These symbols relate to the corresponding symbols in the recommendations (Table 2), showing the respective levels of evidence.BOX: Research AgendaHow does MTX monotherapy in combination with glucocorticoids compare to monotherapies of sulfasalazine or leflunomide in combination with glucocorticoids, at the doses of csDMARDs as used today?In what proportion of patients is an induction therapy with a bDMARD+MTX with subsequent cessation of the bDMARD effective in inducing sustained remission? Is the application of a TNF-inhibitor after abatacept, tocilizumab, rituximab or a Jak inhibitor has failed, safe and efficacious?How safe and efficacious are abatacept, tocilizumab, rituximab after any of the other non-TNFi-bDMARDs or a tsDMARD has failed? How safe and efficacious is the use of an IL-6 pathway inhibitor if another one has failed?How safe and efficacious is the use of a Jak-inhibitor after another one has failed?Is the risk stratification as recommended by EULAR after failure of MTX improving outcome in those with risk factors and not harming those without bad prognostic markers? Do patients who lack bad prognostic factors benefit as much from a switch or addition of a csDMARD as from the addition of a bDMARD?Can we find predictors of differential response to the different bDMARDs and tsDMARDs?When starting a DMARD, how can we best predict who will attain the treatment target (remission or low disease activity) and who not?Can we predict who will maintain remission after withdrawal a bDMARD?Is tapering of bDMARD monotherapy, where potentially indicated, comparable with bDMARD tapering in the presence of csDMARDs?How good is patient adherence to a bDMARD or tsDMARD and can non-adherence explain secondary loss of efficacy?Is measurement of serum drug or anti-drug antibody levels useful in clinical practice?Which biomarkers will help to find better predictors of bad outcome or response and which have failed in the numerous clinical trials that evaluated gene-expression and other biomarkers?Is the use of telemedicine or e-medicine approaches as effective as direct contact in the clinic for T2T strategies? ADDIN REFMGR.REFLIST Reference List(1) Wilske KR, Healey LA. Challenging the therapeutic pyramid: a new look at treatment strategies for rheumatoid arthritis. J Rheumatol 1990; 17 (Suppl 25):4-7.(2) McCarty DJ. Suppress rheumatoid inflammation early and leave the pyramid to the Egyptians. J Rheumatol 1990; 17:1117-1118.(3) Weinblatt ME. Efficacy of methotrexate in rheumatoid arthritis. Br J Rheumatol 1995; 34 Suppl 2:43-48.(4) Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis 2009; 68(7):1094-1099.(5) Primer on the Rheumatic Diseases. 10th ed. Atlanta, GA: Arthritis Foundation.; 1993.(6) van der Heide A, Jacobs JW, Bijlsma JW, Heurkens AH, Booma-Frankfort C, van der Veen MJ et al. The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial. Ann Intern Med 1996; 124(8):699-707.(7) Huizinga WJ, Machold KP, Breedveld FC, Lipsky PE, Smolen JS. Criteria for early rheumatoid arthritis: From Bayes' law revisited to new thoughts on pathogenesis. (Conference summary). Arthritis Rheum 2002; 46:1155-1159.(8) van der Horst-Bruinsma IE, Speyer I, Visser H, Breedveld FC, Hazes JMW. Diagnosis and course of early onset arthritis: results of a special early arthritis clinic compared to routine patient care. Br J Rheumatol 1998; 37:1084-1088.(9) Emery P, Gough A. Why early arthritis clinics? Br J Rheumatol 1991; 30(4):241-242.(10) Aletaha D, Breedveld FC, Smolen JS. The need for new classification criteria for rheumatoid arthritis. Arthritis Rheum 2005; 52:3333-3336.(11) Emery P, Salmon M. Early rheumatoid arthritis: time to aim for remission? Ann Rheum Dis 1995; 54:944-947.(12) Smolen JS, van der Heijde D, Machold KP, Aletaha D, Landewe R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis 2014; 73(1):3-5.(13) Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016.(14) Aletaha D, Neogi T, Silman A, Funovits J, Felson D, Bingham CO III et al. The 2010 American College of Rheumatology / European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis. Ann Rheum Dis 2010; 69:1580-1588.(15) Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016; 75(1):3-15.(16) Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73(3):492-509.(17) Singh JA, Saag KG, Bridges SL, Jr., Akl EA, Bannuru RR, Sullivan MC et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken ) 2016; 68(1):1-25.(18) Van der Heijde DMFM, van't Hof M, van Riel PL, van de Putte LBA. Development of a Disease activity score based on judgement in clinical practice by rheumatologists. J Rheumatol 1993; 20:579-581.(19) Prevoo MLL, van't Hof MA, Kuper HH, van de Putte LBA, van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38:44-48.(20) Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G et al. A Simplified Disease Activity Index for Rheumatoid Arthritis For Use In Clinical Practice. Rheumatology 2003; 42:244-257.(21) Aletaha D, Nell VPK, Stamm T, Uffmann M, Pflugbeil S, Machold K et al. Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: Validation of a clinical activity score. Arthritis Res 2005; 7:R796-R806.(22) Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J et al. American college of rheumatology/european league against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011; 70(3):404-413.(23) Kavanaugh A, Fleischmann RM, Emery P, Kupper H, Redden L, Guerette B et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis 2013; 72(1):64-71.(24) van der Heijde D. Remission by imaging in rheumatoid arthritis: should this be the ultimate goal? Ann Rheum Dis 2012; 71 Suppl 2:i89-i92.(25) Radner H, Smolen JS, Aletaha D. Remission in rheumatoid arthritis: benefit over low disease activity in patient reported outcomes and costs. Arthritis Res Ther 2014; 16(1):R56.(26) Linde L, Sorensen J, Ostergaard M, Horslev-Petersen K, Hetland ML. Does clinical remission lead to normalization of EQ-5D in patients with rheumatoid arthritis and is selection of remission criteria important? J Rheumatol 2010; 37(2):285-290.(27) Provan SA, Semb AG, Hisdal J, Stranden E, Agewall S, Dagfinrud H et al. Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study. Ann Rheum Dis 2011; 70(5):812-817.(28) Thiele K, Huscher D, Bischoff S, Spathling-Mestekemper S, Backhaus M, Aringer M et al. Performance of the 2011 ACR/EULAR preliminary remission criteria compared with DAS28 remission in unselected patients with rheumatoid arthritis. Ann Rheum Dis 2013; 72(7):1194-1199.(29) Bruynesteyn K, Landewe R, van der LS, van der HD. Radiography as primary outcome in rheumatoid arthritis: acceptable sample sizes for trials with 3 months' follow up. Ann Rheum Dis 2004; 63(11):1413-1418.(30) Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 2008; 58(5):1299-1309.(31) Aletaha D, Alasti F, Smolen JS. Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-month time point. Ann Rheum Dis 2015.(32) van der Heijde D, Aletaha D, Carmona L, Edwards CJ, Kvien TK, Kouloumas M et al. 2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis 2015; 74(1):8-13.(33) Ramiro S, Gaujoux-Viala C, Nam JL, Smolen JS, Buch M, Gossec L et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73(3):529-535.(34) Nam JL, Ramiro S, Gaujoux-Viala C, Takase K, Leon-Garcia M, Emery P et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2014; 73(3):516-528.(35) Gaujoux-Viala C, Nam J, Ramiro S, Landewe R, Buch MH, Smolen JS et al. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73(3):510-515.(36) Cardiel MH, Diaz-Borjon A, Vazquez del Mercado EM, Gamez-Nava JI, Barile Fabris LA, Pacheco TC et al. Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis. Reumatol Clin 2014; 10(4):227-240.(37) Wollenhaupt J, Albrecht K, Kruger K, Muller-Ladner U. The new 2012 German recommendations for treating rheumatoid arthritis : differences compared to the European standpoint. Z Rheumatol 2013; 72(1):6-9.(38) Brenol CV, Nava JI, Soriano ER. Proper management of rheumatoid arthritis in Latin America. What the guidelines say? Clin Rheumatol 2015; 34 Suppl 1:S51-S55.(39) Lau CS, Chia F, Harrison A, Hsieh TY, Jain R, Jung SM et al. APLAR rheumatoid arthritis treatment recommendations. Int J Rheum Dis 2015; 18(7):685-713.(40) European Medicines Agency. Guideline on clinical investigation of medicinal products other than NSAIDs for treatment of rheumatoid arthritis. ema europa eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC500187583 pdf 2015.(41) Gaujoux-Viala C, Gossec L, Cantagrel A, Dougados M, Fautrel B, Mariette X et al. Recommendations of the French Society for Rheumatology for managing rheumatoid arthritis. Joint Bone Spine 2014; 81(4):287-297.(42) Bykerk VP, Schieir O, Akhavan P, Hazlewood GS, Cheng CK, Bombardier C. Emerging issues in pharmacological management of rheumatoid arthritis: results of a national needs assessment survey identifying practice variations for the development of Canadian Rheumatology Association clinical practice recommendations. J Rheumatol 2012; 39(8):1555-1558.(43) Dougados M, Betteridge N, Burmester GR, Euller-Ziegler L, Guillemin F, Hirvonen J et al. EULAR standardised operating procedures for the elaboration, evaluation, dissemination, and implementation of recommendations endorsed by the EULAR standing committees. Ann Rheum Dis 2004; 63(9):1172-1176.(44) Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G et al. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ 2010; 182(18):E839-E842.(45) Guyatt GH, Oxman AD, Kunz R, Jaeschke R, Helfand M, Liberati A et al. Incorporating considerations of resources use into grading recommendations. BMJ 2008; 336(7654):1170-1173.(46) Holloway K, van Dijk L. The World Medicines Situation 2011. Rational Use of Medicines. WHO/EMP/MIE/2011.2.2. Geneva: World Health Organzization; 2011.(47) OCEBM Levels of Evidence Working Group, Oxford Centre for Evidence-Based Medicine. The Oxford 2011 Levels of Evidence. 2011. Ref Type: Grant(48) Ramiro S, et al. SLR on safety aspects of DMARDs to inform the EULAR RA management task force. Ann Rheum Dis (submitted) 2016.(49) Nam J, et al. SLR on bDMARDs to inform the EULAR RA management task force. Ann Rheum Dis (submitted) 2016.(50) Chatzidionysiou K. SLR on csDMARDs to inform the EULAR RA management task force 2016. Ann Rheum Dis (submitted) 2016.(51) Peters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis 2010; 69(2):325-331.(52) van der Goes MC, Jacobs JW, Boers M, Andrews T, Blom-Bakkers MA, Buttgereit F et al. Monitoring adverse events of low-dose glucocorticoid therapy: EULAR recommendations for clinical trials and daily practice. Ann Rheum Dis 2010; 69(11):1913-1919.(53) Hoes JN, Jacobs JW, Boers M, Boumpas D, Buttgereit F, Caeyers N et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2007; 66(12):1560-1567.(54) van Assen S., Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2011; 70(3):414-422.(55) Strehl C, Bijlsma JW, De WM, Boers M, Caeyers N, Cutolo M et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis 2016; 75(6):952-957.(56) Baillet A, Gossec L, Carmona L, Wit M, van Eijk-Hustings Y, Bertheussen H et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis 2016; 75(6):965-973.(57) Furst DE, Keystone EC, So AK, Braun J, Breedveld FC, Burmester GR et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. Ann Rheum Dis 2013; 72 Suppl 2:ii2-34.(58) Buch MH, Smolen JS, Betteridge N, Breedveld FC, Burmester G, Dorner T et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 2011; 70(6):909-920.(59) Pereira R, Lago P, Faria R, Torres T. Safety of Anti-TNF Therapies in Immune-Mediated Inflammatory Diseases: Focus on Infections and Malignancy. Drug Dev Res 2015; 76(8):419-427.(60) Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M et al. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Ann Rheum Dis 2013; 72:482-492.(61) Strangfeld A, Eveslage M, Schneider M, Bergerhausen HJ, Klopsch T, Zink A et al. Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient? Ann Rheum Dis 2011; 70(11):1914-1920.(62) Zink A, Manger B, Kaufmann J, Eisterhues C, Krause A, Listing J et al. Evaluation of the RABBIT Risk Score for serious infections. Ann Rheum Dis 2014; 73(9):1673-1676.(63) St Clair E.W., van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004; 50:3432-3443.(64) Klareskog L, van der Heijde D, de Jager JP, Gough A KJ, Malaise M, Martin-Mola E et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004; 363:675-681.(65) Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R et al. The PREMIER study - A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006; 54:26-37.(66) Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet 2014; 383(9914):321-332.(67) Vastesaeger N, Xu S, Aletaha D, St Clair EW, Smolen JS. A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis. Rheumatology (Oxford) 2009; 48(9):1114-1121.(68) Combe B, et al. Update on Early RA management. Ann Rheum Dis (submitted) 2016.(69) Stoffer MA, Smolen JS, Woolf A, Ambrozic A, Bosworth A, Carmona L et al. Development of patient-centred standards of care for rheumatoid arthritis in Europe: the project. Ann Rheum Dis 2014; 73:902-905.(70) Navarro-Compan V, Smolen JS, Huizinga TW, Landewe R, Ferraccioli G, da Silva JA et al. Quality indicators in rheumatoid arthritis: results from the METEOR database. Rheumatology (Oxford) 2015; 54(9):1630-1639.(71) Widdifield J, Bernatsky S, Paterson JM, Thorne JC, Cividino A, Pope J et al. Quality care in seniors with new-onset rheumatoid arthritis: a Canadian perspective. Arthritis Care Res (Hoboken ) 2011; 63(1):53-57.(72) Memel DS, Somerset M. General practitioner and specialist care: the perceptions of people with rheumatoid arthritis. Primary Health Care Research & Development 2003; 4:29-37.(73) Robinson PC, Taylor WJ. Time to treatment in rheumatoid arthritis: factors associated with time to treatment initiation and urgent triage assessment of general practitioner referrals. J Clin Rheumatol 2010; 16(6):267-273.(74) Kyburz D, Gabay C, Michel BA, Finckh A. The long-term impact of early treatment of rheumatoid arthritis on radiographic progression: a population-based cohort study. Rheumatology (Oxford) 2011; 50(6):1106-1110.(75) Feldman DE, Bernatsky S, Houde M, Beauchamp ME, Abrahamowicz M. Early consultation with a rheumatologist for RA: does it reduce subsequent use of orthopaedic surgery? Rheumatology (Oxford) 2013; 52(3):452-459.(76) Nasonov EL, Karateev DE. Does Russia need a treat-to-target initiative? Rheumatology (Oxford) 2015; 54(3):381-382.(77) Dorner T, Strand V, Cornes P, Goncalves J, Gulacsi L, Kay J et al. The changing landscape of biosimilars in rheumatology. Ann Rheum Dis 2016; 75:974-982.(78) Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol 2015; 11(5):276-289.(79) Cader MZ, Filer A, Hazlehurst J, de PP, Buckley CD, Raza K. Performance of the 2010 ACR/EULAR criteria for rheumatoid arthritis: comparison with 1987 ACR criteria in a very early synovitis cohort. Ann Rheum Dis 2011; 70(6):949-955.(80) Radner H, Neogi T, Smolen JS, Aletaha D. Performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: a systematic literature review. Ann Rheum Dis 2014; 73:114-123.(81) van Aken J, Lard LR, leCessie S, Hazes JM, Breedveld FC, Huizinga TW. Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis. Ann Rheum Dis. 63[274], 279. 2004. Ref Type: Journal (Full)(82) Nell V., Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2004; 43:906-914 Epub 2004 Apr 27.(83) Moura CS, Abrahamowicz M, Beauchamp ME, Lacaille D, Wang Y, Boire G et al. Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study. Arthritis Res Ther 2015; 17:197.(84) Machold KP, Landewe R, Smolen JS, Stamm TA, Van der Heijde DM, Verpoort KN et al. The Stop Arthritis Very Early (SAVE) trial, an international multicentre, randomised, double-blind, placebo-controlled trial on glucocorticoids in very early arthritis. Ann Rheum Dis 2010; 69(3):495-502.(85) Verstappen SM, McCoy MJ, Roberts C, Dale NE, Hassell AB, Symmons DP. Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: results of the STIVEA trial. Ann Rheum Dis 2010; 69(3):503-509.(86) Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69(6):964-975.(87) Klarenbeek NB, Guler-Yuksel M, van der Kooij SM, Han KH, Ronday HK, Kerstens PJ et al. The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis 2011; 70(6):1039-1046.(88) Aletaha D, Funovits J, Keystone EC, Smolen JS. Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum 2007; 56(10):3226-3235.(89) Schipper LG, Fransen J, den Broeder AA, van Riel PL. Time to achieve remission determines time to be in remission. Arthritis Res Ther 2010; 12(3):R97.(90) Ranganath VK, Motamedi K, Haavardsholm EA, Maranian P, Elashoff D, McQueen F et al. Comprehensive appraisal of magnetic resonance imaging findings in sustained rheumatoid arthritis remission: a substudy. Arthritis Care Res (Hoboken ) 2015; 67(7):929-939.(91) Sakellariou G, Scire CA, Verstappen SM, Montecucco C, Caporali R. In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis. Ann Rheum Dis 2013; 72(2):245-249.(92) Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med 2016; 374(13):1243-1252.(93) Gabay C, Emery P, van VR, Dikranian A, Alten R, Pavelka K et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 2013; 381(9877):1541-1550.(94) Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute-phase reactants. Arthritis Rheum 2011; 63(1):43-52.(95) Fleischmann R, van der Heijde D, Koenig AS, Pedersen R, Szumski A, Marshall L et al. How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index? Ann Rheum Dis 2014.(96) Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012; 367(6):495-507.(97) Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C et al. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Ann Rheum Dis 2008; 67(10):1360-1364.(98) Curtis JR, Luijtens K, Kavanaugh A. Predicting future response to certolizumab pegol in rheumatoid arthritis patients: features at 12 weeks associated with low disease activity at 1 year. Arthritis Care Res (Hoboken ) 2012; 64(5):658-667.(99) van der Heijde D, Keystone EC, Curtis JR, Landewe RB, Schiff MH, Khanna D et al. Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post-hoc analysis of the RAPID 1 trial. J Rheumatol 2012; 39(7):1326-1333.(100) Smolen JS, Wollenhaupt J, Gomez-Reino JJ, Grassi W, Gaillez C, Poncet C et al. Attainment and characteristics of clinical remission according to the new ACR-EULAR criteria in abatacept-treated patients with early rheumatoid arthritis: new analyses from the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with early erosive rheumatoid arthritis (AGREE). Arthritis Res Ther 2015; 17:157.(101) Li R, Zhao JX, Su Y, He J, Chen LN, Gu F et al. High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial. Medicine (Baltimore) 2016; 95(28):e3968.(102) Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 2002; 359(9313):1173-1177.(103) Wasko MC, Dasgupta A, Hubert H, Fries JF, Ward MM. Propensity-adjusted association of methotrexate with overall survival in rheumatoid arthritis. Arthritis Rheum 2013; 65(2):334-342.(104) Emery P, Bingham CO, III, Burmester GR, Bykerk VP, Furst DE, Mariette X et al. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naive patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study. Ann Rheum Dis 2016.(105) Atsumi T, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y et al. The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Ann Rheum Dis 2016; 75(1):75-83.(106) Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999; 353(9164):1568-1573.(107) O'Dell J. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996; 334:1287-1291.(108) Moreland LW, O'Dell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial. Arthritis Rheum 2012; 64(9):2824-2835.(109) O'Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR et al. Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. N Engl J Med 2013; 369:307-318.(110) van Vollenhoven RF, Geborek P, Forslind K, Albertsson K, Ernestam S, Petersson IF et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet 2012; 379:1712-1720.(111) de Jong PH, Hazes JM, Han HK, Huisman M, van ZD, van der Lubbe PA et al. Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial. Ann Rheum Dis 2014; 73(7):1331-1339.(112) Verschueren P, De CD, Corluy L, Joos R, Langenaken C, Taelman V et al. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis 2015; 74(1):27-34.(113) Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van ZD, Kerstens PJ, Hazes JM et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007; 146(6):406-415.(114) Smolen JS, Aletaha D, Keystone E. Superior efficacy of combination therapy for rheumatoid arthritis. Fact or Fiction? Arthritis Rheum 2005; 52:2975-2983.(115) Landewe RB, Smolen JS, Weinblatt ME, Emery P, Dougados M, Fleischmann R et al. Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example. Ann Rheum Dis 2014; 73(10):1755-1760.(116) Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM et al. 2012 update of the 2008 american college of rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken ) 2012; 64(5):625-639.(117) Combe B, et al. 2016 update of the EULAR recommendations for management of early arthritis. Ann Rheum Dis 2016; submitted.(118) Cutolo M, Bolosiu H, Perdriset G. Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen. Rheumatology (Oxford) 2013; 52(6):1132-1140.(119) Gaujoux-Viala C, Smolen JS, Landewe R, Dougados M, Tore KK, Martin-Mola E et al. Current evidence for the management of rheumatoid arthritis with synthetic disease modifying antirheumatic drugs: A systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010; 69:1004-1009.(120) Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gomor B et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology (Oxford) 2000; 39(6):655-665.(121) G?testam Skorpen C., Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016; [Epub ahead of print].(122) Rau R, Herborn G, Menninger H, Sangha O. Radiographic outcome after three years of patients with early erosive rheumatoid arthritis treated with intramuscular methotrexate or parenteral gold. Extension of a one-year double-blind study in 174 patients. Rheumatology (Oxford) 2002; 41(2):196-204.(123) Lehman AJ, Esdaile JM, Klinkhoff AV, Grant E, Fitzgerald A, Canvin J. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Arthritis Rheum 2005; 52(5):1360-1370.(124) Katz SJ, Russell AS. Re-evaluation of antimalarials in treating rheumatic diseases: re-appreciation and insights into new mechanisms of action. Curr Opin Rheumatol 2011; 23(3):278-281.(125) Hage MP, Al-Badri MR, Azar ST. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role. Ther Adv Endocrinol Metab 2014; 5(4):77-85.(126) Sharma TS, Wasko MC, Tang X, Vedamurthy D, Yan X, Cote J et al. Hydroxychloroquine Use Is Associated With Decreased Incident Cardiovascular Events in Rheumatoid Arthritis Patients. J Am Heart Assoc 2016; 5(1).(127) Van der Heijde DM, van Riel PL, Nuver-Zwart IH, van de Putte LB. Sulphasalazine versus hydroxychloroquine in rheumatoid arthritis: 3- year follow-up. Lancet 1990; 335(8688):539.(128) Strangfeld A, Hierse F, Kekow J, von HU, Tony HP, Dockhorn R et al. Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide. Ann Rheum Dis 2009; 68(12):1856-1862.(129) De Stefano R., Frati E, Nargi F, Baldi C, Menza L, Hammoud M et al. Comparison of combination therapies in the treatment of rheumatoid arthritis: leflunomide-anti-TNF-alpha versus methotrexate-anti-TNF-alpha. Clin Rheumatol 2010; 29(5):517-524.(130) Burmester GR, Mariette X, Montecucco C, Monteagudo-Saez I, Malaise M, Tzioufas AG et al. Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial. Ann Rheum Dis 2007; 66(6):732-739.(131) Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008; 58(10):2968-2980.(132) Goekoop-Ruiterman YP, De Vries-Bouwstra JK, Allaart CF, Van Zeben D, Kerstens PJ, Hazes JM et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial. Arthritis Rheum 2005; 52:3381-3390.(133) Nam JL, Villeneuve E, Hensor EM, Conaghan PG, Keen HI, Buch MH et al. Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study). Ann Rheum Dis 2014; 73(1):75-85.(134) Duru N, van der Goes MC, Jacobs JW, Andrews T, Boers M, Buttgereit F et al. EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2013; 72(12):1905-1913.(135) Buttgereit F, da Silva JA, Boers M, Burmester GR, Cutolo M, Jacobs J et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002; 61(8):718-722.(136) Listing J, Kekow J, Manger B, Burmester GR, Pattloch D, Zink A et al. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Ann Rheum Dis 2015; 74:415-421.(137) Lahiri M, Dixon WG. Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis. Best Pract Res Clin Rheumatol 2015; 29(2):290-305.(138) van Sijl AM, Boers M, Voskuyl AE, Nurmohamed MT. Confounding by indication probably distorts the relationship between steroid use and cardiovascular disease in rheumatoid arthritis: results from a prospective cohort study. PLoS One 2014; 9(1):e87965.(139) Del Rinco I, Battafarano DF, Restrepo JF, Erikson JM, Escalante A. Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol 2014; 66(2):264-272.(140) Choy EH, Kingsley GH, Khoshaba B, Pipitone N, Scott DL. A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs. Ann Rheum Dis 2005; 64(9):1288-1293.(141) Taylor PC, Keystone EC, van der Heijde D, Tanaka Y, Ishii T, Emoto K et al. Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study. [Abstract]. Arthritis Rheum 2015; 67 (Suppl 10):L2. . Accessed January 4, 2016.(142) Visser K, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ronday HK, Seys PE, Kerstens PJ et al. A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: post hoc analyses from the BeSt study. Ann Rheum Dis 2010; 69(7):1333-1337.(143) Yoo DH, Prodanovic N, Jaworski J, Miranda P, Ramiterre E, Lanzon A et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis 2016.(144) Choe JY, Prodanovic N, Niebrzydowski J, Staykov I, Dokoupilova E, Baranauskaite A et al. A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis 2015.(145) Emery P, Vencovsky J, Sylwestrzak A, Leszczynski P, Porawska W, Baranauskaite A et al. A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis 2015.(146) Schoels M, Aletaha D, Smolen JS, Wong JB. Comparative effectiveness and safety of biological treatment options after tumour necrosis factor alpha inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis. Ann Rheum Dis 2012; 71(8):1303-1308.(147) Porter D, van MJ, Dale J, Messow CM, McConnachie A, Walker A et al. Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial. Lancet 2016.(148) Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C et al. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum 2013; 65(1):28-38.(149) Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358(7):676-688.(150) Coleman M, Lammers PE, Ciceri F, Jacobs IA. Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma. Clin Lymphoma Myeloma Leuk 2016; 16(4):175-181.(151) Kiely P, Walsh D, Williams R, Young A. Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity--the early RA network (ERAN). Rheumatology (Oxford) 2011; 50(5):926-931.(152) Emery P, Hammoudeh M, Fitzgerald O, Combe B, Martin-Mola E, Buch MH et al. Sustained remission with etanercept tapering in early rheumatoid arthritis. N Engl J Med 2014; 371(19):1781-1792.(153) Detert J, Bastian H, Listing J, Weiss A, Wassenberg S, Liebhaber A et al. Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naive patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study. Ann Rheum Dis 2013; 72(6):844-850.(154) Bijlsma JW, Welsing PM, Woodworth TG, Middelink LM, Petho-Schramm A, Bernasconi C et al. Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial. Lancet 2016; 388:343-355.(155) Bejarano V, Conaghan PG, Quinn MA, Saleem B, Emery P. Benefits 8 years after a remission induction regime with an infliximab and methotrexate combination in early rheumatoid arthritis. Rheumatology (Oxford) 2010; 49(10):1971-1974.(156) Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Kelman A et al. Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial. Ann Rheum Dis 2015; 75:1081-1091.(157) Kaneko Y, Atsumi T, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K et al. Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study). Ann Rheum Dis 2016.(158) Dougados M, Kissel K, Conaghan PG, Mola EM, Schett G, Gerli R et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis 2014; 73(5):803-809.(159) Fleischmann R, Takeuchi T, Schlichting D, Macias WL, Rooney T, Grubuz S et al. Baricitinib, Methotrexate, or Baricitinib Plus Methotrexate in Patients with Early Rheumatoid Arthritis Who Had Received Limited or No Treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Phase 3 Trial Results [abstract]. Arhritis Rheum 2015; 67 (Suppl 10):. Accessed January 4, 2016.(160) Lee EB, Fleischmann RM, Hall S, van Vollenhoven RF, Bradley J, Gruben D et al. Radiographic, Clinical and Functional Comparison of Tofacitinib Monotherapy Versus Methotrexate in Methotrexate-Nave Patients with Rheumatoid Arthritis. Arthritis Rheum 2012; 64 (Suppl):S1049.(161) Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010; 69(1):88-96; published Online First 17 March 2009.(162) Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barre E et al. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis 2015; 74(1):19-26.(163) Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D, Macfarlane JD et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998; 41(9):1552-1563.(164) Burmester GR, Kivitz AJ, Kupper H, Arulmani U, Florentinus S, Goss SL et al. Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial. Ann Rheum Dis 2015; 74(6):1037-1044.(165) Torrente-Segarra V, Acosta PA, Morla R, Ruiz JM, Clavaguera T, Figuls R et al. VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist. Reumatol Clin 2016.(166) Manders SH, Kievit W, Adang E, Brus HL, Moens HJ, Hartkamp A et al. Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial. Arthritis Res Ther 2015; 17:134.(167) Emery P, Hammoudeh M, Fitzgerald O, Combe B, Martin-Mola E, Bukowski J et al. Assessing maintenance of remission with reduced dose etanercept plus methotrexate, methotrexate alone, or placebo in patients with early rheumatoid arthritis who achieved remission with etanercept and methotrextate: the PRIZE study. Ann Rheum Dis 2013; 72 (Suppl 3):399.(168) Smolen JS, Emery P, Ferraccioli GF, Samborski W, Berenbaum F, Davies OR et al. Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double-blind, randomised, placebo-controlled trial. Ann Rheum Dis 2014.(169) Tanaka Y, Hirata S, Saleem B, Emery P. Discontinuation of biologics in patients with rheumatoid arthritis. Clin Exp Rheumatol 2013; 31 (4Suppl78):522-527.(170) Dale J, Stirling A, Zhang R, Purves D, Foley J, Sambrook M et al. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Ann Rheum Dis 2016; 75(6):1043-1050.(171) Haavardsholm EA, Aga AB, Olsen IC, Lillegraven S, Hammer HB, Uhlig T et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ 2016; 354:i4205.(172) Fleischmann R, Connolly SE, Maldonado MA, Schiff M. Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab. Arthritis Rheumatol 2016; 68(9):2083-2089.(173) Dixon WG, Abrahamowicz M, Beauchamp ME, Ray DW, Bernatsky S, Suissa S et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis 2012; 71(7):1128-1133.(174) Verschueren P, De CD, Corluy L, Joos R, Langenaken C, Taelman V et al. Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial. Ann Rheum Dis 2016.(175) Hazlewood GS, Barnabe C, Tomlinson G, Marshall D, Devoe D, Bombardier C. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ 2016; 353:i1777.(176) Katchamart W, Trudeau J, Phumethum V, Bombardier C. Methotrexate monotherapy versus methotrexate combination therapy with non-biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis. Cochrane Database Syst Rev 2010; 4:CD008495.(177) Gaujoux-Viala C, Smolen JS, Landewe R, Dougados M, Kvien TK, Mola EM et al. Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010; 69(6):1004-1009.(178) Smolen JS, Han C, Van der Heijde DM, Emery P, Bathon JM, Keystone E et al. Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and TNF-blockade. Ann Rheum Dis 2009; 68:823-827 [Epub 2008 Jul 1].(179) Smolen JS, van der Heijde DMFM, St.Clair EW, Emery P, Bathon JM, Keystone E et al. Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate without or with concomitant infliximab. Results from the ASPIRE trial. Arthritis Rheum 2006; 54:702-710.(180) van Leeuwen MA, van Rijswijk MH, Sluiter WJ, van Riel PL, Kuper IH, van de Putte LB et al. Individual relationship between progression of radiological damage and the acute phase response in early rheumatoid arthritis. Towards development of a decision support system. J Rheumatol 1997; 24(1):20-27.(181) Van der Heijde DM, van Riel PL, van Leeuwen MA, van 't Hof MA, van Rijswijk MH, van de Putte LB. Prognostic factors for radiographic damage and physical disability in early rheumatoid arthritis. A prospective follow-up study of 147 patients. Br J Rheumatol 1992; 31(8):519-525.(182) Scott DL, Symmons DP, Coulton BL, Popert AJ. Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1987; 1(8542):1108-1111.(183) Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol 2005; 23:S93-S99.(184) Aletaha D, Ward MM, Machold KP, Nell VPK, Stamm T, Smolen JS. Remission and active disease in rheumatoid arthritis: Defining criteria for disease activity states. Arthritis Rheum 2005; 52:2625-2636.(185) Aletaha D, Smolen JS. The Definition and Measurement of Disease Modification in Inflammatory Rheumatic Diseases. Rheum Dis Clin North Am 2006; 32:9-44. ................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related download
- gout and other crystal arthopathies
- updates in harrison 18th edition paragbawaskar
- imms hemsida har flyttat till ht
- needs statement american medical seminars
- 13 rajiv gandhi university of health sciences
- university of manchester
- accepted for publication in arthritis care and research
- rajiv gandhi university of health sciences
- Българско дружество по ревматология
Related searches
- university of minnesota college of education
- university of minnesota school of social work
- wharton school of the university of pennsylvania
- cost of university of scranton
- university of minnesota school of education
- university of scranton cost of attendance
- university of south florida college of medicine
- university of minnesota masters of social work
- ecampus of university of phoenix
- university of minnesota college of continuing education
- university of illinois college of nursing
- university of north texas college of nursing