Abstract - University of Manchester



The relationship between depression and biologic treatment response in rheumatoid arthritis: An analysis of the British Society for Rheumatology Biologics Register. Faith Matcham, Rebecca Davies2,3, Matthew Hotopf1,4, Kimme Hyrich 2,3, Sam Norton5,6, Sophia Steer6, James Galloway6. King’s College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, London, UK.Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, the University of Manchester, UK. NIHR Manchester Biomedical Research Centre, Central Manchester Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, UK.South London and Maudsley NHS Foundation Trust, Maudsley Hospital, London, UK. King’s College London, Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, London, UK.King’s College London, Department of Academic Rheumatology, London, UK.Correspondence address:Dr Faith Matcham,Institute of Psychiatry, Psychology & Neuroscience, King’s College London,Weston Education Centre,10 Cutcombe road,London SE5 9RJ faith.matcham@kcl.ac.uk(+44) 2078480868AbstractObjectiveTo investigate the relationship between depressive symptoms and treatment response and disease activity over a one-year follow-up.MethodsData from the British Society for Rheumatology Biologics Register were used, representing 18,421 RA patients receiving biologic treatment. Depressive symptoms were identified through one of three assessments: reporting a history of depression; the Medical Outcomes Survey 36-item Short Form (SF36); or the EuroQol (EQ5D). Logistic regression analyses examined the relationship between baseline depressive symptoms and odds of good treatment response by 1-year. Multilevel models addressed the association between baseline depressive symptoms and disease activity outcomes over 1-year follow-up, adjusting for age, gender, disease duration, comorbidities, and baseline disease activity and physical disability. ResultsDepression symptoms at biologic treatment initiation were associated with 20-40% reduced odds of achieving a good treatment response at 1-year. Depressive symptoms at baseline also associated with reduced improvement in disease activity over the course of follow-up. Patients with a history of depression or reporting symptoms of depression according to the EQ5D showed reduced improvement in tender and swollen joints, patient global assessment (PGA) and erythrocyte sedimentation rate (ESR) over 1-year follow-up. Patients with depression symptoms according to the SF36 showed reduced improvement in tender and swollen joints, but not ESR or PGA. ConclusionExperiencing symptoms of depression at the start of biologics treatment may reduce the odds of achieving a good treatment response, and reduce improvement in disease activity over time. Depression should be managed as part of routine clinical care to optimise treatment outcomes. Keywords: Rheumatoid Arthritis, Biological therapies, Depression, Epidemiology, Quality of life, Mental health services, StatisticsIntroductionDepression is prevalent in RA, with meta-analysis evidence suggesting a 17% point prevalence according to diagnostic interview ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket169", "ISSN" : "1462-0332", "PMID" : "24003249", "abstract" : "OBJECTIVE: There is substantial uncertainty regarding the prevalence of depression in RA. We conducted a systematic review aiming to describe the prevalence of depression in RA. METHODS: Web of Science, PsycINFO, CINAHL, Embase, Medline and PubMed were searched for cross-sectional studies reporting a prevalence estimate for depression in adult RA patients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a meta-analysis was performed. RESULTS: A total of 72 studies, including 13,189 patients, were eligible for inclusion in the review. Forty-three methods of defining depression were reported. Meta-analyses revealed the prevalence of major depressive disorder to be 16.8% (95% CI 10%, 24%). According to the PHQ-9, the prevalence of depression was 38.8% (95% CI 34%, 43%), and prevalence levels according to the HADS with thresholds of 8 and 11 were 34.2% (95% CI 25%, 44%) and 14.8% (95% CI 12%, 18%), respectively. The main influence on depression prevalence was the mean age of the sample. CONCLUSION: Depression is highly prevalent in RA and associated with poorer RA outcomes. This suggests that optimal care of RA patients may include the detection and management of depression.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2013", "12", "1" ] ] }, "page" : "2136-48", "title" : "The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[1]", "plainTextFormattedCitation" : "[1]", "previouslyFormattedCitation" : "[1]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1]. Recent evidence has highlighted depression symptoms as a prognostic psychomarker for poor rheumatological outcomes, with symptoms of depression and anxiety associated with worsened disease activity, physical function, and reduced response to Disease Modifying Anti-Rheumatic Drug (DMARD) and glucocorticoid treatments ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kev306", "ISSN" : "1462-0332", "PMID" : "26350486", "abstract" : "OBJECTIVE: The aim of this analysis is to examine the longitudinal impact of symptoms of depression/anxiety on treatment response, long-term disease activity and physical disability in RA. METHODS: Secondary analysis of clinical trial data was performed. Data were collected at baseline and at 6-monthly intervals for 2 years. The EuroQoL (EQ-5D(TM)) indicated depression/anxiety symptom severity. Our primary outcomes of interest were (i) DAS-28 and (ii) physical disability measured via the HAQ. Secondary outcomes were: tender and swollen joint counts, patient global assessment, ESR and odds of reaching clinical remission. Multilevel models were used to assess the impact of baseline and persistent depression/anxiety on outcomes over 2 years. RESULTS: Data from 379 patients were included. After adjusting for covariates, baseline depression/anxiety symptoms were associated with increased DAS-28 outcomes and increased tender joint counts. Persistent depression/anxiety symptoms were associated with increased DAS-28 scores, HAQ scores, tender joint counts and patient global assessment of disease activity, and reduced odds of reaching clinical remission. Patients with symptoms of depression/anxiety at baseline also showed a 50% reduction in prednisolone treatment effect, in comparison with patients with no symptoms of depression/anxiety at baseline. CONCLUSION: Baseline and persistent symptoms of depression/anxiety are associated with poorer health outcomes over time, as well as reduced treatment response. Mental health should be routinely measured both in clinical practice and in research, and managed alongside rheumatological disease to optimize health outcomes. Further research is required to examine whether treatment of mental disorders can improve rheumatological outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norton", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "9", "8" ] ] }, "page" : "268-278", "title" : "Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1093/rheumatology/kes356", "PMID" : "23236191", "abstract" : "OBJECTIVE: To determine whether depression has a temporal association with RA disease activity, treatment persistence and response to therapy.\\n\\nMETHODS: We performed a systematic review encompassing an electronic database search of all published literature since the availability of biologic response modifiers (beginning in 1998) investigating the impact of depression on downstream RA disease progression and treatment.\\n\\nRESULTS: Only seven articles that evaluated temporal relationships between depression and RA outcomes comprising disease activity, treatment persistence and response to therapy, were included in the review. Results from these studies suggest that depression may exacerbate pain and disease activity and decrease the efficacy of pharmacological (i.e. biologic and non-biologic DMARDs) and some non-pharmacological (e.g. cognitive behavioural therapy) RA treatments.\\n\\nCONCLUSION: Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-2", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1785-1794", "title" : "The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: A systematic review", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2,3]", "plainTextFormattedCitation" : "[2,3]", "previouslyFormattedCitation" : "[2,3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2,3]. Depression is rarely measured in rheumatological research ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2007.084848", "ISSN" : "1468-2060", "PMID" : "18375533", "abstract" : "OBJECTIVES: Patient-reported outcomes (PROs) have been increasingly recognised as important in rheumatoid arthritis (RA). The objective of this study was to assess the frequency of use of different PROs in recently published RA articles and to compare the tools used through a systemic literature review.\n\nMETHODS: (1) DATA SOURCE: In PUBMED MEDLINE database, articles reporting any type of clinical study for adult patients with RA, published between February 2005 and February 2007, and reporting any type of PRO. Articles were excluded if they did not concern adult RA or if they did not report any PROs. (2) DATA EXTRACTION: demographic characteristics of patients, study design, treatment assessed and all PROs. (3) DATA ANALYSIS: descriptive.\n\nRESULTS: Of 109 reports, 50 (45%) were randomised controlled trials and 59 were other types of studies. A total of 63 questionnaires or tools for PROs were used, corresponding to 14 domains of health. Frequently reported domains (and most frequent tools) were: function, 83% (most frequent tool, health assessment questionnaire, HAQ); patient global assessment, 61% (most frequent tool, visual analogue scale, VAS); pain, 56% (VAS); and morning stiffness 27%. Domains such as fatigue, coping or sleep disturbance were infrequently reported.\n\nCONCLUSIONS: PROs are reported with great heterogeneity in recently published trials in RA. Some domains that appear important from the patient's perspective are infrequently reported. Further work is needed in this field.", "author" : [ { "dropping-particle" : "", "family" : "Kalyoncu", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dougados", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daur\u00e8s", "given" : "J-P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gossec", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2", "1" ] ] }, "page" : "183-90", "title" : "Reporting of patient-reported outcomes in recent trials in rheumatoid arthritis: a systematic literature review.", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[12]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4]; assessment of mental health is usually limited to assessment of mental health domains on health-related quality-of-life (HRQoL) questionnaires such as the Medical Outcomes Survey 36-item Short-Form (SF36) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ware", "given" : "John E Jr.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherbourne", "given" : "Cathy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Care", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "473-483", "title" : "The MOS 36-Item Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5]", "plainTextFormattedCitation" : "[5]", "previouslyFormattedCitation" : "[13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5] or the EQ5D ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/36.5.551", "ISSN" : "1462-0324", "author" : [ { "dropping-particle" : "", "family" : "Hurst", "given" : "N. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kind", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruta", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stubbings", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5", "1" ] ] }, "page" : "551-559", "title" : "Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D)", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[6]", "plainTextFormattedCitation" : "[6]", "previouslyFormattedCitation" : "[14]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[6]. The development of biologic treatments for RA have revolutionised the management of RA; in comparison to conventional DMARDs, biologics contribute to increased likelihood of disease remission, and significantly improve physical function ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket266", "ISSN" : "1462-0324", "author" : [ { "dropping-particle" : "", "family" : "Callhoff", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weiss", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zink", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Listing", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2013", "12", "1" ] ] }, "page" : "2127-2135", "title" : "Impact of biologic therapy on functional status in patients with rheumatoid arthritis--a meta-analysis", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2013-204577", "ISSN" : "0003-4967", "author" : [ { "dropping-particle" : "", "family" : "Nam", "given" : "Jackie L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ramiro", "given" : "Sofia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gaujoux-Viala", "given" : "Cecile", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Takase", "given" : "Kaoru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leon-Garcia", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Emery", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gossec", "given" : "Laure", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Landewe", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Smolen", "given" : "Josef S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buch", "given" : "Maya H", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the Rheumatic Diseases", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2014", "3" ] ] }, "page" : "516-528", "title" : "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", "type" : "article-journal", "volume" : "73" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[7,8]", "plainTextFormattedCitation" : "[7,8]", "previouslyFormattedCitation" : "[4,5]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[7,8]. There is, however, a dearth of research examining the relationship between depression and long-term disease outcomes in RA ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kes356", "PMID" : "23236191", "abstract" : "OBJECTIVE: To determine whether depression has a temporal association with RA disease activity, treatment persistence and response to therapy.\\n\\nMETHODS: We performed a systematic review encompassing an electronic database search of all published literature since the availability of biologic response modifiers (beginning in 1998) investigating the impact of depression on downstream RA disease progression and treatment.\\n\\nRESULTS: Only seven articles that evaluated temporal relationships between depression and RA outcomes comprising disease activity, treatment persistence and response to therapy, were included in the review. Results from these studies suggest that depression may exacerbate pain and disease activity and decrease the efficacy of pharmacological (i.e. biologic and non-biologic DMARDs) and some non-pharmacological (e.g. cognitive behavioural therapy) RA treatments.\\n\\nCONCLUSION: Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1785-1794", "title" : "The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: A systematic review", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[3]", "plainTextFormattedCitation" : "[3]", "previouslyFormattedCitation" : "[3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[3]. The impact of comorbid depression on biologic treatment response has previously been investigated in a United States register; the authors reported an association between depressive symptomatology and likelihood of remission at 6-month follow-up, purported to be driven by an association between depression and subjective experiences of disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.clinthera.2016.06.007", "ISSN" : "01492918", "abstract" : "PURPOSE Depressive symptoms are common in rheumatoid arthritis (RA) and may affect disease activity and treatment outcomes. The objective of this study was to determine if prevalent depressive symptoms modify biologic treatment response through their effect on RA disease activity. METHODS RA patients with depressive symptoms, initiating biologic treatment, were identified from a US RA registry sample. Patients with depression were compared with control subjects (ie, those patients with no reports of depressive symptoms at, or before, initiating therapy) in terms of clinical disease activity index (CDAI) remission and low disease activity (LDA), and the changes in the component measures that comprise this scale at 6 and 12 months of follow-up. Inverse probability weighting was used to account for differences in baseline disease severity, concomitant treatment characteristics, and other possible confounders. Logistic and linear regression models estimated differences in response rates and changes in component disease activity measures. FINDINGS Depressive symptoms were associated with a decreased likelihood of CDAI remission at 6 months (odds ratio, 0.43 [95% CI, 0.19\u20130.96]) but not at 12 months (odds ratio, 0.83 [95% CI, 0.43\u20131.60]), and there was no effect on CDAI LDA. Adjusted core component measurement changes showed smaller decreases in global assessment ratings in patients with depressive symptoms; these associations were not statistically significant. IMPLICATIONS Poorer treatment outcomes among RA patients with depressive symptoms may be a result of higher baseline disease severity. Adjusted estimates indicated symptoms of depression only affected remission at 6 months\u2019 follow-up through patient and physician global assessments. Thus, any impact of depressive symptoms during biologic treatment might not be due to a definitive impact on joint swelling and tenderness.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Therapeutics", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1759-1772.e3", "title" : "A prospective evaluation of the effects of prevalent depressive symptoms on disease activity in rheumatoid arthritis patients treated with biologic response modifiers", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[9]", "plainTextFormattedCitation" : "[9]", "previouslyFormattedCitation" : "[6]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[9]. Their assessment was limited to a one-item depression comorbidity tick-box, which may result in high false-positive rates due to poor specificity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "09601643", "PMID" : "17263931", "abstract" : "Background: Guidance from the National Institute for Health and Clinical Excellence recommends one or two questions as a possible screening method for depression. Ultra-short (one-, two-, three- or four-item) tests have appeal due to their simple administration but their accuracy has not been established. Aim: To determine whether ultra-short screening instruments accurately detect depression in primary care. Design of study: Pooled analysis and meta analysis. Method: A literature search revealed 75 possible studies and from these, 22 STARD-compliant studies (Standards for Reporting of Diagnostic Accuracy) involving ultra-short tests were entered in the analysis. Results: Meta-analysis revealed a performance accuracy better than chance (P<0.001). More usefully for clinicians, pooled analysis of single-question tests revealed an overall sensitivity of 32.0% and specificity of 97.0% (positive predictive value [PPV] was 55.6% and negative predictive value [NPV] was 92.3%). For two- and three-item tests, overall sensitivity on pooled analysis was 73.7% and specificity was 74.7% with a PPV of only 38.3% but a pooled NPV of 93.0%. The Youden index for single-item and multiple item tests was 0.289 and 0.47 respectively, suggesting superiority of multiple item tests. Re-analysis examining only 'either or' strategies improved the 'rule in' ability of two- and three-question tests (sensitivity 79.4% and NPV 94.7%) but at the expense of being able to rule out a possible diagnosis if the result was negative. Conclusion: A one-question test identifies only three out of every 10 patients with depression in primary care, thus unacceptable if relied on alone. Ultra-short two- or three-question tests perform better, identifying eight out of 10 cases. This is at the expense of a high false-positive rate (only four out of 10 cases with a positive score are actually depressed). Ultra-short tests appear to be, at best, a method for ruling out a diagnosis and should only be used when there are sufficient resources for second-stage assessment of those who screen positive. \u00a9 British Journal of General Practice 2007.", "author" : [ { "dropping-particle" : "", "family" : "Mitchell", "given" : "Alex J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coyne", "given" : "James C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "British Journal of General Practice", "id" : "ITEM-1", "issue" : "535", "issued" : { "date-parts" : [ [ "2007", "2" ] ] }, "page" : "144-151", "title" : "Do ultra-short screening instruments accurately detect depression in primary care?. A pooled analysis and meta- analysis of 22 studies", "type" : "article-journal", "volume" : "57" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[10]", "plainTextFormattedCitation" : "[10]", "previouslyFormattedCitation" : "[7]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[10]. Analysis of the Norwegian Disease-Modifying Anti-Rheumatic Drug (NOR-DMARD) database identified an association between depressive symptoms at the start of treatment with biological or synthetic DMARDs, and reduced risk of remission and higher pain and global assessment at 3- and 6- month follow-up ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/annrheumdis-2017-211284", "abstract" : "AbstrACt Objective to investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (rA) and psoriatic arthritis (psA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up. Methods We included 1326 patients with rA and 728 patients with psA from the prospective observational nor-DMArD study starting first-time tumour necrosis factor inhibitors or methotrexate. the predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models. results Baseline depression/anxiety according to euroQoL-5D-3L, short Form-36 (sF-36) Mental Health subscale \u226456 and sF-36 Mental Component summary \u226438 negatively predicted 28-joint Disease Activity score <2.6, simplified Disease Activity index \u22643.3, Clinical Disease Activity index \u22642.8, ACr/eULAr Boolean and Disease Activity index for psoriatic Arthritis \u22644 remission after 3 and 6 months treatment in rA (p\u22640.008) and partly in psA (p from 0.001 to 0.73). Baseline depression/anxiety was associated with increased patient's and evaluator's global assessment, tender joint count and joint pain in rA at follow-up, but not with swollen joint count and acute phase reactants. Conclusion Depression and anxiety may reduce likelihood of joint remission based on composite scores in rA and psA and should be taken into account in individual patients when making a shared decision on a treatment target.", "author" : [ { "dropping-particle" : "", "family" : "Michelsen", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristianslund", "given" : "Klami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sexton", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammer", "given" : "Hilde Berner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fagerli", "given" : "Karen Minde", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lie", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wier\u00f8d", "given" : "Ada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalstad", "given" : "Syn\u00f8ve", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f8devand", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kr\u00f8ll", "given" : "Frode", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haugeberg", "given" : "Glenn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kvien", "given" : "Tore K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ann Rheum Dis", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-5", "title" : "Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR- DMARD study", "type" : "article-journal", "volume" : "0" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[11]", "plainTextFormattedCitation" : "[11]", "previouslyFormattedCitation" : "[8]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[11]. To date, there is stronger evidence for a relationship between depressive symptoms and subjective experiences of disease such a patient global assessment (PGA) and pain ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kev306", "ISSN" : "1462-0332", "PMID" : "26350486", "abstract" : "OBJECTIVE: The aim of this analysis is to examine the longitudinal impact of symptoms of depression/anxiety on treatment response, long-term disease activity and physical disability in RA. METHODS: Secondary analysis of clinical trial data was performed. Data were collected at baseline and at 6-monthly intervals for 2 years. The EuroQoL (EQ-5D(TM)) indicated depression/anxiety symptom severity. Our primary outcomes of interest were (i) DAS-28 and (ii) physical disability measured via the HAQ. Secondary outcomes were: tender and swollen joint counts, patient global assessment, ESR and odds of reaching clinical remission. Multilevel models were used to assess the impact of baseline and persistent depression/anxiety on outcomes over 2 years. RESULTS: Data from 379 patients were included. After adjusting for covariates, baseline depression/anxiety symptoms were associated with increased DAS-28 outcomes and increased tender joint counts. Persistent depression/anxiety symptoms were associated with increased DAS-28 scores, HAQ scores, tender joint counts and patient global assessment of disease activity, and reduced odds of reaching clinical remission. Patients with symptoms of depression/anxiety at baseline also showed a 50% reduction in prednisolone treatment effect, in comparison with patients with no symptoms of depression/anxiety at baseline. CONCLUSION: Baseline and persistent symptoms of depression/anxiety are associated with poorer health outcomes over time, as well as reduced treatment response. Mental health should be routinely measured both in clinical practice and in research, and managed alongside rheumatological disease to optimize health outcomes. Further research is required to examine whether treatment of mental disorders can improve rheumatological outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norton", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "9", "8" ] ] }, "page" : "268-278", "title" : "Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2017-211284", "abstract" : "AbstrACt Objective to investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (rA) and psoriatic arthritis (psA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up. Methods We included 1326 patients with rA and 728 patients with psA from the prospective observational nor-DMArD study starting first-time tumour necrosis factor inhibitors or methotrexate. the predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models. results Baseline depression/anxiety according to euroQoL-5D-3L, short Form-36 (sF-36) Mental Health subscale \u226456 and sF-36 Mental Component summary \u226438 negatively predicted 28-joint Disease Activity score <2.6, simplified Disease Activity index \u22643.3, Clinical Disease Activity index \u22642.8, ACr/eULAr Boolean and Disease Activity index for psoriatic Arthritis \u22644 remission after 3 and 6 months treatment in rA (p\u22640.008) and partly in psA (p from 0.001 to 0.73). Baseline depression/anxiety was associated with increased patient's and evaluator's global assessment, tender joint count and joint pain in rA at follow-up, but not with swollen joint count and acute phase reactants. Conclusion Depression and anxiety may reduce likelihood of joint remission based on composite scores in rA and psA and should be taken into account in individual patients when making a shared decision on a treatment target.", "author" : [ { "dropping-particle" : "", "family" : "Michelsen", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristianslund", "given" : "Klami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sexton", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammer", "given" : "Hilde Berner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fagerli", "given" : "Karen Minde", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lie", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wier\u00f8d", "given" : "Ada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalstad", "given" : "Syn\u00f8ve", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f8devand", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kr\u00f8ll", "given" : "Frode", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haugeberg", "given" : "Glenn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kvien", "given" : "Tore K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ann Rheum Dis", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-5", "title" : "Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR- DMARD study", "type" : "article-journal", "volume" : "0" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1136/annrheumdis-2011-200338", "ISSN" : "1468-2060", "PMID" : "21917827", "abstract" : "BACKGROUND: Cross-sectional associations suggest a mutual impact of disease activity and psychological distress in rheumatoid arthritis (RA), but a prospective association has not been established.\n\nOBJECTIVE: To examine concurrent and prospective associations between psychological distress and disease activity.\n\nMETHODS: Patients with RA (N=545, disease duration \u22641 year, age 18-83 years, 69% female, 64% rheumatoid factor (RF) positive) were monitored for 5 years. The Thompson joint score and erythrocyte sedimentation rate were assessed every 6 months. Depressed mood and anxiety were measured every 12 months. Multilevel regression analysis was used. RF positivity, age and female sex were included as covariates.\n\nRESULTS: Concurrent levels of psychological distress and disease activity were positively associated (p\u22640.04). Prospectively, depressed mood was associated with disease activity levels 6 months later (p\u22640.04). The Thompson joint score was associated with psychological distress levels 6 months later (p\u22640.03) and also with an increase in depressed mood over the subsequent 6 months (p=0.02). No other significant prospective associations were found (p\u22650.07).\n\nCONCLUSIONS: Psychological distress and disease activity are positively associated when measured at the same time as well as when measured 6 months apart. While some support was found for the idea that a higher level of disease activity is a risk factor for an increase in psychological distress, the results do not support the notion that psychological distress is a risk factor for future exacerbation of disease activity.", "author" : [ { "dropping-particle" : "", "family" : "Overman", "given" : "C\u00e9cile L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bossema", "given" : "Ercolie R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Middendorp", "given" : "Henri\u00ebt", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wijngaards-de Meij", "given" : "Leoniek", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verstappen", "given" : "Suzanne M M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bulder", "given" : "Marcia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Johannes W G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bijlsma", "given" : "Johannes W J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Geenen", "given" : "Rinie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-3", "issue" : "2", "issued" : { "date-parts" : [ [ "2012", "2", "1" ] ] }, "page" : "192-7", "title" : "The prospective association between psychological distress and disease activity in rheumatoid arthritis: a multilevel regression analysis.", "type" : "article-journal", "volume" : "71" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1002/acr.22515", "ISSN" : "2151464X", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Care & Research", "id" : "ITEM-4", "issue" : "6", "issued" : { "date-parts" : [ [ "2015", "5" ] ] }, "page" : "765-775", "title" : "Temporal effect of depressive symptoms on the longitudinal evolution of rheumatoid arthritis disease activity", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2,11\u201313]", "plainTextFormattedCitation" : "[2,11\u201313]", "previouslyFormattedCitation" : "[2,8\u201310]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2,11–13], contributing to a growing focus on re-defining remission in RA ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/acr.23284", "ISSN" : "2151464X", "PMID" : "28544615", "abstract" : "OBJECTIVES In current management paradigms of Rheumatoid Arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role. METHODS This was a cross-sectional, single centre study including consecutive ambulatory RA patients. Data collection comprised swollen (SJC28) and tender joint counts (TJC28), C-Reactive protein (CRP), PGA, pain, fatigue, function, anxiety, depression, happiness, personality traits, and comorbidities. Remission was categorised using ACR/EULAR Boolean-based criteria: remission, near-remission (only PGA>1) and non-remission. A binary definition without PGA (3v-Remission) was also studied. Univariable and multivariable analyses were used to identify explanatory variables of PGA in each remission state. RESULTS 309 patients were included (remission: 9.4%; near-remission: 37.2%; non-remission: 53.4%). Patients in near-remission were indistinguishable from remission regarding disease activity, but described a disease impact similar to those in non-remission. In multivariable analyses, PGA in near-remission was explained (R(2)adjusted =.50) by fatigue, pain, anxiety and function. Fatigue and pain had no relationship with disease activity measures. CONCLUSION In RA, a consensually acceptable level of disease activity (SJC28, TJC28, and CRP\u22641) does not equate to low disease impact: a large proportion of these patients are considered in non-remission solely due to PGA. PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immunosuppressive therapy. This suggests that clinical practice should be guided by two separate remission targets: inflammation (3v-Remission) and disease impact. This article is protected by copyright. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Ferreira", "given" : "Ricardo J. O.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duarte", "given" : "C\u00e1tia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ndosi", "given" : "Mwidimi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wit", "given" : "Maarten", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gossec", "given" : "Laure", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Silva", "given" : "J. A. P.", "non-dropping-particle" : "da", "parse-names" : false, "suffix" : "" } ], "container-title" : "Arthritis Care & Research", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2017", "5", "23" ] ] }, "title" : "Suppressing inflammation in rheumatoid arthritis: Does patient global assessment blur the target? A practice-based call for a paradigm change", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[14]", "plainTextFormattedCitation" : "[14]", "previouslyFormattedCitation" : "[11]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[14].The present study seeks to examine the longitudinal association between depressive symptoms and treatment response in a UK national register of RA patients starting their first biologic. In comparison to previous research ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.clinthera.2016.06.007", "ISSN" : "01492918", "abstract" : "PURPOSE Depressive symptoms are common in rheumatoid arthritis (RA) and may affect disease activity and treatment outcomes. The objective of this study was to determine if prevalent depressive symptoms modify biologic treatment response through their effect on RA disease activity. METHODS RA patients with depressive symptoms, initiating biologic treatment, were identified from a US RA registry sample. Patients with depression were compared with control subjects (ie, those patients with no reports of depressive symptoms at, or before, initiating therapy) in terms of clinical disease activity index (CDAI) remission and low disease activity (LDA), and the changes in the component measures that comprise this scale at 6 and 12 months of follow-up. Inverse probability weighting was used to account for differences in baseline disease severity, concomitant treatment characteristics, and other possible confounders. Logistic and linear regression models estimated differences in response rates and changes in component disease activity measures. FINDINGS Depressive symptoms were associated with a decreased likelihood of CDAI remission at 6 months (odds ratio, 0.43 [95% CI, 0.19\u20130.96]) but not at 12 months (odds ratio, 0.83 [95% CI, 0.43\u20131.60]), and there was no effect on CDAI LDA. Adjusted core component measurement changes showed smaller decreases in global assessment ratings in patients with depressive symptoms; these associations were not statistically significant. IMPLICATIONS Poorer treatment outcomes among RA patients with depressive symptoms may be a result of higher baseline disease severity. Adjusted estimates indicated symptoms of depression only affected remission at 6 months\u2019 follow-up through patient and physician global assessments. Thus, any impact of depressive symptoms during biologic treatment might not be due to a definitive impact on joint swelling and tenderness.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Therapeutics", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1759-1772.e3", "title" : "A prospective evaluation of the effects of prevalent depressive symptoms on disease activity in rheumatoid arthritis patients treated with biologic response modifiers", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[9]", "plainTextFormattedCitation" : "[9]", "previouslyFormattedCitation" : "[6]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[9], this study utilises three measures of depression symptoms: history of depression comorbidity tick-box, the mental health domain of the SF36, and the depression/anxiety item of the EQ5D, providing an opportunity to investigate the differential relationships between depression symptoms and treatment outcomes based on mental health assessment strategy. The aims are: 1) to examine the relationship between baseline depression symptoms and biologic treatment response over 1-year follow-up; 2) to evaluate the relationship between baseline depression symptoms and disease activity over 1-year.MethodsParticipantsThis study presents an analysis of the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA; ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keq209", "ISSN" : "1462-0332", "PMID" : "20671021", "abstract" : "OBJECTIVES Anti-TNF therapy has significantly improved outcomes for patients with severe RA. In the UK, changing financial restrictions and increasing experience with their use may have resulted in changes to the way physicians use anti-TNF therapies. The aim of this analysis was to examine changes in disease characteristics and response rates among patients starting anti-TNF therapy for RA over an 8-year period. METHODS A total of 11\u2009216 RA patients registered between 2001 and 2008 with the British Society for Rheumatology Biologics Register were included and stratified according to year of first anti-TNF prescription. Baseline characteristics and treatment response were compared year on year using logistic and linear regression models. RESULTS Mean RA disease activity and severity of new anti-TNF-treated patients decreased between 2001 and 2008. The mean disease duration remained high (11 years in 2008) although the proportion of patients having disease duration<5 years increased significantly (2001: 9%; 2008: 29%; P<0.001). The majority of patients had failed three DMARDs on average before the first anti-TNF prescription. There was an increase in both the proportion of EULAR good responders at 1 year (2001: 18%; 2008: 30%; P<0.001) and in the number of patients achieving remission (2001: 8%; 2008: 17%; P<0.001). Drug survival remained relatively stable over the study years. CONCLUSIONS There is a significant trend towards earlier use of anti-TNF therapies in patients with less severe disease, although the mean disease duration at first treatment remains high. This has correlated with improvements in outcome. These results support the earlier use of anti-TNF therapies in RA.", "author" : [ { "dropping-particle" : "", "family" : "Hyrich", "given" : "Kimme L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Watson", "given" : "Kath D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lunt", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Symmons", "given" : "Deborah P M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "British Society for Rheumatology Biologics Register (BSRBR)", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2011", "1" ] ] }, "page" : "117-23", "title" : "Changes in disease characteristics and response rates among patients in the United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid arthritis between 2001 and 2008.", "type" : "article-journal", "volume" : "50" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[15]", "plainTextFormattedCitation" : "[15]", "previouslyFormattedCitation" : "[15]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[15]). The BSRBR-RA is a national prospective register of RA patients starting a new biologic, and contains data from 18,421 patients enrolled since its inception in 2001. To be eligible for inclusion in the BSRBR-RA, patients must meet UK guidelines for commencing a biologics: sustained active RA (defined as scoring >5.1 on the DAS28 at two timepoints a month apart); and failure to respond to ≥ conventional Disease modifying Anti-Rheumatic Drugs (DMARDs) including methotrexate over a ≥6 month timeframe ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keq006b", "author" : [ { "dropping-particle" : "", "family" : "Deighton", "given" : "Chris", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hyrich", "given" : "Kimme", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ding", "given" : "Tina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ledingham", "given" : "Jo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lunt", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luqmani", "given" : "Raashid", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kiely", "given" : "Patrick", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bukhari", "given" : "Marwan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abernethy", "given" : "Rikki", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ostor", "given" : "Andrew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bosworth", "given" : "Ailsa", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gadsby", "given" : "Kate", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mckenna", "given" : "Frank", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Finney", "given" : "Diana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dixey", "given" : "Josh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1197-9", "title" : "BSR and BHPR rheumatoid arthritis guidelines on eligibility criteria for the first biological therapy", "type" : "article-journal", "volume" : "49" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[16]", "plainTextFormattedCitation" : "[16]", "previouslyFormattedCitation" : "[16]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[16]. A range of clinical, demographic and psychological assessments are taken at baseline, 6-monthly intervals for the first 3-years of follow-up, and yearly thereafter. We limited our analysis to first biologic exposure only. AssessmentsDepression SymptomsThree measures of depressive symptoms are available in the BSRBR-RA database: upon enrolment, all patients are asked if they have ever had or received treatment for depression, which was used as an indicator of history of depression. The SF36 ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ware", "given" : "John E Jr.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherbourne", "given" : "Cathy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Care", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "473-483", "title" : "The MOS 36-Item Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5]", "plainTextFormattedCitation" : "[5]", "previouslyFormattedCitation" : "[13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5] was used as an assessment of HRQoL between 2001-2008, in the first 11,937 enrolled patients. A threshold of ≤40 on the normed mental health (nMH) subscale of the SF36 has been shown to have a 92.6% sensitivity and 73.2% specificity for identifying depression in patients with RA ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12891-016-1083-y", "ISSN" : "1471-2474", "abstract" : "This study aimed to assess the accuracy of the Short-Form Health Survey (SF-36) mental health subscale (MH) and mental component summary (MCS) scores in identifying the presence of probable major depressive or anxiety disorder in patients with rheumatoid arthritis. SF-36 data were collected in 100 hospital outpatients with rheumatoid arthritis. MH and MCS scores were compared against depression and anxiety data collected using validated measures as part of routine clinical practice. Sensitivity and specificity of the SF-36 were established using receiver operating characteristic (ROC) curve analysis, and area under the curve (AUC) compared the performance of the SF-36 components with the 9-item Patient Health Questionnaire (PHQ9) for depression and the 7-item Generalised Anxiety Disorder (GAD7) questionnaire for anxiety. The MH with a threshold of \u226452 had sensitivity and specificity of 81.0 and 71.4 % respectively to detect anxiety, correctly classifying 73.5 % of patients with probable anxiety disorder. A threshold of \u226456 had sensitivity and specificity of 92.6 and 73.2 % respectively to detect depression, correctly classifying 78.6 % of patients, and the same threshold could also be used to detect either depression or anxiety with a sensitivity of 87.9 %, specificity of 76.9 % and accuracy of 80.6 %. The MCS with a threshold of \u226435 had sensitivity and specificity of 85.7 and 81.9 % respectively to detect anxiety, correctly classifying 82.8 % of patients with probable anxiety disorder. A threshold of \u226440 had sensitivity and specificity of 92.3 and 70.2 % respectively to detect depression, correctly classifying 76.3 % of patients. A threshold of \u226438 could be used to detect either depression or anxiety with a sensitivity of 87.5 %, specificity of 80.3 % and accuracy of 82.8 %. This analysis may increase the utility of a widely-used questionnaire. Overall, optimal use of the SF-36 for screening for mental disorder may be through using the MCS with a threshold of \u226438 to identify the presence of either depression or anxiety.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norton", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Musculoskeletal Disorders", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016", "12", "23" ] ] }, "page" : "224", "title" : "Usefulness of the SF-36 Health Survey in screening for depressive and anxiety disorders in rheumatoid arthritis", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[17]", "plainTextFormattedCitation" : "[17]", "previouslyFormattedCitation" : "[17]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[17]. Responses to the SF36 were categorised using this threshold, to represent patients with low HRQoL. The EQ5D ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/36.5.551", "ISSN" : "1462-0324", "author" : [ { "dropping-particle" : "", "family" : "Hurst", "given" : "N. P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kind", "given" : "P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ruta", "given" : "D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hunter", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Stubbings", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "5", "issued" : { "date-parts" : [ [ "1997", "5", "1" ] ] }, "page" : "551-559", "title" : "Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D)", "type" : "article-journal", "volume" : "36" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[6]", "plainTextFormattedCitation" : "[6]", "previouslyFormattedCitation" : "[14]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[6] was introduced to the BSRBR-RA in 2005 and became the only HRQoL assessment from 2010 onwards. The EQ5D has one item specific to mental health, allowing patients to identify whether they are feeling “not depressed/anxious”, “moderately depressed/anxious”, or “extremely depressed/anxious” today. Evidence suggests that one-item mood screeners have 84% sensitivity and 65% specificity ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "National Institute for Health and Care Excellence", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2009" ] ] }, "language" : "eng", "publisher" : "NICE", "publisher-place" : "", "title" : "Depression in adults with a chronic physical health problem: recognition and management (clinical guideline CG91)", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[18]", "plainTextFormattedCitation" : "[18]", "previouslyFormattedCitation" : "[18]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[18], and this item has been previously used to predict longitudinal DAS28 and HAQ outcomes, and prednisolone treatment response in RA patients ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kev306", "ISSN" : "1462-0332", "PMID" : "26350486", "abstract" : "OBJECTIVE: The aim of this analysis is to examine the longitudinal impact of symptoms of depression/anxiety on treatment response, long-term disease activity and physical disability in RA. METHODS: Secondary analysis of clinical trial data was performed. Data were collected at baseline and at 6-monthly intervals for 2 years. The EuroQoL (EQ-5D(TM)) indicated depression/anxiety symptom severity. Our primary outcomes of interest were (i) DAS-28 and (ii) physical disability measured via the HAQ. Secondary outcomes were: tender and swollen joint counts, patient global assessment, ESR and odds of reaching clinical remission. Multilevel models were used to assess the impact of baseline and persistent depression/anxiety on outcomes over 2 years. RESULTS: Data from 379 patients were included. After adjusting for covariates, baseline depression/anxiety symptoms were associated with increased DAS-28 outcomes and increased tender joint counts. Persistent depression/anxiety symptoms were associated with increased DAS-28 scores, HAQ scores, tender joint counts and patient global assessment of disease activity, and reduced odds of reaching clinical remission. Patients with symptoms of depression/anxiety at baseline also showed a 50% reduction in prednisolone treatment effect, in comparison with patients with no symptoms of depression/anxiety at baseline. CONCLUSION: Baseline and persistent symptoms of depression/anxiety are associated with poorer health outcomes over time, as well as reduced treatment response. Mental health should be routinely measured both in clinical practice and in research, and managed alongside rheumatological disease to optimize health outcomes. Further research is required to examine whether treatment of mental disorders can improve rheumatological outcomes.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norton", "given" : "Sam", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scott", "given" : "David L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016", "9", "8" ] ] }, "page" : "268-278", "title" : "Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial.", "type" : "article-journal", "volume" : "55" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2]", "plainTextFormattedCitation" : "[2]", "previouslyFormattedCitation" : "[2]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2]. Treatment ResponseThe primary outcome of interest was 1-year treatment response, measured by the European League Against Rheumatism (EULAR) guidelines ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Fransen", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Riel", "given" : "P L C M", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and Experimental Rheumatology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "S93-9", "title" : "The Disease Activity Score and the EULAR response criteria", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[19]", "plainTextFormattedCitation" : "[19]", "previouslyFormattedCitation" : "[19]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[19]. Based on their 1-year EULAR response, patients were categorised into those demonstrating a good treatment response and those with a suboptimal treatment response (none/moderate response).Disease activitySecondary outcomes were disease activity (measured via the DAS28), and its composite parts: tender joint count (TJC); swollen joint count (SJC); patient global assessment (PGA); and erythrocyte sedimentation rate (ESR); all measured at 1-year follow-up. TJC and SJC underwent square root transformation and ESR data were log transformed for analysis.Statistical AnalysisAlthough data were available for three years of follow-up, only data until the first year of follow-up were included. This ensured a focus on first biologic exposure, eliminating bias introduced by patients switching biologics due to a lack of treatment response. All analyses were conducted on Stata v14. Clinical and demographic characteristics of patients having a good treatment response by 1-year were compared with those with no/moderate treatment response using means and standard deviations, with statistically significant imbalance determined using t-tests for continuous variables and Chi- squared tests for categorical data.Aim 1: The impact of baseline depressive symptoms on 1-year biologic treatment responseLogistic regression models were performed in 2 stages: unadjusted (model 1), then adjusted for age, gender, disease duration, baseline DAS28, baseline HAQ, and number of comorbidities (model 2). Logistic regression estimates the odds of a binary outcome (i.e. having a good treatment response), based on several predictor variables (i.e. baseline depression). In all models, baseline depressive symptomatology was entered as the predictor variable: history of depression (yes/no); SF36 nMH subscale (≤40/>40); EQ5D (no/moderate/extreme)). Treatment response at 1-year (none/moderate vs. good) was the outcome variable in primary analyses. Odds ratios (OR), p-values and 95% confidence intervals estimated whether the presence of depressive symptoms at biologic initiation was associated with increased odds of having a good treatment response at 1-year. Multiple imputation was used to address baseline missing data for DAS28, disease duration and HAQ. Aim 2: Relationship between baseline depressive symptoms and time-course disease activity over 1-yearThe relationships between baseline depression and 1-year DAS28, TJC, SJC, PGA and ESR were examined using multilevel longitudinal models, pooling data across the timepoints (baseline, 6-months and 1-year) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1037/a0012765", "author" : [ { "dropping-particle" : "", "family" : "Kwok O", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Underhill", "given" : "AT", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berry", "given" : "JW", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Luo", "given" : "W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elliott", "given" : "TR", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yoon", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rehabilitation Psychology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "370-386", "title" : "Analyzing longitudinal data with multilevel models: An example with individuals living with lower extremity intra-articular fractures", "type" : "article-journal", "volume" : "53" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[20]", "plainTextFormattedCitation" : "[20]", "previouslyFormattedCitation" : "[20]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[20]. Multilevel modelling handles hierarchically nested data, accounting for missing data, and both between- and within- participant variation over time, and multiple imputation was used to address baseline missing data for DAS28, disease duration and HAQ.Output from multilevel models includes unstandardized maximum likelihood estimates (B coefficients), which estimate the magnitude and direction of change in an outcome variable according to a reference group (no depressive symptoms at baseline). In addition to depressive symptoms as a predictor variable and DAS28 (and its composite parts) as outcome variables, multilevel models included time as a continuous variable coded as 0 at baseline, 1 at 6-months and 2 at 12-months, and the interaction between time and baseline depressive symptoms, to examine whether change over time is different between people with and without symptoms of depression at baseline. A random intercept and random time slope allowed for variation in the baseline level of the outcome and the rate of change in the outcome between individuals. The random effects were allowed to correlate, which means that some control for the baseline level of the outcome is included in the model even though it is not included as a covariate – e.g. a positive correlation would allow for increasing variability in the outcome variable over time ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Twisk", "given" : "Jos WR", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "publisher" : "Cambridge University Press", "title" : "Applied longitudinal data analysis for epidemiology: a practical guide", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[21]", "plainTextFormattedCitation" : "[21]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[21]. Multilevel models were created in two stages: 1) including only baseline depression symptoms, time and an interaction between time and depression symptoms, plus random effects; and 2) additionally adjusting for age, gender, disease duration, comorbidities, and baseline physical activity (measured via the Health Assessment Questionnaire (HAQ) ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Bruce", "given" : "Bonnie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fries", "given" : "James F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical and Experimental Rheumatology", "id" : "ITEM-1", "issue" : "39", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "14-18", "title" : "The Health Assessment Questionnaire (HAQ)", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[22]", "plainTextFormattedCitation" : "[22]", "previouslyFormattedCitation" : "[21]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[22]). Covariates were selected based on theoretical relevance. RESULTSMissing dataFigure 1 shows the data available for analysis for the primary outcome (treatment response) and secondary outcome (disease activity), in relation to the different methods of depressive symptom measurement. Missing response status/disease activity outcome data at 1-year was associated with increased BMI, and lower baseline DAS28, TJC, SJC, ESR and HAQ, shown in supplementary table t1. Baseline depression symptoms, according to all three measurements available, was not associated with missing outcome data. Participant characteristicsData from 18,421 patients enrolled in the BSRBR-RA by December 2015 were included in this analysis (figure 1). Table 1 displays baseline demographic, clinical and psychological variables for all patients. The mean age was 56.4 years, 76.4% were female, with a mean disease duration of 12.6 years and mean DAS28 of 6.4. By 6-months, 3,638 patients had achieved a good treatment response. At 1-year, a total of 5,271 (34.3%) of patients having reached a DAS28 of ≤3.2 and an improvement in DAS28 from baseline of >1.2.At 1-year follow-up, 17.9% of patients were identified as switching biologic. Biologic switching was significantly higher in patients reporting a history of depression, and depressive symptoms according to the SF36 and EQ5D at baseline (supplementary table t3). Figure SEQ Figure \* ARABIC 1. Summary of the number of patients available for each outcome analysis. ^percentages calculated from the total sample.Table SEQ Table \* ARABIC 1. BSRBR-RA cohort baseline characteristics for total group, and according to baseline depressive symptoms. History of depressionSF36 nMH depression symptomsEQ5D depression symptomsTotal Sample (N=18,421)No (N=14,426; 73.7%)Yes (N=3,669; 20.3%)p-valueNo (N=5,388 (45.1%))Yes (N=6,549, 54.9%)p-valueNone (N=2,761 (44.6%))Moderate (N=2,975 (48.1%))Extreme (N=453 (N=7.3%))p-valueAge, M (SD)56.4 (12.4)56.6 (12.6)55.2 (11.4)<0.000155.9 (12.1)56.1 (12.3)0.0757.6 (12.9)57.1 (12.4)54.8 (11.5)<0.0001Female Gender, N (%)14,065 (76.4)10,799 (74.9)2,999 (81.7)<0.00014,056 (75.3)5,057 (77.2)0.012,094 (75.8)2,299 (77.3)354 (78.2)0.329BMI, M(SD)27.3 (6.6)27.1 (6.5)28.1 (6.8)<0.000126.8 (6.4)27.0 (6.2)<0.000127.7 (7.1)28.2 (7.3)29.6 (7.5)<0.0001Disease Duration, years, M(SD)12.6 (9.7)12.7 (9.8)12.3 (9.6)0.00113.1 (9.5)12.9 (9.7)0.00712.1 (10.0)11.8 (10.0)9.8 (9.6)<0.0001Smoking, N(%)Current3,733 (20.3)2,762 920.2)922 (27.3)<0.00011,053 (19.7)1,546 (23.8)<0.0001420 (17.9)593 (23.4)118 (30.2)<0.0001Ex-smoker6,584 (35.7)5,176 (37.9)1,312 (38.9)2,119 (39.6)2,415 (37.1)897 (38.2)979 (38.6)135 (34.5)Never smoked6,990 (38.0)5,736 (42.0)1,141 (33.8)2,176 (40.7)2,546 (39.1)1,031 (43.9)967 (38.1)138 (35.3)Comorbidity, N(%)*9,988 (55.5)7,565 (53.3)2,281 (63.5)<0.00012,747 (52.0)3,561 (55.4)<0.0001N comorbidities, M(SD)*0.9 (1.0)0.8 (1.0)1.1 (1.2)<0.00010.8 (1.0)0.9 (1.0)<0.00010.9 (1.1)1.0 (1.1)1.1 (1.3)<0.0001Treatment Type, N(%)Etanercept5,356 (29.1)4,232 (29.3)1,039 (28.3)<0.00011,797 (33.5)2,275 (34.7)0.001298 (10.8)259 (8.7)39 (8.6)<0.0001Infliximab4,249 (23.1)3,348 (23.2)853 (23.3)1,587 (29.5)2,062 (31.5)72 (2.6)122 (4.1)19 (4.2)Adalimumab5,024 (27.3)4,044 (28.0)904 (24.6)1,992 (37.0)2,196 (33.5)840 (30.4)993 (33.4)162 (35.8)Rituximab1,650 (9.0)1,208 (8.4)393 (10.7)12 (0.22)16 (0.24)654 (23.7)813 (27.3)100 (22.1)Tocilizumab1,008 (5.5)709 (4.9)267 (7.3)--411 (14.9)378 (12.7)68 (15.0)Certolizumab1,115 (6.1)870 (6.0)210 (5.7)--478 (17.3)404 (13.6)65 (14.4)Infliximab Biosimilar19 (0.1)15 (0.1)3 (0.1)--8 (0.3)6 (0.2)0 (0.0)Baseline disease statusDAS28, M(SD)6.4 (1.1)6.4 (1.1)6.4 (1.1)<0.00016.5 (1.0)6.6 (1.0)<0.00015.9 (1.2)6.1 (1.1)6.3 (1.0)<0.0001TJC, M(SD)15.2 (7.5)15.0 (7.5)15.9 (7.5)<0.000115.2 (7.3)15.9 (7.4)<0.000113.6 (7.5)15.0 (7.5)16.2 (7.3)<0.0001SJC, M(SD)10.5 (6.1)10.6 (6.1)10.0 (6.1)0.14111.2 (6.1)11.5 (6.2)<0.00018.7 (5.9)9.0 (5.7)9.1 (5.9)<0.0001PGA, M(SD)72.0 (20.0)71.6 (20.1)73.6 (19.6)<0.000170.5 (20.0)74.2 (19.3)<0.000168.5 (21.0)72.5 (18.8)79.1 (18.5)<0.0001ESR, M(SD)43.2 (28.4)47.0 (29.1)35.9 (25.1)<0.000145.2 (12.1)46.5 (28.6)<0.000136.0 (26.9)37.8 (27.6)38.8 (29.0)<0.0001HAQ, M(SD)1.9 (0.6)1.9 (0.6)2.1 (0.6)<0.00011.9 (0.6)2.1 (0.6)<0.00011.5 (0.7)1.9 (0.6)2.2 (0.5)<0.0001RF+, N(%)11,275 (64.3)8,985 (64.1)2,113 (62.1)0.0023,465 (64.4)4,267 (65.2)0.3241,484 (61.5)1,669 (62.5)255 (63.9)0.58Good 1-year treatment response, N(%)*5,271 (34.3)4,293 (35.5)917 (30.0)<0.0001?1,665 (34.7)1,759 (30.1)<0.0001?997 (44.7)856 (34.9)97 (26.4)<0.0001*data available for 15,386 participants. Table SEQ Table \* ARABIC 2. Association between baseline depression and treatment response at 12-months.History of depression SF36 (nMH≤40)EQ5D ??OR95%CIpOR95%CIpOR95%CIpUnadjustedDepression symptoms (vs. none)0.750.66, 0.85<0.00010.790.69, 0.920.002---Moderate depression symptoms (vs. none)------0.760.63, 0.910.003Extreme depression symptoms (vs. none)------0.510.38, 0.69<0.0001Adjusted*Depression symptoms (vs. no depression)0.800.69, 0.920.0020.900.77, 1.180.177---Moderate depression symptoms (vs. none)------0.850.69, 1.04 0.105?Extreme depression symptoms (vs. none)---?---?0.620.45, 0.870.005* adjusted for age, gender, disease duration, baseline DAS28, number of comorbidities, baseline HAQ. SF36 Medical Outcomes Survey 36-item Short Form. nMH normed Mental Health subscale. OR odds ratio. CI confidence interval. N Number of participants included in analysis. History of depressionIn comparison to patients without a history of depression, logistic regression indicated that patients reporting a history of depression have reduced odds (OR=0.80, 95%CI: 0.69-0.92) of having a good treatment response by 1-year follow-up after adjusting for covariates (table 2). Using multilevel longitudinal models, patients reporting a history of depression reported significantly lower levels of baseline DAS28 (B=-0.07, 95%CI:-0.12, -0.02) but a significantly lower rate of improvement in DAS28 over time in comparison to patients without a history of depression (table 3). Those without a history of depression reported a total improvement in DAS28 of -0.4 at 1-year, whereas. patients with a history of depression reported a decrease in DAS28 score of -0.36 between baseline and 1-year follow-up (table 3). This significant interaction effect is displayed graphically in figure 2. Supplementary tables t3-t6 show the results of the multilevel longitudinal analyses examining the relationship between history of depression status and TJC, SJC, PGA and ESR outcomes respectively. Patients without a history of depression show significantly reduced improvement in all components over time in comparison to patients with a history of depression. SF36 nMH subscaleIn comparison to patients scoring ≤40 on the SF36 nMH subscale, logistic regression analysis revealed that those scoring >40, had no significant difference in the odds of having a good treatment response at one-year follow-up (table 2). According to multilevel longitudinal analysis, there were no differences in baseline DAS28 levels between those scoring ≤40 and >40 on the nMH subscale, although patients scoring ≤40 reported a significantly reduced rate of improvement in DAS28 over time in comparison to those scoring >40. Whereas patients scoring >40 on the nMH reduce in DAS28 scores by -0.42 at 1-year, patients scoring ≤40 show an overall improvement in DAS28 of -0.40 by one-year follow-up (table 3). This significant interaction effect is shown graphically in figure 2.Supplementary tables t3-t6 show the results of the multilevel analyses examining the relationship between nMH status and TJC, SJC, PGA and ESR outcomes respectively. Depressive symptomatology according to the SF36 nMH subscale was not associated with change in PGA or ESR scores over time, however patients scoring ≤40 showed reduced improvements in TJC and SJC outcomes in comparison to patients scoring >40.EQ5DLogistic regression analysis adjusting for covariates, reveals no significant difference in odds of having a good treatment response between patients reporting no depression symptoms and those reported moderate symptoms (OR=0.85, 95%CI: 0.69-1.04). In comparison to patients reporting no depression symptoms, those reporting extreme depression symptoms had a significantly reduced odds of a good treatment response at 1-year follow-up (OR=0.62, 95%CI: 0.45-0.87) (table 2). Results of longitudinal multilevel analyses reveal no significant difference between depression symptom groups and baseline levels of DAS28, however in comparison to patients with no depression symptoms at baseline, those with moderate and extreme symptoms show significantly reduced rate of improvement over time. In comparison to patients with no symptoms of depression according to the EQ5D, who improve by -0.38 at 1-year follow-up, patients with some symptoms and extreme symptoms report reductions in DAS28 of -0.34 and -0.32 respectively at one-year follow-up (table 3). The significant interaction between depression symptoms and follow-up timepoint is displayed graphically in figure 2. Supplementary tables t3-t6 show the results of the multilevel analyses examining the relationship between EQ5D status and TJC, SJC, PGA and ESR outcomes respectively. In comparison to patients with no symptoms of depression at baseline, those with moderate symptoms show significantly reduced improvements in TJC, SJC, PGA and ESR over time. In comparison to patients with no symptoms of depression at baseline, those with extreme symptoms show significantly reduced improvements in TJC, SJC and ESR over time.Table SEQ Table \* ARABIC 3.Association between baseline depression, and DAS28 outcomes over 12-month follow-up.History of depression?SF36 (nMH ≤40)?EQ5DB95%CIp?B95%CIp?B95%CIpUnadjustedDepression symptoms (vs. none)0.03-0.02, 0.080.2940.140.09, 0.19<0.0001---Moderate depression symptoms (vs. none)------0.250.18, 0.32<0.0001Extreme depression symptoms (vs. none)------0.500.36, 0.64<0.0001Follow-up number-0.20-0.21, -0.20<0.0001-0.21-0.21, -0.20<0.0001-0.19-0.20, -0.18<0.0001Depression*follow-up0.020.02, 0.03<0.00010.010.00, 0.010.003---Moderate depression (vs. none)------0.020.01, 0.03<0.0001Extreme depression (vs. none)---?---?0.030.01, 0.05<0.0001Adjusted^Depression symptoms (vs. none)-0.07-0.12, -0.020.0110.03-0.02, 0.080.276---Moderate depression symptoms (vs. none)------0.04-0.04, 0.110.364Extreme depression symptoms (vs. none)------0.11-0.04, 0.260.144Follow-up number-0.20-0.21, -0.20<0.0001-0.21-0.21, -0.20<0.0001-0.19-0.20, -0.19<0.0001Depression symptoms*follow-up0.020.02, 0.03<0.00010.010.00, 0.010.002Moderate depression symptoms (vs. none)------0.020.01, 0.03<0.0001Extreme depression symptoms (vs. none)---?---?0.030.01, 0.050.001^model adjusted for age, gender, disease duration, comorbidities and baseline HAQ. B unstandardized coefficient.SF36 Medical Outcomes Survey 36-item Short Form. nMH normed Mental Health subscale. Figure SEQ Figure \* ARABIC 2. Graphical representation of fully-adjusted interactions between baseline depression symptoms and time on DAS28 outcomes over 12-month follow-up.DISCUSSIONThis study found symptoms of depression at baseline to be associated with reduced long-term odds of reaching clinical remission in patients receiving their first biologic drug. This supports previous evidence from US and Norwegian demonstrating reduced likelihood of reaching remission in patients with symptoms of depression at treatment initiation ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.clinthera.2016.06.007", "ISSN" : "01492918", "abstract" : "PURPOSE Depressive symptoms are common in rheumatoid arthritis (RA) and may affect disease activity and treatment outcomes. The objective of this study was to determine if prevalent depressive symptoms modify biologic treatment response through their effect on RA disease activity. METHODS RA patients with depressive symptoms, initiating biologic treatment, were identified from a US RA registry sample. Patients with depression were compared with control subjects (ie, those patients with no reports of depressive symptoms at, or before, initiating therapy) in terms of clinical disease activity index (CDAI) remission and low disease activity (LDA), and the changes in the component measures that comprise this scale at 6 and 12 months of follow-up. Inverse probability weighting was used to account for differences in baseline disease severity, concomitant treatment characteristics, and other possible confounders. Logistic and linear regression models estimated differences in response rates and changes in component disease activity measures. FINDINGS Depressive symptoms were associated with a decreased likelihood of CDAI remission at 6 months (odds ratio, 0.43 [95% CI, 0.19\u20130.96]) but not at 12 months (odds ratio, 0.83 [95% CI, 0.43\u20131.60]), and there was no effect on CDAI LDA. Adjusted core component measurement changes showed smaller decreases in global assessment ratings in patients with depressive symptoms; these associations were not statistically significant. IMPLICATIONS Poorer treatment outcomes among RA patients with depressive symptoms may be a result of higher baseline disease severity. Adjusted estimates indicated symptoms of depression only affected remission at 6 months\u2019 follow-up through patient and physician global assessments. Thus, any impact of depressive symptoms during biologic treatment might not be due to a definitive impact on joint swelling and tenderness.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Therapeutics", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2016" ] ] }, "page" : "1759-1772.e3", "title" : "A prospective evaluation of the effects of prevalent depressive symptoms on disease activity in rheumatoid arthritis patients treated with biologic response modifiers", "type" : "article-journal", "volume" : "38" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2017-211284", "abstract" : "AbstrACt Objective to investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (rA) and psoriatic arthritis (psA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up. Methods We included 1326 patients with rA and 728 patients with psA from the prospective observational nor-DMArD study starting first-time tumour necrosis factor inhibitors or methotrexate. the predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models. results Baseline depression/anxiety according to euroQoL-5D-3L, short Form-36 (sF-36) Mental Health subscale \u226456 and sF-36 Mental Component summary \u226438 negatively predicted 28-joint Disease Activity score <2.6, simplified Disease Activity index \u22643.3, Clinical Disease Activity index \u22642.8, ACr/eULAr Boolean and Disease Activity index for psoriatic Arthritis \u22644 remission after 3 and 6 months treatment in rA (p\u22640.008) and partly in psA (p from 0.001 to 0.73). Baseline depression/anxiety was associated with increased patient's and evaluator's global assessment, tender joint count and joint pain in rA at follow-up, but not with swollen joint count and acute phase reactants. Conclusion Depression and anxiety may reduce likelihood of joint remission based on composite scores in rA and psA and should be taken into account in individual patients when making a shared decision on a treatment target.", "author" : [ { "dropping-particle" : "", "family" : "Michelsen", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristianslund", "given" : "Klami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sexton", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammer", "given" : "Hilde Berner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fagerli", "given" : "Karen Minde", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lie", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wier\u00f8d", "given" : "Ada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalstad", "given" : "Syn\u00f8ve", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f8devand", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kr\u00f8ll", "given" : "Frode", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haugeberg", "given" : "Glenn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kvien", "given" : "Tore K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ann Rheum Dis", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-5", "title" : "Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR- DMARD study", "type" : "article-journal", "volume" : "0" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[9,11]", "plainTextFormattedCitation" : "[9,11]", "previouslyFormattedCitation" : "[6,8]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[9,11]. We also identified prospective associations between baseline depression symptom status and disease activity, with depression symptoms contributing to increased DAS28 over the 12-month follow-up, and impacting change in DAS28 in response to treatment. Examination of the DAS28 components identified associations between depression and both subjective and objective aspects of disease activity; effect sizes did not differ between subjective and objective outcomes, contradicting previous research findings emphasising the relationship between depressive symptoms and subjective experiences of disease ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kes356", "PMID" : "23236191", "abstract" : "OBJECTIVE: To determine whether depression has a temporal association with RA disease activity, treatment persistence and response to therapy.\\n\\nMETHODS: We performed a systematic review encompassing an electronic database search of all published literature since the availability of biologic response modifiers (beginning in 1998) investigating the impact of depression on downstream RA disease progression and treatment.\\n\\nRESULTS: Only seven articles that evaluated temporal relationships between depression and RA outcomes comprising disease activity, treatment persistence and response to therapy, were included in the review. Results from these studies suggest that depression may exacerbate pain and disease activity and decrease the efficacy of pharmacological (i.e. biologic and non-biologic DMARDs) and some non-pharmacological (e.g. cognitive behavioural therapy) RA treatments.\\n\\nCONCLUSION: Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1785-1794", "title" : "The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: A systematic review", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1136/annrheumdis-2017-211284", "abstract" : "AbstrACt Objective to investigate the predictive value of baseline depression/anxiety on the likelihood of achieving joint remission in rheumatoid arthritis (rA) and psoriatic arthritis (psA) as well as the associations between baseline depression/anxiety and the components of the remission criteria at follow-up. Methods We included 1326 patients with rA and 728 patients with psA from the prospective observational nor-DMArD study starting first-time tumour necrosis factor inhibitors or methotrexate. the predictive value of depression/anxiety on remission was explored in prespecified logistic regression models and the associations between baseline depression/anxiety and the components of the remission criteria in prespecified multiple linear regression models. results Baseline depression/anxiety according to euroQoL-5D-3L, short Form-36 (sF-36) Mental Health subscale \u226456 and sF-36 Mental Component summary \u226438 negatively predicted 28-joint Disease Activity score <2.6, simplified Disease Activity index \u22643.3, Clinical Disease Activity index \u22642.8, ACr/eULAr Boolean and Disease Activity index for psoriatic Arthritis \u22644 remission after 3 and 6 months treatment in rA (p\u22640.008) and partly in psA (p from 0.001 to 0.73). Baseline depression/anxiety was associated with increased patient's and evaluator's global assessment, tender joint count and joint pain in rA at follow-up, but not with swollen joint count and acute phase reactants. Conclusion Depression and anxiety may reduce likelihood of joint remission based on composite scores in rA and psA and should be taken into account in individual patients when making a shared decision on a treatment target.", "author" : [ { "dropping-particle" : "", "family" : "Michelsen", "given" : "Brigitte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kristianslund", "given" : "Klami", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sexton", "given" : "Joseph", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hammer", "given" : "Hilde Berner", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fagerli", "given" : "Karen Minde", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lie", "given" : "Elisabeth", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wier\u00f8d", "given" : "Ada", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalstad", "given" : "Syn\u00f8ve", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "R\u00f8devand", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kr\u00f8ll", "given" : "Frode", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haugeberg", "given" : "Glenn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kvien", "given" : "Tore K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Ann Rheum Dis", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "1-5", "title" : "Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR- DMARD study", "type" : "article-journal", "volume" : "0" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1186/s12891-016-1011-1", "ISSN" : "14712474", "abstract" : "\u00a9 2016 Matcham et al.Background: This study aimed to investigate the impact of depression and anxiety scores on disease activity at 1-year follow-up in people with Rheumatoid Arthritis (RA). Methods: The Hospital Anxiety Depression Scale (HADS) was used to measure depression and anxiety in a cross-section of RA patients. The primary outcome of interest was disease activity (DAS28), measured one-year after baseline assessment. Secondary outcomes were: tender joint count, swollen joint count, erythrocyte sedimentation rate and patient global assessment, also measured one-year after baseline assessment. We also examined the impact of baseline depression and anxiety on odds of reaching clinical remission at 1-year follow-up. Results: In total, 56 RA patients were eligible for inclusion in this analysis. Before adjusting for key demographic and disease variables, increased baseline depression and anxiety were associated with increased disease activity at one-year follow-up, although this was not sustained after adjusting for baseline disease activity. There was a strong association between depression and anxiety and the subjective components of the DAS28 at 12-month follow-up: tender joint count and patient global assessment. After adjusting for age, gender, disease duration and baseline tender joint count and patient global assessment respectively, higher levels of depression and anxiety at baseline were associated with increased tender joint count and patient global assessment scores at 1-year follow-up. Conclusions: Symptoms of depression and anxiety have implications for disease activity, as measured via the DAS28, primarily due to their influence on tender joints and patient global assessment. These findings have implications for treatment decision-making as inflated DAS28 despite well controlled inflammatory disease markers may indicate significant psychological morbidity and related non-inflammatory pain, rather than true disease activity.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ali", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Irving", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chalder", "given" : "T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Musculoskeletal Disorders", "id" : "ITEM-3", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Are depression and anxiety associated with disease activity in rheumatoid arthritis? A prospective study", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[3,11,23]", "plainTextFormattedCitation" : "[3,11,23]", "previouslyFormattedCitation" : "[3,8,22]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[3,11,23]. There are several explanations for this novel finding. Firstly, depression is known to impact health behaviours such as medication adherence ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "ioi90679 [pii]", "ISBN" : "0003-9926", "ISSN" : "0003-9926", "PMID" : "10904452", "abstract" : "BACKGROUND: Depression and anxiety are common in medical patients and are associated with diminished health status and increased health care utilization. This article presents a quantitative review and synthesis of studies correlating medical patients' treatment noncompliance with their anxiety and depression. METHODS: Research on patient adherence catalogued on MEDLINE and PsychLit from January 1, 1968, through March 31, 1998, was examined, and studies were included in this review if they measured patient compliance and depression or anxiety (with n>10); involved a medical regimen recommended by a nonpsychiatrist physician to a patient not being treated for anxiety, depression, or a psychiatric illness; and measured the relationship between patient compliance and patient anxiety and/or depression (or provided data to calculate it). RESULTS: Twelve articles about depression and 13 about anxiety met the inclusion criteria. The associations between anxiety and noncompliance were variable, and their averages were small and nonsignificant. The relationship between depression and noncompliance, however, was substantial and significant, with an odds ratio of 3.03 (95% confidence interval, 1.96-4.89). CONCLUSIONS: Compared with nondepressed patients, the odds are 3 times greater that depressed patients will be noncompliant with medical treatment recommendations. Recommendations for future research include attention to causal inferences and exploration of mechanisms to explain the effects. Evidence of strong covariation of depression and medical noncompliance suggests the importance of recognizing depression as a risk factor for poor outcomes among patients who might not be adhering to medical advice.", "author" : [ { "dropping-particle" : "", "family" : "DiMatteo", "given" : "M R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lepper", "given" : "H S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Croghan", "given" : "T W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Archives of internal medicine", "id" : "ITEM-1", "issue" : "14", "issued" : { "date-parts" : [ [ "2000" ] ] }, "page" : "2101-2107", "title" : "Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence.", "type" : "article-journal", "volume" : "160" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[24]", "plainTextFormattedCitation" : "[24]", "previouslyFormattedCitation" : "[23]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[24], and non-adherence to biologics has been shown to reduce DAS28 treatment response ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/keu358", "ISSN" : "1462-0332", "author" : [ { "dropping-particle" : "", "family" : "Bluett", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Catharine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thurston", "given" : "Layla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plant", "given" : "Darren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hyrich", "given" : "Kimme L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morgan", "given" : "Ann W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wilson", "given" : "Anthony G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Isaacs", "given" : "John D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cordingley", "given" : "Lis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barton", "given" : "Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2015", "3", "1" ] ] }, "page" : "494-499", "publisher" : "Oxford University Press", "title" : "Impact of inadequate adherence on response to subcutaneously administered anti-tumour necrosis factor drugs: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort", "type" : "article-journal", "volume" : "54" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[25]", "plainTextFormattedCitation" : "[25]", "previouslyFormattedCitation" : "[24]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[25]. Whilst adherence data is not collected for all contributors to the BSRBR-RA databset and not available for inclusion in this paper, the role of adherence as a mechanism for this relationship is a valuable area for future research. Secondly, there may be a biological explanation for these findings. Systemic inflammation and elevated cytokines typically associated with RA disease manifestation and disease severity are also identified in people with depressive disorder ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jad.2011.08.003", "ISSN" : "1573-2517", "PMID" : "21872339", "abstract" : "BACKGROUND: Many studies have explored the association between soluble interleukin-2 receptor (sIL-2R), cytokines and major depressive disorder (MDD). However, the results of these studies were not consistent. The aim of our study is to compare the levels of sIL-2R and cytokines in the blood between MDD patients and controls by a meta-analysis and to identify moderators accounting for potential heterogeneity in the levels of sIL-2R and cytokines in MDD patients versus controls by meta-regression analyses.\n\nMETHODS: A comprehensive literature search was performed to identify studies comparing the levels of sIL-2R and cytokines between MDD patients and controls. We pooled the effect sizes for standardized mean differences (SMD) of the levels of sIL-2R and cytokines. We also performed meta-regression and sensitivity analyses to investigate the roles of age, gender, sample type, ethnic origin and selected studies' quality in explaining potential heterogeneity and differences in results respectively.\n\nRESULTS: Twenty-nine studies were selected for this analysis. The levels of sIL-2R, TNF-\u03b1 and IL-6 in MDD patients were significantly higher than those of healthy controls (SMD=0.555, p<0.001, SMD=0.567, p=0.010; SMD=0.680, p<0.001). Mean age of all subjects was a significant moderator to explain the high heterogeneity of IL-6. Sensitivity analysis found that European but not non-European subjects have higher levels difference of sIL-2R, TNF-\u03b1 and IL-1\u03b2 between MDD patients and controls.\n\nLIMITATION: The severity of MDD was not considered.\n\nCONCLUSION: The blood levels of sIL-2R, TNF-\u03b1 and IL-6 were significantly higher in MDD patients than controls. Age, samples source and ethnic origins may play a potential role in heterogeneity.", "author" : [ { "dropping-particle" : "", "family" : "Liu", "given" : "Yang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ho", "given" : "Roger Chun-Man", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mak", "given" : "Anselm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of affective disorders", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "8" ] ] }, "page" : "230-9", "title" : "Interleukin (IL)-6, tumour necrosis factor alpha (TNF-\u03b1) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression.", "type" : "article-journal", "volume" : "139" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.biopsych.2009.09.033", "ISSN" : "1873-2402", "PMID" : "20015486", "abstract" : "BACKGROUND: Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls.\n\nMETHODS: We performed a meta-analysis of studies measuring cytokine concentration in patients with major depression, with a database search of the English literature (to August 2009) and a manual search of references.\n\nRESULTS: Twenty-four studies involving unstimulated measurements of cytokines in patients meeting DSM criteria for major depression were included in the meta-analysis; 13 for tumor necrosis factor (TNF)-alpha, 9 for interleukin (IL)-1beta, 16 for IL-6, 5 for IL-4, 5 for IL-2, 4 for IL-8, 6 for IL-10, and 4 for interferon (IFN)-gamma. There were significantly higher concentrations of TNF-alpha (p < .00001), weighted mean difference (WMD) (95% confidence interval) 3.97 pg/mL (2.24 to 5.71), in depressed subjects compared with control subjects (438 depressed/350 nondepressed). Also, IL-6 concentrations were significantly higher (p < .00001) in depressed subjects compared with control subjects (492 depressed/400 nondepressed) with an overall WMD of 1.78 pg/mL (1.23 to 2.33). There were no significant differences among depressed and nondepressed subjects for the other cytokines studied.\n\nCONCLUSIONS: This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects. While both positive and negative results have been reported in individual studies, this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS.", "author" : [ { "dropping-particle" : "", "family" : "Dowlati", "given" : "Yekta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Herrmann", "given" : "Nathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Swardfager", "given" : "Walter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Helena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sham", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reim", "given" : "Elyse K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lanct\u00f4t", "given" : "Krista L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biological psychiatry", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2010", "3", "1" ] ] }, "page" : "446-57", "title" : "A meta-analysis of cytokines in major depression.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1016/j.semarthrit.2013.08.004", "abstract" : "a b s t r a c t Objective: The disease burden in rheumatoid arthritis (RA) extends beyond the joint. This article evaluates the physical and psychosocial extra-articular burden of treated RA and relationships among diverse disease manifestations. Methods: MEDLINE searches identified papers published in English from January 2003 to December 2012 that evaluated systemic complications and psychosocial aspects associated with RA. Preference was given to studies with randomized cohorts and large (4 100) sample sizes. Of 378 articles identified in the initial search, 118 were selected for inclusion. Results: RA is associated with multiple comorbidities and psychosocial impairments, including cardio-vascular disease, osteoporosis, interstitial lung disease, infection, malignancies, fatigue, depression, cognitive dysfunction, reduced work performance, work disability, and decreased health-related quality of life. The etiology of the extra-articular burden may reflect the systemic inflammation and immune system alteration associated with RA, metabolic imbalances and side effects related to treatment, or the influence of comorbidities. Strategies that may help to reduce the extra-articular disease burden include personalized medicine and the potential introduction of treatments with new mechanisms of action. Conclusion: Despite improvements in treating joint disease, the extra-articular burden in RA remains substantial, encompassing multiple comorbidities and psychosocial impairments.", "author" : [ { "dropping-particle" : "", "family" : "Cutolo", "given" : "Maurizio", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kitas", "given" : "George D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "LCM van Riel", "given" : "Piet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Seminars in Arthritis and Rheumatism", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "479-488", "title" : "Burden of disease in treated rheumatoid arthritis patients: Going beyond the joint", "type" : "article-journal", "volume" : "43" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[26\u201328]", "plainTextFormattedCitation" : "[26\u201328]", "previouslyFormattedCitation" : "[25\u201327]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[26–28]. Finally, the large sample size available for this analysis may have provided sufficient statistical power to identify small effect sizes typically unobservable in smaller datasets. We identified differential effects of symptoms of depression symptoms on rheumatological outcomes, based on the depression assessment method. Whereas a history of depression and EQ5D categories were largely predictive of all assessed outcomes, either showing a main effect or modifying change over time, the SF36 was not associated with ESR or PGA. This may be due to these assessments representing different elements of mental health. Ticking a depression comorbidity tick box may indicate a lifetime history of depression, or exposure to mental health treatment, however it provides no timeframe or qualifications for endorsement ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1155/2013/563246", "ISSN" : "2090-1429", "abstract" : "Background. Everything known about the roles, relationships, and repercussions of comorbidity in cardiovascular disease is shaped by how comorbidity is currently measured. Objectives. To critically examine how comorbidity is measured in randomized controlled trials or clinical trials and prospective observational studies in acute myocardial infarction (AMI), heart failure (HF), or stroke. Design. Systematic review of studies of hospitalized adults from MEDLINE CINAHL, PsychINFO, and ISI Web of Science Social Science databases. At least two reviewers screened and extracted all data. Results. From 1432 reviewed abstracts, 26 studies were included (AMI , HF , stroke ). Five studies used an instrument to measure comorbidity while the remaining used the presence or absence of an unsubstantiated list of individual diseases. Comorbidity data were obtained from 1&#x2013;4 different sources with 35&#x25; of studies not reporting the source. A year-by-year analysis showed no changes in measurement. Conclusions. The measurement of comorbidity remains limited to a list of conditions without stated rationale or standards increasing the likelihood that the true impact is underestimated.", "author" : [ { "dropping-particle" : "", "family" : "Buck", "given" : "Harleah G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akbar", "given" : "Jabar A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Sarah Jingying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bettger", "given" : "Janet A. Prvu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buck", "given" : "Harleah G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akbar", "given" : "Jabar A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhang", "given" : "Sarah Jingying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bettger", "given" : "Janet A. Prvu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Nursing Research and Practice", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1-11", "title" : "Measuring comorbidity in cardiovascular research: A systematic review", "type" : "article-journal", "volume" : "2013" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[29]", "plainTextFormattedCitation" : "[29]", "previouslyFormattedCitation" : "[28]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[29]. As the history of depression assessment may include people who have previously received treatment for depression, they may not be experiencing current symptomatology. This measure should be viewed as lifetime depression prevalence, rather than presence of current symptomatology.The SF36, alternatively, contains multiple items covering a range of psychological symptoms, including happiness, nervousness, calmness, tiredness and participation in social activities ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Ware", "given" : "John E Jr.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sherbourne", "given" : "Cathy D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical Care", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1992" ] ] }, "page" : "473-483", "title" : "The MOS 36-Item Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5]", "plainTextFormattedCitation" : "[5]", "previouslyFormattedCitation" : "[13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5] and is framed to detect a change from normality within the last month. It may represent a more nuanced perspective of mental health, including positive and negative affect, as well as psychosomatic and behavioural symptoms often associated with chronic illness. We used thresholds based on a validation study ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1186/s12891-016-1083-y", "ISSN" : "14712474", "abstract" : "\u00a9 2016 Matcham et al.Background: This study aimed to assess the accuracy of the Short-Form Health Survey (SF-36) mental health subscale (MH) and mental component summary (MCS) scores in identifying the presence of probable major depressive or anxiety disorder in patients with rheumatoid arthritis. Methods: SF-36 data were collected in 100 hospital outpatients with rheumatoid arthritis. MH and MCS scores were compared against depression and anxiety data collected using validated measures as part of routine clinical practice. Sensitivity and specificity of the SF-36 were established using receiver operating characteristic (ROC) curve analysis, and area under the curve (AUC) compared the performance of the SF-36 components with the 9-item Patient Health Questionnaire (PHQ9) for depression and the 7-item Generalised Anxiety Disorder (GAD7) questionnaire for anxiety. Results: The MH with a threshold of \u226452 had sensitivity and specificity of 81.0 and 71.4 % respectively to detect anxiety, correctly classifying 73.5 % of patients with probable anxiety disorder. A threshold of \u226456 had sensitivity and specificity of 92.6 and 73.2 % respectively to detect depression, correctly classifying 78.6 % of patients, and the same threshold could also be used to detect either depression or anxiety with a sensitivity of 87.9 %, specificity of 76.9 % and accuracy of 80.6 %. The MCS with a threshold of \u226435 had sensitivity and specificity of 85.7 and 81.9 % respectively to detect anxiety, correctly classifying 82.8 % of patients with probable anxiety disorder. A threshold of \u226440 had sensitivity and specificity of 92.3 and 70.2 % respectively to detect depression, correctly classifying 76.3 % of patients. A threshold of \u226438 could be used to detect either depression or anxiety with a sensitivity of 87.5 %, specificity of 80.3 % and accuracy of 82.8 %. Conclusion: This analysis may increase the utility of a widely-used questionnaire. Overall, optimal use of the SF-36 for screening for mental disorder may be through using the MCS with a threshold of \u226438 to identify the presence of either depression or anxiety.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Norton", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMC Musculoskeletal Disorders", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "Usefulness of the SF-36 Health Survey in screening for depressive and anxiety disorders in rheumatoid arthritis", "type" : "article-journal", "volume" : "17" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[30]", "plainTextFormattedCitation" : "[30]", "previouslyFormattedCitation" : "[29]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[30], but the high prevalence of “depression” measured on the SF-36 suggests a lack of specificity which may have reduced effect sizes due to measurement error ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1191/0269216302pm507oa", "abstract" : "Objective: To identify all literature regarding depression in patients with advanced cancer and among mixed hospice populations, and to summarise the prevalence of depression according to different definitions. Methods: A systematic review was performed using extensive electronic and hand searches. All studies with quantitative data on prevalence of depression were included and categorised according to their definition of depression. Results: We identified 46 eligible studies giving information on the prevalence of depression, and a further four which gave information on case finding. The most widely used assessment of depression was the Hospital Anxiety and Depression Scale (HADS), which gave a median prevalence of definite depression' (i.e., a score on the depression subscale of 10 of 29%, (interquartile range, IQR, 19.50 34.25%). Studies that used psychiatric interviews indicated a prevalence of major depressive disorder ranging from 5% to 26%, with a median of 15%. Studies were generally small (median sample size 88.5, IQR 50 108), had high numbers of nonresponders, and rarely gave confidence intervals for estimates of prevalence. Conclusions: Depression is a common problem in palliative care settings. The quality of much of the available research is poor, based on small samples of patients with very high nonparticipation rates. The clinical importance of depression is described in subsequent papers.", "author" : [ { "dropping-particle" : "", "family" : "Hotopf", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chidgey", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Addington-Hall", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ly", "given" : "K Lan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Palliative Medicine", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2002", "3", "1" ] ] }, "page" : "81-97", "title" : "Depression in advanced disease: a systematic review Part 1. Prevalence and case finding", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[31]", "plainTextFormattedCitation" : "[31]", "previouslyFormattedCitation" : "[30]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[31]. The EQ5D assesses current depressive symptomatology, and although by no means a diagnostic test for depression, representing moderate sensitivity and specificity, the low proportion of patients reporting “extreme depression/anxiety” is lower than typical prevalence estimates of depression in RA ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/ket169", "ISSN" : "1462-0332", "PMID" : "24003249", "abstract" : "OBJECTIVE: There is substantial uncertainty regarding the prevalence of depression in RA. We conducted a systematic review aiming to describe the prevalence of depression in RA. METHODS: Web of Science, PsycINFO, CINAHL, Embase, Medline and PubMed were searched for cross-sectional studies reporting a prevalence estimate for depression in adult RA patients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a meta-analysis was performed. RESULTS: A total of 72 studies, including 13,189 patients, were eligible for inclusion in the review. Forty-three methods of defining depression were reported. Meta-analyses revealed the prevalence of major depressive disorder to be 16.8% (95% CI 10%, 24%). According to the PHQ-9, the prevalence of depression was 38.8% (95% CI 34%, 43%), and prevalence levels according to the HADS with thresholds of 8 and 11 were 34.2% (95% CI 25%, 44%) and 14.8% (95% CI 12%, 18%), respectively. The main influence on depression prevalence was the mean age of the sample. CONCLUSION: Depression is highly prevalent in RA and associated with poorer RA outcomes. This suggests that optimal care of RA patients may include the detection and management of depression.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steer", "given" : "Sophia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "12", "issued" : { "date-parts" : [ [ "2013", "12", "1" ] ] }, "page" : "2136-48", "title" : "The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis.", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[1]", "plainTextFormattedCitation" : "[1]", "previouslyFormattedCitation" : "[1]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1].This study has used appropriate longitudinal data analysis methodology to examine the long-term relationship between symptoms of depression and biologic treatment response. There is a shortage of high-quality longitudinal investigation in this field, and the evidence that does exist is limited to studies with highly selected samples, suboptimal depression assessments, inadequate adjustment for confounding variables, and inappropriate analysis methodologies ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/rheumatology/kes356", "PMID" : "23236191", "abstract" : "OBJECTIVE: To determine whether depression has a temporal association with RA disease activity, treatment persistence and response to therapy.\\n\\nMETHODS: We performed a systematic review encompassing an electronic database search of all published literature since the availability of biologic response modifiers (beginning in 1998) investigating the impact of depression on downstream RA disease progression and treatment.\\n\\nRESULTS: Only seven articles that evaluated temporal relationships between depression and RA outcomes comprising disease activity, treatment persistence and response to therapy, were included in the review. Results from these studies suggest that depression may exacerbate pain and disease activity and decrease the efficacy of pharmacological (i.e. biologic and non-biologic DMARDs) and some non-pharmacological (e.g. cognitive behavioural therapy) RA treatments.\\n\\nCONCLUSION: Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.", "author" : [ { "dropping-particle" : "", "family" : "Rathbun", "given" : "Alan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reed", "given" : "George W.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Harrold", "given" : "Leslie R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Rheumatology (Oxford, England)", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1785-1794", "title" : "The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: A systematic review", "type" : "article-journal", "volume" : "52" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[3]", "plainTextFormattedCitation" : "[3]", "previouslyFormattedCitation" : "[3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[3]. The current study uses the largest prospective observational biologics registry in the world to examine the impact of depression symptoms on outcomes in real-world patients undergoing biologic treatment. Our results are therefore externally valid, representing patients prescribed biologics across the UK; a diverse population.There are limitations to consider when interpreting these findings. Although providing several interpretations of depression, none of the measurement tools available for baseline depression are “gold-standard” indicators of the presence of diagnostically ascertained depression. Due to the scarcity with which validated screening tools or diagnostic interviews are utilised to measure depression in RA research ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/ard.2007.084848", "ISSN" : "1468-2060", "PMID" : "18375533", "abstract" : "OBJECTIVES: Patient-reported outcomes (PROs) have been increasingly recognised as important in rheumatoid arthritis (RA). The objective of this study was to assess the frequency of use of different PROs in recently published RA articles and to compare the tools used through a systemic literature review.\n\nMETHODS: (1) DATA SOURCE: In PUBMED MEDLINE database, articles reporting any type of clinical study for adult patients with RA, published between February 2005 and February 2007, and reporting any type of PRO. Articles were excluded if they did not concern adult RA or if they did not report any PROs. (2) DATA EXTRACTION: demographic characteristics of patients, study design, treatment assessed and all PROs. (3) DATA ANALYSIS: descriptive.\n\nRESULTS: Of 109 reports, 50 (45%) were randomised controlled trials and 59 were other types of studies. A total of 63 questionnaires or tools for PROs were used, corresponding to 14 domains of health. Frequently reported domains (and most frequent tools) were: function, 83% (most frequent tool, health assessment questionnaire, HAQ); patient global assessment, 61% (most frequent tool, visual analogue scale, VAS); pain, 56% (VAS); and morning stiffness 27%. Domains such as fatigue, coping or sleep disturbance were infrequently reported.\n\nCONCLUSIONS: PROs are reported with great heterogeneity in recently published trials in RA. Some domains that appear important from the patient's perspective are infrequently reported. Further work is needed in this field.", "author" : [ { "dropping-particle" : "", "family" : "Kalyoncu", "given" : "U", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dougados", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Daur\u00e8s", "given" : "J-P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gossec", "given" : "L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of the rheumatic diseases", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "2", "1" ] ] }, "page" : "183-90", "title" : "Reporting of patient-reported outcomes in recent trials in rheumatoid arthritis: a systematic literature review.", "type" : "article-journal", "volume" : "68" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[12]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4], the opportunity to compare three methods in the current paper is helpful, however given the high prevalence and impact of depression on disease outcomes, symptoms of depression should be routinely measured in rheumatological practice. We did not adjust our models for treatment type, or previous failure with conventional DMARDs. As all patients are receiving biologics and there is no well-established association between different types of biologic or DMARD on our dependent or independent variables, we chose not to include treatment type as a confounder in our models. No data were available on concurrent mental health treatment, and it is likely that some patients may have been receiving therapy or antidepressant treatments which may reduce our observed effects. These results contribute to the growing body of literature highlighting the role depression plays in predicting long-term health outcomes and treatment response in RA. These findings have several implications. Repeated screening and management of mental disorder should be undertaken as part of clinical care. Biologics are expensive ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "The British Society for Rheumatology", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "publisher-place" : "", "title" : "Biologic drugs.", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[32]", "plainTextFormattedCitation" : "[32]", "previouslyFormattedCitation" : "[31]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[32], and poor treatment response can result in switching biologics, which can result in further costs ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.3111/13696998.2013.763812", "ISSN" : "1369-6998", "abstract" : "AbstractBackground and objectives:Tumor necrosis factor-alpha (anti-TNF) blocking agents are effective for the treatment of rheumatoid arthritis (RA), with mean response rates of 60\u201370%. Patients with incomplete response to initial anti-TNF treatment often are switched to other biologic treatments with some success. However, little is known about whether or not switching to anti-TNF or other non-TNF biologic treatments is cost-effective. This study sought to review the economic evidence of sequencing various biologic treatments in RA.Methods:A systematic review was conducted of published and unpublished literature (January 2000 to October 2012) on the cost-effectiveness of sequencing biologic treatments in RA after failure of an initial biologic treatment. It included modeling and other economic studies that assessed cost-effectiveness of one or more sequences of biologics. Studies were excluded that evaluated non-biologic sequencing.Results:This review of the available evidence suggests that there is lim...", "author" : [ { "dropping-particle" : "", "family" : "Sullivan", "given" : "Sean D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Alfonso-Cristancho", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Carlson", "given" : "Josh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mallya", "given" : "Usha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ringold", "given" : "Sarah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Medical Economics", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2013", "3", "18" ] ] }, "page" : "391-396", "title" : "Economic consequences of sequencing biologics in rheumatoid arthritis: a systematic review", "type" : "article-journal", "volume" : "16" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[33]", "plainTextFormattedCitation" : "[33]", "previouslyFormattedCitation" : "[32]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[33]. Depression should therefore be routinely measured in RA clinical trials, and in clinical practice. In conclusion, experiencing symptoms of depression at the start of biologics treatment is associated with reduced treatment response, impacting change over time in disease activity. The management of symptoms of depression in routine care is NICE recommended ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "National Collaborating Centre for Mental Health", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "publisher-place" : "", "title" : "Depression in adults with a chronic physical health problem: treatment and management", "type" : "report" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[34]", "plainTextFormattedCitation" : "[34]", "previouslyFormattedCitation" : "[33]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[34], and depression is treatable within the context of long-term physical health conditions ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.cpr.2014.01.005", "PMID" : "24508685", "abstract" : "Psychological distress, depression and anxiety are common in most physical diseases, and self-help interventions, if effective, might be an important approach to improve outcomes as they are inexpensive to provide to large numbers of patients. The primary aim of this review was to assess randomised controlled trials examining the impact of self-help interventions on symptoms of depression, anxiety and psychological distress in patients with physical illness. Systematic searches of electronic databases resulted in twenty-five eligible studies for meta-analysis (n=4211). The results of the primary meta-analyses revealed a significant improvement in depression symptoms, in favour of the intervention group (SMD=-0.13, 95% CI: -0.25, -0.02, p=0.02, I2=50%). There were no significant differences in symptoms of anxiety (SMD=-0.10, 95% CI: -0.24, 0.05, p=0.20, I2=63%) or psychological distress (SMD=-0.14, 95% CI: -0.40, 0.12, p=0.30, I2=72%) between intervention and control conditions. Several subgroup and sensitivity analyses improved effect sizes, suggesting that optimal mental health outcomes may be obtained in patients without neurological conditions, and with interventions based on a therapeutic model (such as cognitive behavioural therapy), and with stress management components. This review demonstrates that with appropriate design and implementation, self-help interventions may potentially improve symptoms of depression in patients with physical conditions. \u00a9 2014 Elsevier Ltd.", "author" : [ { "dropping-particle" : "", "family" : "Matcham", "given" : "Faith", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rayner", "given" : "L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hutton", "given" : "J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Monk", "given" : "A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Steel", "given" : "C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Clinical Psychology Review", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "141-157", "title" : "Self-help interventions for symptoms of depression, anxiety and psychological distress in patients with physical illnesses: A systematic review and meta-analysis", "type" : "article", "volume" : "34" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1097/RHU.0000000000000489", "ISSN" : "1076-1608", "PMID" : "28221313", "abstract" : "BACKGROUND Psychiatric comorbidities, such as depression and anxiety, are very common in persons with rheumatoid arthritis (RA) and can lead to adverse outcomes. By appropriately treating these comorbidities, disease-specific outcomes and quality of life may be improved. OBJECTIVE The aim of this study was to systematically review the literature from controlled trials of treatments for depression and anxiety in persons with RA. METHODS We searched multiple online databases from inception until March 25, 2015, without restrictions on language, date, or location of publication. We included controlled trials conducted in persons with RA and depression or anxiety. Two independent reviewers extracted information including trial and participant characteristics. The standardized mean differences (SMDs) of depression or anxiety scores at postassessment were pooled between treatment and comparison groups, stratified by active versus inactive comparators. RESULTS From 1291 unique abstracts, we included 8 RA trials of depression interventions (6 pharmacological, 1 psychological, 1 both). Pharmacological interventions for depression with inactive comparators (n = 3 trials, 143 participants) did not reduce depressive symptoms (SMD, -0.21; 95% confidence interval [CI], -1.27 to 0.85), although interventions with active comparators (n = 3 trials, 190 participants) did improve depressive symptoms (SMD, -0.79; 95% CI, -1.34 to -0.25). The single psychological trial of depression treatment in RA did not improve depressive symptoms (SMD, -0.44; 95% CI, -0.96 to 0.08). Seven of the trials had an unclear risk of bias. CONCLUSIONS Few trials examining interventions for depression or anxiety in adults with RA exist, and the level of evidence is low to moderate because of the risk of bias and small number of trials.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.", "author" : [ { "dropping-particle" : "", "family" : "Fiest", "given" : "Kirsten M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hitchon", "given" : "Carol A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bernstein", "given" : "Charles N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peschken", "given" : "Christine A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Walker", "given" : "John R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graff", "given" : "Lesley A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zarychanski", "given" : "Ryan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abou-Setta", "given" : "Ahmed", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Patten", "given" : "Scott B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sareen", "given" : "Jitender", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bolton", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marrie", "given" : "Ruth Ann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "CIHR Team \u201cDefining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Rheumatology", "id" : "ITEM-2", "issued" : { "date-parts" : [ [ "2017", "2", "17" ] ] }, "page" : "1", "title" : "Systematic review and meta-analysis of interventions for depression and anxiety in persons with rheumatoid arthritis", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1002/14651858.CD007503.pub2.", "PMID" : "20238354", "abstract" : "BACKGROUND: There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill's Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. OBJECTIVES: To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. SEARCH STRATEGY: Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. SELECTION CRITERIA: Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. DATA COLLECTION AND ANALYSIS: The primary outcome was efficacy 6-8 weeks after randomisation. Data were also extracted at three additional time-points (4-5 weeks, 9-18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop-outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. MAIN RESULTS: Fifty-one studies including 3603 participants were included in the review. Forty-four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80-3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time-points. At\u2026", "author" : [ { "dropping-particle" : "", "family" : "Rayner", "given" : "Lauren", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Price", "given" : "Annabel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Evans", "given" : "Alison", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Valsraj", "given" : "Koravangattu", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Higginson", "given" : "Irene J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hotopf", "given" : "Matthew", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Cochrane Database of Systematic Reviews", "id" : "ITEM-3", "issue" : "17", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "CD007503", "title" : "Antidepressants for depression in physically ill people", "type" : "article" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[35\u201337]", "plainTextFormattedCitation" : "[35\u201337]", "previouslyFormattedCitation" : "[34\u201336]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[35–37]. Future research examining the impact of mental health intervention for physical health outcomes may identify whether effectively managing depression can improve treatment response in RA. Key MessagesDepression at baseline contributes to approximately 30% reduced odds of good biologics treatment response. Depression is associated with reduced change in DAS28 over time in response to biologics.Financial AcknowledgementThis paper represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or the British Society for Rheumatology. The BSRBR-RA is a UK-wide national project to investigate the safety of biologic agents in routine medical practice. This work was supported by the British Society for Rheumatology (BSR), which receives restricted income from UK pharmaceutical companies, presently Abbvie, Celltrion, Hospira, Pfizer, UCB, Samsung and Roche, and in the past Swedish Orphan Biovitrum and MSD. All decisions concerning analyses, interpretation and publication are made autonomously of any industrial contribution.Conflict of InterestThe authors disclose no conflict of interestReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY [1]Matcham, F., Rayner, L., Steer, S. and Hotopf, M. (2013) The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford, England), 52, 2136–48. [2]Matcham, F., Norton, S., Scott, D.L., Steer, S. and Hotopf, M. (2016) Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial. Rheumatology (Oxford, England), 55, 268–78. 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