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Supplementary Table 1. Longitudinal studies reporting absenteism in relation to treatment with TNF inhibitors in patients with Crohn’s diseaseAuthorYear StudyStudy, population ExposureTime point of assessmentAssessment of outcomeResultsLichtenstein 2004ACCENT IN=573Long-term dosing or single dose IFX0-54 weeksQuestionnaireUnemployment rate at baseline 38%. In patients who were unemployed at baseline, 31% were employed at 54 weeks if remission was achieved (35-40%), compared to 16% of those not in remission.Lichtiger 2010,CHOICE N=673 patients who failed IFX treatment17% IFX primary non-responders 83% IFX primary respondersAdalilumab every 2 weeks4, 8, 12, 24 weeksWPAI:CDMean change from baseline in absenteeism was -8.3, -6.5, -7.5, -7.2Feagan, 2010PRECISE Responders at week 4 n=425 (64%)Active treatment n=215Placebo n=210Certolizumab every 4 weeks06, 16, 26 weeks Work Productivity and ActivityImpairment for CD questionnaireWork Productivity and ActivityImpairment for CD questionnaireWPAI:CDScore of absenteism was 10% lower from induction to 26 weeks in treated patients compared to placeboFeagan, 2011WELCOME N=334 (62%)responders at week 6Certolixumab every 2 or 4 weeks 0-26 weeksWPAI:CD Absenteism dropped from 25% to 6% and from 23% to 11% Panaccione2011ACCESSN=304IFX experienced n=160Anti-TNF naive n=144Adalilumab every 2 weeks0-6 monthsWPAI:CDMean change in absenteeism:12 weeks: ?8.8 points for the anti-TNF-naive group4 weeks ?7.2 points, 8 weeks ?9.2 points, 24 weeks ?7.6 points for the infliximab-experienced group.At the final visit, 69% of patients were employed compared with 64% at baselineBinion,2011ACCESS, CARE, CHOICE, EXTENDMeta-analysis N=1,202Adalilumab every 2 weeks? 0-20 weeks (CARE), 0-24 weeks (ACCESS and CHOICE) 0- 52 weeks (EXTEND)WPAI:CDPooled estimates (95% CIs) for absenteeism: -9% (-10% to -7%) Steenholdt,2015N=69 with IFX treatment failure Intensified IFX regimen (n = 36) Personalized treatment defined by IFX and anti-IFX antibodies (n = 33)0-6 monthsWPAI:CDAbsenteeism in employed individuals (n=38) was negligible during the entire study period.Louis2013CAREN=945N=785 (83%) completed 20 weeks Adalimumab every 2 weeks 0, 2, 4, 8, 12, 20 weeksWPAI:CDMean change from baseline in absenteeism was -9.6 at 4 weeks (N=353) and -9.8 at 20 weeks (N=328)Saro 2017EFICA- DEC N=126 bio-na?ve patientsAdalimumab according to clinical practice1, 3, 6, 9, and 12 monthsWPAI:CDCD-caused absenteeism > 50% decreased from 1/3 to 1/10 from baseline to 12 monthsCurrent study 2019N=853 bio-na?ve patients and N=326 patients starting 2nd line treatmentAny TNF inhibitor-6 months to 18 monthsLost workdays according to the Social Insurance Agency 7%-8% reduction in absenteeism from start of treatment to week 24 in bio-na?ve patients and 1%-6% reduction in absenteeism for second line treatmentSupplementary Table 2. ICD-codes that, if occurring before Jan 1st 2007, excluded the patient from participation in the studyICD-7ICD-8ICD-9ICD-101964-19681969-19861987-19961997-Ulcerative colitis (UC)572,20 ; 572,21; 578,03563,10 ; 563,99 ; 569,02556K51Crohn’s disease (CD)572,00 ; 572,09563,00555K50IBD unclassified (IBD-U)UC+CDUC+CDUC+CDUC + CD, or K52.3Supplementary Table 3. ICD codes for medication used in patients with Crohn’s diseaseDrug groupSubstanceATC-codeConversion factor to Prednisolon equivalents*ImmunomodulatorsAzathioprineL04AX01MercaptopurineL01BB02MethotrexateL04AX03/L01BA01BiologicsInfliximabL04AB02 (L04AA12 before 2008)AdalimumabL04AB04 (L04AA17 before 2008)GolimumabL04AB06VedolizumabL04AA33CertolizumabL04AB05UstekinumabL04AC05Oral corticosteroidsBetamethasoneH02AB018.33DexamethasoneH02AB026.67MethylprednisoloneH02AB041.25PrednisoloneH02AB061PrednisoneH02AB071Aminosalicylates (5-ASA)SulfasalazineA07EC01MesalazineA07EC02OlsalazineA07EC03BalsalazideA07EC04* Conversion calculated according to Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy.?Allergy Asthma Clin Immunol 2013;9:30.Supplementary table 4. Surgical procedure codesSurgical procedure7th rev(KK?97)Intestinal surgeryIleocecal resectionJFB20, JFB21, JFB30, JFB31, JFB33, JFB34Small bowel resectionJFB00, FFB01ColectomyJFH00, JFH01, JFH10, JFH11, JFH20, JFH96, JFH30Segmental colon resectionJFB40, JFB41, JFB43, JFB44, JFB46, JFB47, JFB50, JFB51, JFB60, JFB61, JFB63, JFB64, JGB00, JGB01, JGB10, JGB11ProctectomyJFH20, JGB30, JGB31, JGB40, JGB96, JGB97Other bowel surgeryStrictureplasty JFA60, JFA63Enterorraphy JFA70, JFA71, JFA80, JFA81Closure of fistulaJFA76, JFA86Other intestinal resectionJFB96, JFB97Intestinal anastomosis and by-passJFC00, JFC01, JFC10, JFC11, JFC20, JFC21, JFC30, JFC31, JFC50, JFC51Formation of stomaJFF10, JFF11, JFF13, JFF16, JFF23, JFF24, JFF26, JFF27, JFF30, JFF31, JFF96, JFF97Operations on intestinal stoma or reservoirJFG40, JFG50, JFG53, JFG56, JFG60, JFG73, JFG76, JFG80, JFG83, JFG86, JFG96Other intestinal surgeryJFW96, JFW97Ileoanal anastomosisJGB50, JGB60, JFH30, JFH33, JFH40Ileorectal anastomosisJFC40, JFC41Perianal surgeryPerianal incision and drainageJHA00Dilatation of the anal sphincterJHD00Lay open or excision of perianal fistulaJHD20Partial lay open or excision of perianal fistula (including seton placement)JHD30Completion lay open or excision of perianal fistulaJHD33Excision of perianal fistula with advancement flapJHD50Occlusion of perianal fistula with collagen plugJHD60Occlusion of perianal fistula with fibrin glueJHD63Other anal or perianal surgery (e.g. examination under anesthesia)JHW96Supplementary table 5. ICD codes for extraintestinal manifestationsICD-10Primary Sclerosing CholangitisK83.0Cutaneous manifestationsErythema nodosumL52Pyoderma gangraenosumL88Sweet syndromeL98.2Ocular manifestationIridocyclitisH20Joint manifestationsArthropaty in Crohn’s diseaseM07.4Arthropaty in Ulcerative colitisM07.5Other defined arthropathy in gastrointestinal disordersM07.6Juvenile arthritis in Crohn’s diseaseM09.1Juvenile arthritis in Ulcerative colitisM09.2Bechterew’s diseaseM45Spondylarthritis, inflammatory NODM460, M461, M468, M469Arthritis NODM139, M255Supplementary table 6. ICD codes for Montreal classification. Patients’ phenotypes were defined by the highest available degree of anatomic distribution of inflammation. Patients who were never diagnosed with a code representing a specific location were classified as LX.Montreal classificationDiagnostic codesLocationL1 Small bowel disease or terminal ileitisK50.0L2ColonK50.1L3/LXIleocecal Crohn’s disease or location not definedK50.8, K50.9BehaviorB1 Non-stricturing, non-penetratingNone of the ICD-codes for B2 or B3.B2StricturingCrohn’s disease AND any of the following codes (K56.5; K56.6; K56.7; K62.4)B3PenetratingCrohn’s disease AND any of the following diagnostic codes (K63.0, K63.2, K31.6, N82.2, N82.3, N82.4) OR any of the following surgical procedure codes (JFA76, JFA86).PPerianal disease Crohn’s disease AND any of the following diagnostic codes: (K60.3, K60.4, K60.5, K61.0, K61.1, K61.2, K61.3, K61.4, K62.4) OR any of the following surgical procedure codes: (JHD20, JHD30, JHD33, JHD50, JHD60, JHD63, JHA00, JHD00, JHW96)Supplementary Table 7. Characteristics of working-age patients with Crohn’s disease diagnosed July 1st 2006- Sep 30th 2013 and matched population comparators subjects Patients with Crohn’s diseasePopulation comparator subjectsP-valueN3,95619,716Sex, n (%)0.97Men, n (%)1,926 (49)9,590 (49)Women, n (%)2,030 (51)10,126 (51)Age at diagnosis/matchMedian (25th-75th; min-max) years34 (25-46;19-59)34 (25-46;19-59)0.87Categories, n (%)1.0019-29 years1,572 (40)7,853 (40)30-39 years810 (20)4,047 (21)40-49 years839 (21)4,178 (21)50-59 years735 (19)3,638 (18)Education, n (%)0.699 years596 (15)2,974 (15)10-12 years2,107 (53)10,531 (53)≥12 years1,187 (30)5,932 (30)unknown66 (1.7)279 (1.4)Follow-up time Median (25th-75th; min-max) years5.3 (3.6-7.1;0-9.2)5.4 (3.6-7.1;0-9.2)0.11Death during follow-up n (%)66 (1.7)106 (0.54)<0.0001Medication for Crohn’s disease, n(%)Aminosalicylates1547 (39)Immunomodulators2,043 (52)Systemic corticosteroids2,560 (65)TNF inhibitors853 (22)Surgery for Crohn’s disease, n (%)Any intestinal surgery719 (18)Ileocecal or small bowel resection621 (16)Partial or total colectomy 140 (3.5)Other intestinal surgery704 (18)Perianal surgery 276 (7.0)Supplementary Table 8. Mean number of lost workdays from 6 months before to 18 months after start of treatment with aminosalicylate, immunomodulator, TNF inhibitor, and intestinal surgery in all patients starting treatment (first column), and in patients not requiring additional or other treatment (second column)AminosalicylateImmunomodulator1st line TNF inhibitor2nd line TNF inhibitorIntestinal surgeryStarting treatmentMean days (95% CI)Continuing treatmentMean days (95% CI)Starting treatmentMean days (95% CI)Continuing treatmentMean days (95% CI)Starting treatmentMean days (95% CI)Continuing treatmentMean days (95% CI)Starting treatmentMean days (95% CI)Continuing treatmentMean days (95% CI)Starting treatmentMean days (95% CI)Continuing treatmentMean days (95% CI)-6 3.66 (3.15-4.17)3.66 (3.19-4.12)3.83 (3.45-4.22)3.83 (3.42-4.25)4.42 (3.82-5.03)4.42 (3.72-5.11)5.56 (4.49-6.63)5.56 (4.51-6.61)5.54 (4.83-6.25)5.54 (4.75-6.33)-3 4.36 (3.87-4.86)4.36 (3.93-4.80)4.63 (4.19-5.07)4.63 (4.20-5.07)5.63 (4.95-6.32)5.63 (4.90-6.37)6.06 (4.92-7.20)6.06 (4.93-7.19)6.78 (6.02-7.55)6.78 (6.02-7.55)06.21 (7.72-6.70)6.21 (5.67-6.75)6.46 (5.93-6.99)6.18 (5.66-6.71)7.24 (6.51-7.97)7.20 (6.34-8.07)6.15 (4.99-7.30)5.85 (4.68-7.01)16.9 (16.1-17.7)16.5 (15.6-17.3)34.60 (4.12-5.08)4.11 (3.62-4.60)4.89 (4.41-5.37)4.45 (3.99-4.90)5.48 (4.70-6.26)5.06 (4.37-5.75)5.76 (4.55-6.98)4.57 (3.27-5.87)7.19 (6.28-8.09)6.84 (5.83-7.86)64.44 (3.95-4.93)4.00 (3.44-4.56)4.37 (3.93-4.80)4.00 (3.53-4.47)5.17 (4.47-5.87)4.83 (4.07-5.59)5.69 (4.32-7.06)3.98 (2.38-5.59)6.36 (5.51-7.21)5.92 (4.99-6.85)94.27 (3.72-4.81)3.79 (3.23-4.35)4.16 (3.72-4.61)3.83 (3.42-4.23)4.93 (4.13-5.73)4.26 (3.54-4.99)5.65 (4.32-6.98)3.24 (1.85-4.64)6.21 (5.36-7.05)5.63 (4.73-6.52)124.25 (3.78-4.72)3.80 (3.23-4.37)4.12 (3.67-4.56)3.53 (3.05-4.02)4.87 (4.05-5.69)4.19 (3.51-4.88)6.14 (4.56-7.72)3.50 (1.84-5.16)5.81 (4.87-6.75)5.23 (4.18-6.28)154.04 (3.51-4.58)3.63 (3.04-4.23)3.97 (3.55-4.40)3.46 (3.00-3.92)4.48 (3.85-5.11)3.74 (2.97-4.51)5.46 (3.92-7.01)3.52 (1.82-5.23)5.28 (4.41-6.16)4.75 (3.88-5.62)183.94 (3.43-4.44)3.67 (3.09-4.24)3.84 (3.42-4.25)3.36 (2.89-3.84)4.52 (3.84-5.19)3.80 (3.04-4.56)5.31 (4.09-6.53)3.02 (1.60-4.44)4.71 (3.86-5.56)4.28 (3.44-5.12)Supplementary Figure 1. Flow-chart of participants and registers usedSupplementary Figure 2. Mean number of lost workdays per month from 6 months before to 18 months after start of TNF inhibitor in patients and matched population comparators in subgroups stratified for sex (men/women), age (19-39, 40-49, 50-59 years), and education (9, 10-12, >12 years)Supplementary Figure 3. Mean number of lost workdays per month from 6 months before to 18 months after start of aminosalicylate in patients and matched population comparators in subgroups stratified for sex (men/women), age (19-39, 40-49, 50-59 years), and education (9, 10-12, >12 years)Supplementary Figure 4. Mean number of lost workdays per month from 6 months before to 18 months after start of immunomodulator in patients and matched population comparators in subgroups stratified for sex (men/women), age (19-39, 40-49, 50-59 years), and education (9, 10-12, >12 years)Supplementary Figure 5. Mean number of lost workdays per month from 6 months before to 18 months after intestinal surgery in patients and matched population comparators in subgroups stratified for sex (men/women), age (19-39, 40-49, 50-59 years), and education (9, 10-12, >12 years) ................
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