Inflammatory Bowel Disease in Juvenile Idiopathic Arthritis Patients Treated with Biologics

Barthel, D.; Ganser, Gerd; Kuester, Rolf‐Michael; Onken, N.; Minden, Kirsten; Girschick, Hermann; Hospach, Anton; Horneff, Gerd

doi:10.3899/jrheum.140472

Cited by 52 publications

(66 citation statements)

References 38 publications

(49 reference statements)

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“…In a British cohort, medically important infections occurred more frequently among users of TNF inhibitors than in a non-biologic control cohort, but the rate of serious infections was not significantly different [25]. Interestingly, new onset Crohn’s disease or ulcerative colitis mostly occurred in the etanercept cohort, which is consistent with previous findings [26]. Etanercept has been shown to lack efficacy toward CED [27].…”

Section: Discussionsupporting

confidence: 78%

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

et al. 2016

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BackgroundTreatment response, remission rates and compliance in patients with polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab, etanercept, or tocilizumab were analyzed in clinical practice.MethodsData collected in the German BIKER registry were analyzed in patients with polyJIA who started treatment with approved biologics, adalimumab, etanercept or tocilizumab, from 2011 to 2015. Baseline patient characteristics, treatment response, safety and drug survival were compared.ResultsTwo hundred thirty-six patient started adalimumab, 419 etanercept and 74 tocilizumab, with differences in baseline patient characteristics. Baseline Juvenile Disease Activity Score (JADAS)10 (mean ± SD) in the adalimumab/etanercept/tocilizumab cohorts was 12.1+/−7.6, 13.8 ± 7.1 and 15.1 ± 7.4, respectively (adalimumab vs etanercept, p = 0.01), and Childhood Health Assessment Questionnaire (CHAQ)-disability index scores was 0.43 ± 0.58, 0.59 ± 0.6 and 0.63 ± 0.55, respectively (adalimumab vs etanercept, p < 0.001). Uveitis history was more frequent in the adalimumab cohort (OR 5.73; p < 0.001). Balanced patients’ samples were obtained by a generalized propensity score to adjust for baseline differences. Pediatric ACR30/50/70/90 criterion improvement after 3 months treatment was achieved by 68%/60%/42%/24% in the etanercept cohort, 67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26% in the tocilizumab cohort. At 24 months, JADAS minimal disease activity was achieved in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients in the adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was used in 95.5% of patients as a first biologic, adalimumab in 50.8% and tocilizumab in 20.2%. There were no important differences in efficacy between first-line and second-line use of biologics. In total 60.4%/49.4%/31.1% patients discontinued adalimumab/etanercept/tocilizumab, respectively (HR for adalimumab 1.67; p < 0.001; HR for tocilizumab 0.35; p = 0.001). Drug survival rates did not differ significantly in patients on biologic monotherapy compared with combination therapy with methotrexate. Over 4 years observation under etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and 148/119/26 serious adverse events, respectively, were reported.ConclusionsIn clinical practice, etanercept is most frequently used as first-line biologic. Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA. Overall, tolerance was acceptable. Interestingly, compliance was highest with tocilizumab and lowest with adalimumab. This study provides the first indication for the comparison of different biologic agents in polyarticular JIA based on observational study data with all their weaknesses and demonstrates the need for well-controlled head-to-head studies for confirmation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1170-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 78%

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

et al. 2016

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“…In patients treated with MTX, the IBD incidence was comparable to patients treated with MTX and etanercept in combination but was significantly lower compared to JIA patients without MTX. Etanercept monotherapy but not combination of etanercept and MTX was associated with an increased incidence of IBD [26]. A total of 78 uveitis events (1.9/100 patient-years) were reported as an AE upon etanercept use.…”

Section: Registry Datamentioning

confidence: 93%

“…No case of tuberculosis or other opportunistic infection was reported while 18 patients (0.4/100 patient-years) had at least 1 incidence of Herpes zoster, which was significantly more frequent than in the non-biologic control cohort with 5 events (0.2/100 patient-years) [25]. In 12 patients, inflammatory bowel disease (IBD) occurred upon etanercept compared to 3 cases in the control cohort not exposed to biologics [26]. Upon etanercept administration, 8 patients developed Crohn's disease and 4 ulcerative colitis.…”

Section: Registry Datamentioning

confidence: 95%

Safety of biologic therapies for the treatment of juvenile idiopathic arthritis

Horneff

2015

Expert Opinion on Drug Safety

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The safety profiles of approved biologics, the TNF-α inhibitors etanercept and adalimumab, and the IL-6-inhibitor tocilizumab are highly acceptable. This conclusion is not easily expandable to the IL-1 inhibitor canakinumab as well as the T-cell-activation-inhibitor abatacept due to lack of experience; however, both have showed an excellent safety profile so far. An increase in knowledge about risk profiles in national and international collaborations, with national as well as international registries, is necessary.

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“…О необходимости сочетанной терапии этанерцеп-том и метотрексатом свидетельствуют факты, что имен-но такая комбинация уменьшает риски случаев увеи-та и воспалительных заболеваний кишечника de novo по сравнению с монотерапией метотрексатом [32,33]. В исследовании I. Foeldvari и соавт.…”

Section: вопросы современной педиатрииunclassified

Etanercept Treatment Results in Children With Non-Systemic Juvenile Idiopathic Arthritis: Remission, Recrudescence, and Adverse Events. Retrospective Cohort Study

Костик¹,

Чикова²,

Исупова³

et al. 2018

Vopr. sovr. pediatr.

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Background.Etanercept is a biological drug most commonly used in patients with juvenile idiopathic arthritis (JIA). The results of its use are showed in local studies.Objective.Our aim was to evaluate the efficacy and safety of the use of etanercept in children with non-systemic JIA, to determine the predictors of remission and the risk factors for the development of exacerbations.Methods.In a retrospective cohort study, the results of etanercept treatment (remission, exacerbations, adverse events) in children with non-systemic JIA were analyzed. The minimum follow-up period was 6 months.Results.The period of remission within 6–36 months occurred in 77/131 (58.8%), exacerbations developed in 18/129 (14.0%) patients. Predictors of achieving remission were the age of JIA onset < 8 years [relative risk (RR) 2.05; 95% confidence interval (CI) 1.27–3.23], the age of prescribing etanercept ≤ 10 years (RR 1.7, 95% CI 1.22–2.38), the time of the disease prior to etanercept prescription < 2.5 years (RR 2.4, 95% CI 1.4–4.4), the presence of HLA-B27 antigen (RR 2.15, 95% CI 0.98–4.75; p = 0.06). The risk of exacerbations was higher in children with polyarticular JIA (RR 2.7, 95% CI 0.9–8.2; p = 0.08), whereas methotrexate therapy reduced the risk of exacerbations (RR 0.32, 95% CI 0.1–1.15; p = 0.05). Etanercept was discontinued due to primary (improvement by the ACRpedi criteria after 3 months of therapy <30%) or secondary (loss of previously achieved ≥ 30% improvement) failure in 14/152 (9.2%) patients; de novo uveitis developed in 8/152 (5.3%) patients; reactions at the injection site — in 6/152 (4.0%) patients.Conclusion.Therapy involving etanercept is more likely to induce remission in younger patients with JIA onset at the age of 8 years and a history of less than 2.5 years. A high risk of exacerbations was noted in patients with polyarticular JIA, and low one — in those receiving methotrexate as a part of combined therapy.

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Inflammatory Bowel Disease in Juvenile Idiopathic Arthritis Patients Treated with Biologics

Abstract: Incidence of IBD in patients with JIA is higher than in the population. MTX turned out to be protective, even in combination with ETN.

Cited by 52 publications

References 38 publications

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

Safety of biologic therapies for the treatment of juvenile idiopathic arthritis

Etanercept Treatment Results in Children With Non-Systemic Juvenile Idiopathic Arthritis: Remission, Recrudescence, and Adverse Events. Retrospective Cohort Study

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