Jens Klotsche1, Martina Niewerth2, Johannes-Peter Haas3, Hans-Iko Huppertz4, Angela Zink5, Gerd Horneff6, Kirsten Minden7. 1. German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany Charité Universitätsmedizin Berlin, Institute for Social Medicine, Epidemiology and Health Economics, Berlin, Germany. 2. German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany. 3. German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany. 4. Professor Hess Children's Hospital, Bremen, Germany. 5. German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany Charité Universitätsmedizin Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany. 6. Asklepios Kinderklinik Sankt Augustin GmbH, Sankt Augustin, Germany. 7. German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany Charité Universitätsmedizin Berlin, Children's university hospital, Berlin, Germany.
Abstract
IMPORTANCE: Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. OBJECTIVES: To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. DESIGN, SETTING AND PARTICIPANTS: Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. MAIN OUTCOMES AND MEASURES: We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). RESULTS: Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). CONCLUSIONS AND RELEVANCE: Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
IMPORTANCE: Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. OBJECTIVES: To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. DESIGN, SETTING AND PARTICIPANTS: Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritisMethotrexate/Biologics long-term Observation. MAIN OUTCOMES AND MEASURES: We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). RESULTS: Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). CONCLUSIONS AND RELEVANCE: Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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