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Extended report
Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA)
  1. Jens Klotsche1,2,
  2. Martina Niewerth1,
  3. Johannes-Peter Haas3,
  4. Hans-Iko Huppertz4,
  5. Angela Zink1,5,
  6. Gerd Horneff6,
  7. Kirsten Minden1,7
  1. 1German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany
  2. 2Charité Universitätsmedizin Berlin, Institute for Social Medicine, Epidemiology and Health Economics, Berlin, Germany
  3. 3German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany
  4. 4Professor Hess Children's Hospital, Bremen, Germany
  5. 5Charité Universitätsmedizin Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany
  6. 6Asklepios Kinderklinik Sankt Augustin GmbH, Sankt Augustin, Germany
  7. 7Charité Universitätsmedizin Berlin, Children's university hospital, Berlin, Germany
  1. Correspondence to Dr Jens Klotsche, German Rheumatism Research Centre, a Leibniz Institute, Chariteplatz 1, Berlin 10117, Germany; Jens.Klotsche{at}


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.

  • DMARDs (biologic)
  • Methotrexate
  • Juvenile Idiopathic Arthritis
  • Infections
  • Autoimmune Diseases

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