Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA)

Ann Rheum Dis. 2016 May;75(5):855-61. doi: 10.1136/annrheumdis-annrheumdis-2014-206747. Epub 2015 Apr 29.

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.

Keywords: Autoimmune Diseases; DMARDs (biologic); Infections; Juvenile Idiopathic Arthritis; Methotrexate.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / adverse effects*
  • Adalimumab / therapeutic use
  • Adolescent
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / epidemiology
  • Autoimmune Diseases / chemically induced
  • Biological Products / adverse effects
  • Biological Products / therapeutic use
  • Child
  • Etanercept / adverse effects*
  • Etanercept / therapeutic use
  • Female
  • Germany / epidemiology
  • Humans
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / epidemiology
  • Male
  • Methotrexate / adverse effects
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology
  • Opportunistic Infections / chemically induced
  • Opportunistic Infections / epidemiology
  • Prospective Studies
  • Registries
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Uveitis / chemically induced
  • Uveitis / epidemiology

Substances

  • Antirheumatic Agents
  • Biological Products
  • Tumor Necrosis Factor-alpha
  • Adalimumab
  • Etanercept
  • Methotrexate