Do tumor necrosis factor inhibitors cause uveitis? A registry-based study

Arthritis Rheum. 2007 Oct;56(10):3248-52. doi: 10.1002/art.22918.

Abstract

Objective: Population-based studies of patients with ankylosing spondylitis indicate that tumor necrosis factor (TNF) inhibitors prevent uveitis. Paradoxically, anecdotal reports implicate etanercept as a cause of uveitis. Therefore, using the information from 2 drug events databases, the purpose of this study was to assess reported cases of uveitis associated with the use of TNF inhibitors.

Methods: Uveitis cases occurring in the US associated with etanercept, infliximab, or adalimumab therapy that were reported to 2 spontaneous reporting databases prior to January 1, 2006 were reviewed.

Results: Overall, there were 43 cases of uveitis associated with etanercept, 14 associated with infliximab, and 2 associated with adalimumab. After normalizing for the estimated number of patients treated with each medication, etanercept was associated with a greater number of uveitis cases than infliximab (P < 0.001) and adalimumab (P < 0.01), while no such association was found between adalimumab and infliximab (P > 0.5). Using a priori criteria to avoid including patients whose underlying disease was associated with uveitis, 20 cases associated with etanercept, 4 cases associated with infliximab, and 2 cases associated with adalimumab were identified. A repeat analysis again revealed a greater number of uveitis cases associated with etanercept (P < 0.001 versus infliximab).

Conclusion: Etanercept therapy is associated with a significantly greater number of reported uveitis cases in comparison with infliximab and adalimumab in 2 medication side effect registries. These results are consistent with previous studies and suggest that this relationship is drug specific and not related to TNF inhibitors as a whole. However, our findings do not support the use of infliximab over etanercept; rather, if a patient develops uveitis during etanercept therapy, then a change to infliximab may be warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Anti-Inflammatory Agents / adverse effects*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects
  • Infliximab
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor
  • Registries*
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / adverse effects*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Uveitis

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept