Scleritis: a paradoxical effect of etanercept? Etanercept-associated inflammatory eye disease

J Rheumatol. 2012 Feb;39(2):233-9. doi: 10.3899/jrheum.110865. Epub 2011 Dec 15.


Objective: To describe 3 cases of scleritis associated with etanercept use for rheumatoid arthritis (RA) and to review the literature related to inflammatory eye diseases associated with the use of etanercept.

Methods: Three cases of severe scleritis during etanercept therapy were analyzed. A systematic review of the literature in PubMed, Embase, and the Cochrane Library was performed, from 1962 to July 2010.

Results: Three patients with seropositive RA developed scleritis 7-28 months after initiation of etanercept, for the first time during their long-lasting disease. In all patients the underlying disease had responded well to anti-tumor necrosis factor therapy. Ocular inflammation went into remission after discontinuation of etanercept, and no other relapses were observed. One patient experienced a dechallenge-rechallenge phenomenon (improvement in symptoms following discontinuation of the agent, then reappearance or worsening of symptoms on reexposure to the agent). Forty-two cases of inflammatory eye diseases believed to be associated with the use of etanercept have been reported in the literature: 33 uveitis, 8 scleritis, 1 orbital myositis, concerning 16 patients with RA, 10 with juvenile idiopathic arthritis, 14 with ankylosing spondylitis, and 2 with psoriatic spondyloarthropathy. Dechallenge was performed in 28 patients, leading to resolution of symptoms. Rechallenge was done in 6 cases, with clear exacerbation.

Conclusion: Ocular inflammation is paradoxically a potential adverse effect of etanercept, even in previously uninvolved eyes.

Publication types

  • Case Reports
  • Review
  • Systematic Review

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects*
  • Immunoglobulin G / therapeutic use
  • Male
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Rituximab
  • Scleritis / chemically induced*
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Rituximab
  • Adalimumab
  • Etanercept