Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial

Arthritis Rheum. 2011 Jun;63(6):1543-51. doi: 10.1002/art.30223.


Objective: Etanercept, a fully human tumor necrosis factor (TNF) receptor, is an effective treatment in patients with ankylosing spondylitis (AS). Sulfasalazine is frequently used for the treatment of both axial symptoms and peripheral symptoms of AS, and it has been the recommended therapy before the use of an anti-TNF agent when peripheral arthritis is present. Until now, no clinical trial has compared the efficacy and safety of a TNF blocker with that of sulfasalazine. This study was undertaken to compare the efficacy and safety of etanercept with that of sulfasalazine after 16 weeks of treatment in patients with axial and peripheral manifestations of AS.

Methods: In this randomized, double-blind study, patients received etanercept 50 mg once weekly (n=379) or sulfasalazine titrated to a maximum of 3 gm/day (n=187) for 16 weeks. The primary end point was the proportion of patients who achieved the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) at 16 weeks. Last observation carried forward was predefined for imputation of missing values.

Results: The mean age of the patients was 41 years, 74% were male, and the mean disease duration was 7.6 years. The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine (75.9% versus 52.9%; P<0.0001). As early as week 2 of treatment, etanercept was found to be more effective than sulfasalazine (P<0.0001) in ameliorating both the axial symptoms and peripheral manifestations. Serious adverse events rarely occurred, and the rate of serious adverse events did not differ between groups.

Conclusion: In this population of patients with AS, etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints.

Trial registration: NCT00247962.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Double-Blind Method
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / therapeutic use*
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Spondylitis, Ankylosing / drug therapy*
  • Sulfasalazine / adverse effects
  • Sulfasalazine / therapeutic use*
  • Treatment Outcome


  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Sulfasalazine
  • Etanercept

Associated data