Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha

N Engl J Med. 2002 May 2;346(18):1349-56. doi: 10.1056/NEJMoa012664.


Background: There are few effective treatments for ankylosing spondylitis, which causes substantial morbidity. Because of the central role of tumor necrosis factor alpha in the spondyloarthritides, we performed a randomized, double-blind, placebo-controlled trial of etanercept, a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein, in patients with ankylosing spondylitis.

Methods: Forty patients with active, inflammatory ankylosing spondylitis were randomly assigned to receive twice-weekly subcutaneous injections of etanercept (25 mg) or placebo for four months. The primary end point was a composite of improvements in measures of morning stiffness, spinal pain, functioning, the patient's global assessment of disease activity, and joint swelling. Patients were allowed to continue taking nonsteroidal antiinflammatory drugs, oral corticosteriods (< or =10 mg per day), and disease-modifying antirheumatic drugs at stable doses during the trial.

Results: Treatment with etanercept resulted in significant and sustained improvement. At four months, 80 percent of the patients in the etanercept group had a treatment response, as compared with 30 percent of those in the placebo group (P=0.004). Improvements over base-line values for various measures of disease activity, including morning stiffness, spinal pain, functioning, quality of life, enthesitis, chest expansion, erythrocyte sedimentation rate, and C-reactive protein, were significantly greater in the etanercept group. Longitudinal analysis showed that the treatment response was rapid and did not diminish over time. Etanercept was well tolerated, with no significant differences in rates of adverse events between the two groups.

Conclusions: Treatment with etanercept for four months resulted in rapid, significant, and sustained improvement in patients with ankylosing spondylitis.

Publication types

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

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / therapeutic use*
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Quality of Life
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / physiopathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept