Treatment of Ankylosing Spondylitis with Etanercept (Enbrel®)
Unchanged for over a decade, the standard of care for ankylosing spondylitis has been a combination of physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs) and unproven agents such as sulfasalazine and methotrexate. However, recent studies have demonstrated the efficacy of infliximab in the treatment of ankylosing spondylitis (see article). Adding to these findings, Gorman et al (NEJM 346:1349-56, 2002) found that a four month course of etanercept resulted in significant and sustained improvement in patients with ankylosing spondylitis.
Methods: Forty patients with active ankylosing spondylitis were entered into a randomized, double-blind, placebo-controlled trial. Patients received either a twice-weekly 25 mg dose of etanercept or placebo for four months. Patients were allowed to take NSAIDs, oral corticosteroids (<= 10 mg/day) and disease-modifying antirheumatic drugs (DMARDs) at stable doses during the trial.
Results: Patients in the etanercept group showed significant improvement from baseline compared to patients in the placebo group in many measures of disease activity including C-reactive protein, erythrocyte sedimentation rate, morning stiffness, spinal pain, quality of life and functioning. At the end of the four month trial, 80% of patients in the etanercept group had improved clinically compared with 30% of patients in the placebo group (P=0.004).
Conclusion: Etanercept appears to be a potent agent in the treatment of ankylosing spondylitis. Clinical improvements are quickly observable and are sustained over time. Further studies with larger numbers of patients are needed to determine the effects of etanercept on the progression of ankylosing spondylitis.
Editorial Comment: Although the study design and outcomes differ somewhat from a recently published trial in ankylosing spondylitis with another TNF inhibitor (infliximab), the results in the two trials are very similar. Etanercept is associated with a clear clinical response. Whether it will slow disease progression remains to be seen and will be dependent on identification of measures to evaluate this long-term outcome. The mechanism by which TNF inhibition works in this disease is less clear than in rheumatoid arthritis.