Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis

Objective: To assess the efficacy and safety of leflunomide in active ankylosing spondylitis (AS) compared with placebo in a 24 week pilot study. Methods: In a single centre randomised, double blind, placebo controlled study, 45 patients with active AS were randomised to either leflunomide 20 mg daily (n = 30) or placebo (n = 15). Active disease was defined as a score of >= 4 on the Bath ankylosing spondylitis disease activity index (0-10), and pain of >= 4 on a visual analogue scale (0-10). The primary efficacy variable at week 24 was the 20% response rate, as recommended by the Assessments in Ankylosing Spondylitis (ASAS) working group. Secondary outcome variables included general wellbeing, metrology index, swollen joint count, erythrocyte sedimentation rate, and C reactive protein. Results: In all, 13 women and 32 men were studied. Demographic and disease indices were comparable between the two treatment groups at baseline. The rate of ASAS 20% responders was not significantly different: 27% in the leflunomide treated patients and 20% in the placebo group (95% confidence interval, -32% to 19%). No significant differences were found between the treatment groups in mean changes of the secondary outcome variables. Eleven patients were withdrawn prematurely from the study because of adverse events (7), lack of efficacy (3), and non-compliance (1). Most frequently adverse events were gastrointestinal side effects and skin disorders. Conclusions: In this placebo controlled study, leflunomide treatment did not result in a significant improvement of the ASAS 20% response in active ankylosing spondylitis. No unexpected or severe adverse events occurred.