Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist

Objective. To evaluate the efficacy and safety of interleukin-l receptor an tagonist (IL-1Ra) in patients with rheumatoid arthritis (RA), Methods. Patients with active and severe RA (disease duration <8 years) wer e recruited into a 24-week, double-blind, randomized, placebo-controlled, m ulticenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (less than or equal to 10 mg prednisolone daily) remained c onstant throughout the study. Any disease-modifying antirheumatic drugs tha t were being administered were discontinued at least 6 weeks prior to enrol lment. Patients were randomized to 1 of 4 treatment groups: placebo or a si ngle, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg, Results. A total of 472 patients were recruited. At enrollment, the mean ag e, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical pa rameters of disease activity were similar in each treatment group and were consistent with active and severe RA, At 24 weeks, of the patients who rece ived 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criter ia for response (the primary efficacy measure), 44% met the Paulus criteria , and statistically significant improvements were seen in the number of swo llen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnair e score, C-reactive protein level, and erythrocyte sedimentation rate, In a ddition, the rate of radiologic progression in the patients receiving IL-1R a was significantly less than in the placebo group at 24 weeks, as evidence d by the Larsen score and the erosive joint count. IL-1Ra was well tolerate d and no serious adverse events were observed. An injection-site reaction w as the most frequently observed adverse event, and this resulted in a 5% ra te of withdrawal from the study among those receiving IL-1Ra at 150 mg/day, Conclusion. This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the fir st biologic agent to demonstrate a beneficial effect on the rate of joint e rosion.