Effects of anakinra monotherapy on joint damage in patients with rheumatoid arthritis. Extension of a 24-week randomized, placebo-controlled trial

Objective. To determine the effects of treatment on the radiologic manifestations of joint damage in patients with rheumatoid arthritis (RA) who participated in a 24-week extension study of a randomized, placebo-controlled clinical trial of anakinra, a recombinant human interleukin I receptor antagonist. Methods. The patients had entered a 24-week, randomized, double-blind, placebo-controlled study. Anakinra was self-administered by subcutaneous injection of 30, 75, or 150 mg/day. Upon completion of the placebo-controlled phase, the patients entering the extension study who had received placebo were randomized to one of the 3 treatment dosages for a further 24 weeks, and the patients who had been initially randomized to one of the 3 anakinra dosages continued to receive the same dosage. Radiographs of the hands were obtained at baseline and at 24 and 48 weeks. The radiographs were evaluated using a modified Sharp method. Results. A total of 472 patients were recruited. The mean change in the total modified Sharp score of 178 patients who completed 48 weeks treatment, including all dosages, was significantly less than the change observed in 58 patients who received placebo for 24 weeks and anakinra for 24 weeks (p = 0.015). A significant reduction in the change of the total modified Sharp score was observed in the patients who received anakinra 75 and 150 mg/day. The-total modified Sharp score was reduced significantly more during the second 24-week treatment period, compared to the first (p < 0.001). Significant reductions in the second 24-week period were observed following anakinra 75 mg/day (p = 0.006) and 150 mg/day (p = 0.008). Conclusion. Patients with RA who received anakinra. for 48 weeks demonstrated significant slowing of radiographic joint damage. The treatment effect observed after the first 24-week period appeared to increase when anakinra. was continued for 48 weeks.