Anakinra for Colchicine-Resistant Familial Mediterranean Fever A Randomized, Double-Blind, Placebo-Controlled Trial

Objective. Familial Mediterranean fever (FMF) is refractory to colchicine prophylaxis in 10-20% of patients. In a number of patient series, treatment with anakinra, an interleukin-1-blocking agent, prevented FMF attacks in those with colchicine-resistant FMF. This study was undertaken to evaluate the efficacy and safety of anakinra in the treatment of colchicine-resistant FMF, using a randomized controlled trial. Methods. Patients with colchicine-resistant FMF receiving colchicine (dosage >= 1.5 to <= 3 mg/day) were recruited and randomly assigned to receive anakinra or placebo (vehicle). The treatment duration was 4 months. Primary efficacy outcomes were the number of attacks per month, and the number of patients with a mean of < 1 attack per month. Quality of life was assessed using a 0-10- grade visual analog scale (VAS), and safety was assessed according to the number and severity of adverse events. Results. Twenty-five patients with colchicineresistant FMF (14 women) were enrolled, of whom 12 were randomized to receive anakinra and 13 to receive placebo. The mean +/- SD number of attacks per patient per month was 1.7 +/- 1.7 in those receiving anakinra and 3.5 +/- 1.9 in those receiving placebo (P=0.037). Six patients in the anakinra group, compared to none in the placebo group, had < 1 attack permonth (P50.005). A beneficial effect of anakinra was noted in the number of attacks in the joints per month in patients receiving anakinra (mean +/- SD 0.8 +/- 1.6 versus 2.1 +/- 1.1 in the placebo group; P=0.019) and in quality of life (mean +/- SD VAS score 7.7 +/- 2.3 in the anakinra group versus 4.2 +/- 2.9 in the placebo group; P=0.045). The number of adverse events per patient per month was comparable between the anakinra group and the placebo group (mean +/- SD 2.03 +/- 1.75 versus 3.34 +/- 2.5; P=0.22). There were no severe adverse events. Conclusion. In this randomized controlled trial, anakinra appears to be an effective and safe treatment for colchicine-resistant FMF.