Rilonacept (IL-1 TRAP) for treatment of colchicine resistant familial mediterranean fever (FMF): a randomized, multicenter double-blinded, alternating treatment trial

Methods Subjects were FMF patients ≥4 years of age recruited at 6 U.S. sites, who had at least 1 FMF attack per month despite receiving adequate doses of, or who were intolerant of colchicine. Subjects received two 3-month courses of rilonacept (Arm A) at 2.2 mg/kg (max 160 mg) by weekly SC injection and two 3-month courses of placebo (Arm B). Patients were randomized to 1 of 4 treatment sequences (ABAB, BABA, ABBA, BAAB). Escape visits were allowed to permit switching arms (blinding was maintained) for patients with at least 2 attacks within a course. The primary outcome was the difference of FMF attacks between rilonacept and placebo courses with responders defined as subjects with a >40% difference. Results were analyzed by paired t-and signed rank tests. Results Fourteen subjects were randomized, 8 males and 6 females, mean (±SD) age 24.4±11.8 years (range 4.547.3; 4 patients <18 years), disease duration 17.5±12.6 yrs, with a baseline of 3.1±2.0 attacks per month. Eleven completed the full study and 3 dropped out (1 due to lack of efficacy, 1 due to distance from study site and 1 lost to follow-up). Among 12 patients who completed at least 2 treatment courses the mean number of attacks per month on rilonacept was 1.0±1.2 vs. 1.8±0.9 on placebo (P=0.021 by paired t-test and 0.027 by signed rank test). There were 8 responders; all 4 non-responders were adults. There were 2 respiratory infection SAEs, 1 on rilonacept and 1 on placebo. Injections site reactions were significantly more frequent with rilonacept but no differences were seen in other adverse events, including infections.