The IL-1 decoy receptor rilonacept could be a therapeutic alternative for patients with familial Mediterranean fever who are resistant to, or intolerant of, treatment with colchicine. In a randomized, double-blind, single-participant alternating treatment study, the median number of attacks per month during 3-month courses of rilonacept 2.2 mg/kg was 0.77, compared with 2.00 during 3-month courses of placebo (median difference −1.74, 95% CI −3.4 to −0.1) in the 12 patients who completed the study. The duration of attacks did not differ between courses of placebo and rilonacept, however, and injection site reactions were more frequent with rilonacept.