To assess the efficacy and safety of rilonacept (Interleukin‐1 [IL‐1] Trap), a long‐acting and potent inhibitor of IL‐1, in patients with cryopyrin‐associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS) and Muckle‐Wells syndrome (MWS).

Forty‐seven adult patients with CAPS, as defined by mutations in the causative NLRP3 (CIAS1) gene and pathognomonic symptoms, were enrolled in 2 consecutive phase III studies. Study 1 involved a 6‐week randomized double‐blind comparison of weekly subcutaneous injections of rilonacept (160 mg) versus placebo. Study 2 consisted of 9 weeks of single‐blind treatment with rilonacept (part A), followed by a 9‐week, randomized, double‐blind, placebo‐controlled withdrawal procedure (part B). Primary efficacy was evaluated using a validated composite key symptom score.

Forty‐four patients completed both studies. In study 1, rilonacept therapy reduced the group mean composite symptom score by 84%, compared with 13% with placebo therapy (primary end point; P < 0.0001 versus placebo). Rilonacept also significantly improved all other efficacy end points in study 1 (numbers of multisymptom and single‐symptom disease flare days, single‐symptom scores, physician's and patient's global assessments of disease activity, limitations in daily activities, and C‐reactive protein and serum amyloid A [SAA] levels). In study 2 part B, rilonacept was superior to placebo for maintaining the improvements seen with rilonacept therapy, as shown by all efficacy parameters (primary end point; P < 0.0001 versus placebo). Rilonacept was generally well tolerated; the most common adverse events were injection site reactions.

Treatment with weekly rilonacept provided marked and lasting improvement in the clinical signs and symptoms of CAPS, and normalized the levels of SAA from those associated with risk of developing amyloidosis. Rilonacept exhibited a generally favorable safety and tolerability profile.