BACKGROUND: Interleukin-1 has been implicated as a mediator of recurrent 
pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and 
interleukin-1β cytokine trap, were studied previously in a phase 2 trial 
involving patients with recurrent pericarditis.
METHODS: We conducted a phase 3 multicenter, double-blind, event-driven, 
randomized-withdrawal trial of rilonacept in patients with acute symptoms of 
recurrent pericarditis (as assessed on a patient-reported scale) and systemic 
inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients 
presenting with pericarditis recurrence while receiving standard therapy were 
enrolled in a 12-week run-in period, during which rilonacept was initiated and 
background medications were discontinued. Patients who had a clinical response 
(i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio 
to receive continued rilonacept monotherapy or placebo, administered 
subcutaneously once weekly. The primary efficacy end point, assessed with a Cox 
proportional-hazards model, was the time to the first pericarditis recurrence. 
Safety was also assessed.
RESULTS: A total of 86 patients with pericarditis pain and an elevated CRP level 
were enrolled in the run-in period. During the run-in period, the median time to 
resolution or near-resolution of pain was 5 days, and the median time to 
normalization of the CRP level was 7 days. A total of 61 patients underwent 
randomization. During the randomized-withdrawal period, there were too few 
recurrence events in the rilonacept group to allow for the median time to the 
first adjudicated recurrence to be calculated; the median time to the first 
adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence 
interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 
0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 
of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as 
compared with 23 of 31 patients (74%) in the placebo group. In the run-in 
period, 4 patients had adverse events leading to the discontinuation of 
rilonacept therapy. The most common adverse events with rilonacept were 
injection-site reactions and upper respiratory tract infections.
CONCLUSIONS: Among patients with recurrent pericarditis, rilonacept led to rapid 
resolution of recurrent pericarditis episodes and to a significantly lower risk 
of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; 
RHAPSODY ClinicalTrials.gov number, NCT03737110.).