Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis

This phase 3 randomized-withdrawal trial (RHAPSODY) evaluated rilonacept, an interleukin-1α and interleukin-1β cytokine trap, in patients with recurrent pericarditis marked by systemic inflammation (CRP ≥1 mg/dL) and acute symptoms (pain score ≥4/10). In the 12-week open-label run-in phase, patients received weekly subcutaneous rilonacept, with rapid symptom resolution (median pain response: 5 days; CRP normalization: 7 days) and weaning from background medications. Sixty-one responders were randomized to continued rilonacept or placebo. Over a median follow-up of 8.6 weeks, recurrence occurred in 2 of 30 rilonacept recipients (7%) vs. 23 of 31 placebo recipients (74%) (HR 0.04; 95% CI: 0.01–0.18; P<0.001). Major secondary endpoints persistent clinical response at week 16, days with minimal pain, and symptom severity also favored rilonacept. Most adverse events were mild/moderate; injection-site reactions and upper respiratory infections were the most common. Lipid levels were modestly elevated but clinically manageable. The trial concludes that rilonacept provides rapid and sustained remission and substantially lowers recurrence risk in inflammatory recurrent pericarditis.

This phase 3 randomized-withdrawal trial (RHAPSODY) evaluated rilonacept, an interleukin-1α and interleukin-1β cytokine trap, in patients with recurrent pericarditis marked by systemic inflammation (CRP ≥1 mg/dL) and acute symptoms (pain score ≥4/10). In the 12-week open-label run-in phase, patients received weekly subcutaneous rilonacept, with rapid symptom resolution (median pain response: 5 days; CRP normalization: 7 days) and weaning from background medications. Sixty-one responders were randomized to continued rilonacept or placebo. Over a median follow-up of 8.6 weeks, recurrence occurred in 2 of 30 rilonacept recipients (7%) vs. 23 of 31 placebo recipients (74%) (HR 0.04; 95% CI: 0.01–0.18; P<0.001). Major secondary endpoints persistent clinical response at week 16, days with minimal pain, and symptom severity also favored rilonacept. Most adverse events were mild/moderate; injection-site reactions and upper respiratory infections were the most common. Lipid levels were modestly elevated but clinically manageable. The trial concludes that rilonacept provides rapid and sustained remission and substantially lowers recurrence risk in inflammatory recurrent pericarditis.