Transition to rilonacept monotherapy from oral therapies in patients with recurrent pericarditis

Objective: Polypharmacy management of recurrent pericarditis (RP) often involves long-term therapies, often with negative effects. Slow tapering of oral therapies is often required to avoid recurrence. A post hoc analysis of the phase III trial Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes Study (RHAPSODY) evaluated investigator approaches to transitioning to IL-1 blockade monotherapy with rilonacept, which was hypothesised to allow accelerated withdrawal of common multidrug pericarditis regimens.

Methods: RHAPSODY was a multicentre (Australia, Israel, Italy, USA), double-blind, placebo-controlled, randomised-withdrawal trial in adults and adolescents with RP. Investigators initiated rilonacept at the labelled dose level and discontinued oral pericarditis therapies during the 12-week run-in; randomised patients received study drug as monotherapy. Time to rilonacept monotherapy was quantified in patients receiving multidrug regimens at baseline who achieved rilonacept monotherapy during run-in.

Results: In 86 enrolled patients, mean time to rilonacept monotherapy was 7.9 weeks, with no recurrences. Of these, 64% (n=55) entered on multidrug regimens: non-steroidal anti-inflammatory drugs (NSAIDs) plus colchicine (44% (24/55)), colchicine plus glucocorticoids (24% (13/55)), or NSAIDs, colchicine, plus glucocorticoids (33% (18/55)). Investigators transitioned patients receiving colchicine and glucocorticoids at baseline to rilonacept monotherapy without recurrence regardless of taper approach: sequential (n=14; median, 7.7 weeks) or concurrent (n=17; median, 8.0 weeks). Median time to rilonacept monotherapy was similar regardless of glucocorticoid dose and duration: ≤15 mg/day (n=21): 7.3 weeks; >15 mg/day (n=18): 8.0 weeks; long-term (≥28 days): 7.6 weeks.

Conclusions: Rapid discontinuation of oral RP therapies while transitioning to rilonacept monotherapy was feasible without triggering pericarditis recurrence.

Trial registration number: NCT03737110.