Rilonacept as monotherapy for long-term recurrent pericarditis management: sustained disease control over three years

Abstract Background Recurrent pericarditis (RP) predominantly shows features consistent with IL-1-mediated chronic autoinflammatory disease (1-4). A recent analysis suggested that supplementing anakinra with colchicine incrementally reduced pericarditis recurrence vs. anakinra alone (5). Rilonacept (a weekly IL-1α and IL-1β cytokine trap with 6-week washout) prevents engagement with IL-1 receptor, inhibiting both IL-1α and IL-1β activity (6). The Phase 3 trial RHAPSODY demonstrated rilonacept efficacy in two independent analyses: Randomized Withdrawal (RW) and Long-Term Extension (LTE) periods (7,8). Purpose Assess long-term recurrence-free persistence with rilonacept as monotherapy in pts with RP during the combined RW and LTE periods of RHAPSODY. Methods Post-hoc analysis. Freedom from recurrence on rilonacept monotherapy was quantified using the Kaplan-Meier (KM) method from RW start (if randomized to rilonacept) or from initiation of bailout rilonacept (if randomized to placebo) until the end of treatment. Prespecified recurrence adjudication criteria were pericarditis pain (numerical rating scale NRS) ≥4 plus C-reactive protein (CRP) ≥1 mg/dL. Per RHAPSODY protocol, background therapies were discontinued during the Run-In Period before randomization. In pts treated with rilonacept, concomitant colchicine was not added during the RW period. In the LTE, 6.8% (5/74) of pts added colchicine: one for 2 days of chest pain without CRP elevation, 4 in the absence of chest pain, CRP elevation, or recurrence; these 5 pts were censored in the KM curve at 6 days after last rilonacept dose or at colchicine initiation (whichever was first). One additional pt added colchicine prophylactically before an intentional rilonacept treatment interruption for elective cardiac surgery and experienced a recurrence after this interruption; this pt was not censored from the recurrence-free persistence analysis at colchicine initiation in order to capture this event. Results 74 pts (mean SD age 43.9 15.7 years, 83.8% idiopathic pericarditis, mean SD disease duration 2.5 3.2 years) were analyzed over three years. Rilonacept was well tolerated. Recurrence-free persistence was 95.9% (n=71/74) while receiving rilonacept as monotherapy (Figure 1). The three observed adjudicated recurrences were each associated with temporary interruptions of 1-3 doses of rilonacept. Conclusions Rilonacept as monotherapy provided recurrence-free persistence over the three-year trial duration when used continuously without interruption; pericarditis recurrences occurred only after interruptions. These findings support evidence-based use of rilonacept as monotherapy, minimizing the need for adjunctive treatments and reducing polypharmacy in long-term RP management. Further investigations are warranted to address how to assess pts as candidates for long-term treatment with rilonacept and when to cease rilonacept treatment.