Ryan, J.J.

Abstract Background Recurrent pericarditis (RP) is an IL-1-mediated chronic autoinflammatory disease (1,2). The phase 3 trial RHAPSODY demonstrated that rilonacept (IL-1α and IL-1β cytokine trap), the first and only FDA-approved treatment for RP, was effective in treating RP not only as a third-line agent (3L; after corticosteroids) but also as a second-line agent (2L; instead of corticosteroids) and reduced recurrence risk as monotherapy (3). The REgiStry Of the NAtural history of recurreNt periCarditis in pEdiatric and adult patients (RESONANCE) has been collecting long-term combined prospective and retrospective data from US-based pericardial-disease-dedicated programs since 2020 (4). Purpose To assess the efficacy of rilonacept in RP in a real-world setting, extending the clinical trial findings of RHAPSODY. Methods Database cut-off (DCO) was 05 February 2025. Data on RP management were collected and analyzed from pts with ≥2 years of observation in RESONANCE. Disease duration at DCO was defined as time from RP diagnosis to either disease resolution (no disease flares while off all RP treatments for ≥6 months before DCO) or last follow-up (for pts with ongoing treatment at DCO). Pericarditis recurrences (investigator-assessed) were confirmed based on RP symptom data and/or objective findings. Annualized recurrence rates were calculated per RP treatment regimen as total pericarditis recurrences divided by total patient-years (PY) while receiving that treatment. Wilcoxon signed-rank test was utilized to analyze the significance in change of annualized recurrence rates before and after rilonacept initiation. Results At DCO, 81 pts had ≥2 years of follow-up data in RESONANCE; mean (SD) age was 51.0 (16.8) years; most (66.7%) were female; 84% had idiopathic etiology; median (Q1-Q3) disease duration was 3.1 (2.6-3.7) years; and median observation was 2.93 (2.54-3.38) years. Patient-year treatment exposures per treatment were: NSAIDS ± colchicine (n=79; 187.8 PY), corticosteroids (n=30; 61.1 PY), anakinra (n=1; 1.2 PY) and rilonacept (n=35; 72.8 PY). Of the 35 pts treated with rilonacept for any duration (median observation: 3.2 years; median time on rilonacept: 2.08 years), the most common reason for rilonacept initiation was chest pain/recurrence on prior treatment (n=28). The annualized recurrence rate while receiving rilonacept was significantly lower versus all combined prior lines of treatment (4.00 vs. 0.02 events per PY; p=0.002); this outcome was consistent across line of treatment for rilonacept use (2L: 3.73 vs. 0.06 events per PY, p=0.02; 3L: 4.14 vs. 0 events per PY, p<0.001; Table 1). Conclusions This first report of real-world outcomes from RESONANCE shows that rilonacept-containing regimens for RP as 1st, 2nd, or 3rd line therapy reduced recurrence risk over long- term (>2 year) treatment, supporting prolonged management during RP natural history.