Luis, S A

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.

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.

Abstract Background Nearly 40,000 people in the U.S. experience recurrent pericarditis with up to 90% of cases having no identifiable cause, often making the journey to diagnosis arduous. Understanding the challenges that patients and health care professionals (HCP) face will help address gaps and barriers in patient diagnosis and care. In addition, the lack of U.S. based guidelines for recurrent pericarditis clinical care, coupled with the time lapse from the last published European guideline, has created an opportunity to discover workflow solutions for U.S. based healthcare professionals. Purpose The American Heart Association’s (AHA) Addressing Recurrent Pericarditis Initiative is a three-year effort utilizing a quality improvement approach to address gaps/barriers in patient care, educate HCPs, and develop patient education resources to improve diagnosis, treatment, and quality of life. To accomplish this, the lived experiences and challenges patients face on their journey to diagnosis was integrated into the qualitative research process. Methods To assess quality improvement opportunities, the AHA engaged HCPs with recurrent pericarditis experience from 15 diverse health systems to participate in a learning collaborative strategy for quality improvement and implementation to share successful strategies, provide input on professional education topics, and participate in process mapping. Data collection strategies include 1:1 consultations, quarterly learning collaborative calls, surveys and questionnaire completion. To assess patient education needs, the AHA Market Research Team held 1-hour video interviews with ten diverse patients. Results AHA-led HCP interviews produced process maps of clinical workflows and identified opportunities for standardization to improve clinical workflow and patient outcomes (Figure 1). From these data collection methods, preliminary results include care coordination across clinical settings, exploring treatment options, standardization of follow-up cadence, and provider awareness of misdiagnoses/underdiagnosis rates. The patient interviews revealed that there is a lack of symptom recognition, persistent rate of misdiagnosis, delay in accurate diagnosis and treatment, and discrepancies in diagnosis and treatment for various demographics including female and younger adult patients (Figure 2). Conclusion(s) In Year 2 of this three-year initiative, we will continue to refine identified areas of opportunities to improve patient outcomes by creating and disseminating educational materials and launch awareness campaigns, while also producing a national education series for HCPs that provide guidance for system-level quality improvement to emphasize consistency in care and reductions in health inequities. Key findings from this study highlight the care coordination involved in the treatment of patients with recurrent pericarditis and the need to provide multidiscipline educational approaches to achieve this goal.Figure. 1 Summary of care pathway Figure. 2 Summary of patient interviews