Increased adoption of IL-1 pathway inhibition and the steroid-sparing paradigm shift: temporal trends in recurrent pericarditis treatment from the RESONANCE patient registry

Abstract Background Recurrent pericarditis (RP) is a chronic autoinflammatory disease mediated by IL-1 that requires long-term treatment. While the 2015 European Society of Cardiology Guidelines position IL-1 pathway inhibition only after corticosteroids, complications associated with long-term steroid use underscore the importance of steroid-sparing strategies. Rilonacept, an IL-1α and IL-1β cytokine trap, is the only FDA-approved treatment for RP (available since April 2021). RESONANCE, an ongoing 5-year non-interventional US registry of patients (pts) with RP, has collected real-world data from pts cared for by cardiologists with a focus on pericardial disease, with a goal of informing contemporary RP clinical management. Purpose Analysis of temporal trends in RP management from RESONANCE. Methods From a database cut-off (DCO) on 21 December 2023, patient demographics and disease characteristics are reported for 242 active RP pts (excluding RHAPSODY prior participants) at 20 US sites (median [Q1:Q3] 2.1 [1.5:2.6] years and 556 patient-years [PY] of observation). Complete medication class use data were available for 239 pts (total 546 PY). Proportional medication class use prior to initiating rilonacept was analyzed annually across the observation period. Results Mean (standard deviation) age at DCO was 50.2 (16.6) years; 58.1% were female. Median [Q1:Q3] disease duration at DCO from index pericarditis episode was 3.1 [2.2:5] years. Median [Q1:Q3] number of prior recurrences at enrollment was 3 [2:5]. Prior to rilonacept availability, NSAIDs/Colchicine/Aspirin represented the highest proportion of treatment (73% of PY); steroid use was 9% of PY, IL-1 pathway inhibition (anakinra) was 13% of PY, and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) were 0.46% PY (no RP-specific treatment was 5% of PY) (Fig 1). In the years since rilonacept availability, proportional IL-1 pathway inhibition use has increased, from 13% of PY in 2020-21 to 26% of PY in 2023, driven by an increase in rilonacept use (6%, 13%, 16% of PY in 2021, 2022, and 2023, respectively). Over that same period, proportional NSAIDs/Colchicine/Aspirin use (57%-63% of PY) has been consistently 6-times more than proportional steroid use (10%-11% of PY). Among pts who initiated rilonacept (n=81), similar proportions transitioned from NSAIDs/Colchicine/Aspirin as from corticosteroids (Fig 2), a robust trend observed each year. Of those pts transitioning from corticosteroids, 1/3 had used corticosteroids for <30 days and 1/3 for >6 months. Conclusions Real-world data from the RESONANCE registry reveal a temporal shift in RP management in US centers with RP-focused cardiologists, with increased proportional IL-1 pathway inhibition use since rilonacept availability in 2021. Advancing beyond 2015 guideline recommendations, IL-1 pathway inhibition is often being used as steroid-sparing treatment, i.e., after colchicine instead of chronic corticosteroids.