Earlier rilonacept use in recurrent pericarditis reduces subsequent recurrence burden and treatment escalation: outcomes from the RESONANCE patient registry

Background Recurrent pericarditis (RP) is an IL-1-mediated chronic autoinflammatory disease. In the Phase 3 trial RHAPSODY, rilonacept (IL-1α and IL-1β cytokine trap) treated RP and reduced recurrence risk not only in third-line (3L; after glucocorticoids [GC]) but also in second-line (2L; instead of GC) use. The multi-center REgiStry Of the NAtural history of recurreNt periCarditis in pEdiatric and adult patients (RESONANCE) showed that 2L treatment choice in the US shifted from GC to IL-1 pathway inhibition in the first 3 years after rilonacept availability in RP as the first and only FDA-approved treatment for RP, agnostic to line of therapy. Hypothesis: Rilonacept initiation earlier in the RP disease course reduces recurrence burden and escalation to next line therapy versus conventional (first-line [1L] or 2L) therapies (NSAIDs/colchicine and/or GC). Methods In patients with ≥2 years observation at data cut off (DCO; 15-Jan-26), disease duration was defined as time from RP diagnosis to last follow-up (ongoing disease) or to disease resolution (no flares while off all RP therapy ≥6 months). Investigator-assessed pericarditis recurrences were adjudicated based on available objective data, and annualized recurrence rates (ARR/PY) were calculated. Changes in ARR were modeled using generalized estimating equations with a negative binomial regression. Results At DCO, 261 pts were analyzed (86% idiopathic; median disease duration 5.3 yrs; median observation 3.5 yrs). Of the pts initiating 1L NSAIDs ± colchicine (n=255), 32.5% (n=83) remained on NSAIDs ± colchicine (of whom 68.7% [n=57] increased NSAIDs/ colchicine dose); 67.5% (n=172) advanced to 2L therapy (IL-1 pathway inhibition [44.2%; n=76]; GC [55.8%; n=96]). 2L rilonacept significantly reduced ARR versus prior NSAIDs ± colchicine (0.014 vs 1.03; 98.6% reduction; P<0.001), whereas 2L GC significantly increased ARR versus prior NSAIDs ± colchicine (2.04 vs 1.21; 68.6% increase; P<0.001; Table 1). Pts initiating 1L rilonacept (n=6) accrued no recurrences over 1.7 years, whereas pts initiating 1L NSAIDS ± colchicine (n=255) had ARR of 1.03. Rilonacept-treated pts had the lowest escalation rate to next line therapies (10.3% [6/58]), whereas 80.0% of pts on 1L NSAIDs ± colchicine (n=204/255) and 68.8% of pts on 2L GC (n=66/96) escalated to next line therapies. Conclusions In this multicenter US registry, rilonacept use earlier in the RP disease course (reflected in ACC Concise Guidance) reduced recurrence rates and need for next line therapy; conversely, 2L GC use (consistent with ESC Guidelines) increased recurrence rates and need for next line therapy. High rates of dose intensification, treatment escalation, and suboptimal disease control observed with 1L NSAIDs ± colchicine are also important considerations when evaluating IL-1 pathway inhibition use earlier in the disease course to minimize recurrence burden and streamline long-term disease management.