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ObjectiveRecurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.MethodsThis multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).ResultsOutcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients. Secondary outcomes: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.ConclusionsRilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.Trial registration numberNCT03980522.

Introduction:Interleukin-1 (IL-1) mediates innate autoinflammation and is implicated in recurrent pericarditis (RP). We report final data from a Phase 2 study of rilonacept (IL-1?/IL-1? inhibitor) in RP.Methods:Symptomatic or corticosteroid (CS)-dependent asymptomatic pts with idiopathic or post-pericardiotomy RP received open-label rilonacept (320mg SC load; 160mg SC weekly) during a 6-wk treatment period (TP) and an optional 18-wk extension period (EP). Baseline NSAIDs, colchicine, and/or CS were continued during TP and weaned optionally during EP. Efficacy endpoints were change in pericardial pain (NRS) and CRP (symptomatic RP) and disease activity after CS taper (CS-dependent asymptomatic RP).Results:Of 25 adults with RP (21 idiopathic, 4 post-pericardiotomy, mean age 42.8 y, mean 2.6 prior recurrences, 20/25 pts on >2 pericarditis medications), 23 completed 6 months of rilonacept treatment. One pt chose not to continue into EP, and 1 discontinued TP due to a serious adverse event (SAE). In symptomatic RP pts with CRP >1mg/dL, lower pain and CRP levels were observed after the first injection and maintained to the end of study (Fig 1). Improvement/resolution of other pericarditis manifestations (pericardial effusion, ECG changes, pericardial rub) and improvements in global physical and mental health scores were observed. No subject had pericarditis recurrence in EP, and of 12 pts on CS at baseline completing EP, 1 reduced CS dose and 10 stopped CS during EP. Two SAEs were reported: skin abscess resulting in rilonacept discontinuation and atypical chest pain; both resolved. Most common adverse events were injection site reactions, all mild and none resulting in rilonacept discontinuation.Conclusions:Patient-reported and clinical measures of RP improved after first rilonacept injection. CSs were dose-reduced or discontinued. Observed AEs were consistent with known rilonacept safety profile. RHAPSODY, a Phase 3 trial, is enrolling.