Medical Science Liaison Kiniksa Pharamceuticals Lexington, Massachusetts
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-1α/IL-1β 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. Confirmatory data are expected from RHAPSODY, a Phase 3 trial.