Senior Medical Science Liaison Kiniksa Pharmaceuticals Denver, Colorado
Background: Corticosteroids (CSs) are often used long-term in patients with recurrent pericarditis (RP) who do not respond to NSAID or colchicine treatment. CSs are associated with substantial comorbidities. We report the CS-sparing effect of rilonacept (inhibitor of IL-1α/IL-1β, major cytokines mediating pericardial inflammation) in CS-treated and CS-dependent patients with RP of idiopathic or post-pericardiotomy syndrome (PPS) etiology.
Methods: Patients with RP of idiopathic or PPS etiology presenting with active pericarditis despite conventional therapy, including CS, or with CS-dependent non-active pericarditis, received rilonacept (320mg SC load; 160mg SC weekly) in an open-label Phase 2 study during a 6-week base treatment period (TP) on top of background NSAIDs, colchicine, and/or CS followed by an optional 18-week treatment extension period (EP) during which the conventional therapies were weaned at investigator’s discretion. Efficacy endpoints included change in pericardial pain numeric rating scale (NRS), C-reactive protein (CRP), and success in weaning from CS.
Results: Fifteen patients entered the study with ongoing CS (prednisone) treatment, with a median (range) duration of 4.4 (0.3-46.9) weeks and dose of 8 (1-50) mg/day at baseline (BL). Mean (SD) number of pericarditis episodes (index, recurrent, and qualifying, if applicable) was 4.1 (0.92); annualized incidence was 3.3 (2.4) episodes/year. All 13 patients who entered the EP either discontinued (11) or tapered (2) CS while on rilonacept with no pericarditis recurrences. Average pain NRS and CRP improved (active) or remained low (CS-dependent). No patients required re-initiation or increased dose of CS for pericarditis.
Conclusion: In this Phase 2 study, rilonacept treatment reduced pain and CRP and enabled tapering and discontinuation of CS in RP without inducing disease recurrence. This CS-sparing effect of rilonacept has the potential to decrease or even obviate CS use in RP and could represent an important therapeutic opportunity for targeted treatment of this serious and debilitating disease.