Absence of Pericarditis Recurrence in Rilonacept-Treated Patients with COVID-19 and SARS-CoV-2 Vaccination: Results from RHAPSODY Long-Term Extension

Background Rilonacept inhibits the interleukin-1 pathway, and extended treatment in patients with recurrent pericarditis reduced recurrence risk by 98% in the Phase 3 trial RHAPSODY long-term extension (LTE). SARS-CoV-2 vaccination/infection may trigger pericarditis recurrence, and in clinical practice, it is unknown whether to continue rilonacept during SARS-CoV-2 infection. This post-hoc analysis of the RHAPSODY LTE aimed to inform rilonacept management in recurrent pericarditis patients vaccinated against SARS-CoV-2 or who contract COVID-19. Methods Analysis was conducted from May 2020 to June 2022. The LTE enabled up to 24 months of additional open-label rilonacept treatment beyond the pivotal study. Rilonacept efficacy data in preventing pericarditis recurrence were assessed, and concomitant SARS-CoV-2 vaccination and COVID-19 adverse event data were evaluated. Results No pericarditis recurrences were temporally associated with vaccination. Sixteen COVID-19 cases were reported; ten in 30 (33%) unvaccinated/partially vaccinated versus 6/44 (14%) fully vaccinated patients (P=0.04). Twelve of 16 (75%) patients were receiving rilonacept at the time of infection, and none experienced pericarditis recurrence. One pericarditis recurrence occurred in the peri-COVID-19 period in 1 of 4 patients who had stopped rilonacept treatment >4.5 months prior. COVID-19 severity was mild in 13 patients, moderate in 2, and severe in 1. Conclusions Full vaccination effectively reduced COVID-19 events in patients treated with rilonacept. Vaccination or COVID-19 during rilonacept treatment did not increase pericarditis recurrence. Continued rilonacept treatment in patients contracting COVID-19 did not worsen disease severity, while rilonacept interruption increased pericarditis recurrence, supporting a recommendation for continued rilonacept treatment for recurrent pericarditis during vaccination or COVID-19.