Rilonacept and Other Interleukin-1 Inhibitors in the Treatment of Recurrent Pericarditis

Pericarditis is the commonest form of pericardial disease. Unfortunately, despite optimal treatment, approximately 15-30% of patients with acute pericarditis have recurrence. Many of these patients are refractory to colchicine, and become corticosteroid-dependent. Recurrent pericarditis severely impairs quality of life, and is associated with significant morbidity. Inflammasome formation and overproduction of interleukin (IL)-1 have been found to drive the systemic inflammatory response in recurrent autoinflammatory pericarditis. Several IL-1 inhibitors have been evaluated for their usefulness as therapeutic options. Rilonacept is a dimeric fusion protein that functions as a soluble decoy receptor that binds to both IL-1α and IL-1β, thereby inhibiting the IL-1 pathway. It is safe and efficacious in the treatment of recurrent pericarditis in the RHAPSODY II and III trials. Anakinra is a recombinant IL-1 receptor antagonist that blocks the action of circulating IL-1α and IL-1β. It has also been shown to be safe and efficacious in the AIRTRIP and IRAP studies. Canakinumab is a selective human monoclonal antibody against IL-1β, and data on its use in recurrent pericarditis is scarce. Several questions regarding IL-1 inhibitor therapy, such as the duration of treatment and the recommended tapering protocols, as well as their use in special populations like pregnant or lactating women, remain unanswered and need to be addressed in future studies.