Leveraging Interleukin-1 Blockade as a Therapeutic Strategy for Cardiac Sarcoidosis: Rationale and Design for the...

Cardiac sarcoidosis (CS) is an inflammatory condition characterized by granuloma formation that can lead to life-threatening arrhythmias and heart failure. Although corticosteroids have long been the mainstay of treatment, their use is associated with cumulative dose-limiting toxicities that can exacerbate cardiovascular risk, including hypertension, diabetes, and weight gain. Given the central role of the proinflammatory cytokine interleukin-1 (IL-1) in the pathophysiology of sarcoidosis, IL-1 blockade represents a promising and more targeted therapeutic avenue. This review aims to reassess current management strategies for CS and provide a detailed overview of the ongoing randomized, open-label, RandomizEd PhAse II TrIal of Rilonacept in Subjects With Cardiac Sarcoidosis (REPAIR-CS) (NCT06660732), which is investigating the efficacy of rilonacept, an IL-1α and IL-1β cytokine trap, added to standard nonbiologic therapy in patients with CS after 24 weeks of therapy. The study's design and endpoints, including the primary outcome of improvement in myocardial inflammation as measured by fluorodeoxyglucose-positron emission tomography imaging, will be discussed in the context of their potential to inform future treatment guidelines and improve outcomes for patients with this challenging disease.