Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART)

Jordana Kron, Thomas Crawford, Virginia Mihalick, Frank Bogun, Jennifer H Jordan, Todd Koelling, Huzaefah Syed, Aamer Syed, Thomas Iden, Kelly Polly, Emily Federmann, Kirsta Bray, Sangeeta Lathkar-Pradhan, Shilpa Jasti, Lynda Rosenfeld, David Birnie, Melissa Smallfield, Le Kang, Alpha Berry Fowler, Amy Ladd, Kenneth Ellenbogen, Benjamin Van Tassell, W Gregory Hundley, Antonio Abbate, Jordana Kron, Thomas Crawford, Virginia Mihalick, Frank Bogun, Jennifer H Jordan, Todd Koelling, Huzaefah Syed, Aamer Syed, Thomas Iden, Kelly Polly, Emily Federmann, Kirsta Bray, Sangeeta Lathkar-Pradhan, Shilpa Jasti, Lynda Rosenfeld, David Birnie, Melissa Smallfield, Le Kang, Alpha Berry Fowler, Amy Ladd, Kenneth Ellenbogen, Benjamin Van Tassell, W Gregory Hundley, Antonio Abbate

Abstract

Background: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis.

Methods: Building on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis.

Discussion: The current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities. Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.

Keywords: Cardiac sarcoidosis; Heart failure; Inflammation; Interleukin-1.

Conflict of interest statement

Dr. Abbate (AA) has served as consultant to Swedish Orphan Biovitrum in the past. Dr. Van Tassell (BVT) has served as consultant to Swedish Orphan Biovitrum in the past. No other authors have relevant disclosures.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Design of the Multimodality Assessment of Granulomas in Cardiac Sarcoidosis—Anakinra Randomized Trial (MAGiC-ART). The overall study design is represented as a schematic. Abbreviations: CMR, cardiac magnetic resonance; CRP, C-reactive protein; HRS, Heart Rhythm Society; PET, positron emission tomography; QoL, quality of life. Procedures shown in brackets are additional testing done as part of the VCU Imaging Sub-study

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