Sarcoidosis is an inflammatory disease that can affect any organ system. Rarely, sarcoidosis can affect the heart, leading to life-threatening heart rhythm problems, heart failure, and death. There are no drugs specifically approved for the treatment of sarcoidosis. Remarkably, despite >50 years of use as the most common therapy for sarcoidosis, there is no proof that corticosteroid treatment works for cardiac sarcoidosis. Preliminary data indicate a role for interleukin-1, the prototypical cytokine, in granuloma formation in sarcoidosis and we have shown evidence of IL-1 inflammasome formation in cardiac tissue of patients with cardiac sarcoidosis. Clinical trials have shown that IL-1 blockers can improve outcomes in ischemic heart disease and heart failure. Our research seeks to evaluate whether IL-1 blockade with the IL-1 receptor antagonist, anakinra, can safely modulate systemic inflammation in patients with active cardiac sarcoidosis. IL- 1 blockade is a novel therapeutic strategy that has not been tested in cardiac sarcoidosis. We have designed a double-blind randomized placebo-controlled clinical trial of anakinra, an IL-1 receptor blocker, given for 4 weeks in 28 patients with cardiac sarcoidosis. We will determine feasibility of recruitment and tolerability of treatment with anakinra in cardiac sarcoidosis patients and determine the effects of anakinra on systemic inflammation as measured by C reactive protein and IL-6, inflammatory biomarkers shown to be surrogates for cardiovascular outcomes. The study will build on the collaboration of two CTSA hubs that are international leaders in cardiac sarcoidosis clinical care ? Virginia Commonwealth University and the University of Michigan, under the translational research leadership of Dr. Antonio Abbate, an expert in cardiac inflammation. This proposal addresses urgent unmet needs that are common to both the National Center for Advancing Translational Sciences (NCATS) and the American Heart Association (AHA) - defined as the need of translating biomedical discoveries into clinical applications to improve human health and specifically of developing therapies to attenuate disease impact of cardiac sarcoidosis ? a condition for which no targeted therapy exists. The results of this pilot study will serve as proof-of-concept data to conceive future phase III studies involving CTSA hubs across the country. A novel targeted treatment could bring about a much-needed paradigm shift in the treatment of cardiac sarcoidosis.
Cardiac sarcoidosis is a rare manifestation of sarcoidosis that can result in life-threatening arrhythmias and death, for which there are no specific therapies. Currently all forms of sarcoidosis, including cardiac sarcoidosis, are treated with the same approach that includes corticosteroids in approximately 60% of cases with a steroid- sparing agent in 30% of the cases, without any available guidance due to the lack of controlled clinical trials. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that appears to be involved in the exaggerated inflammatory response in sarcoidosis leading to granuloma formation. We propose a phase IIa study testing a novel targeted anti-inflammatory therapy inhibiting IL-1 in patients with cardiac sarcoidosis.