Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis

Project: CSA

Investigators

  • Jordana Kron (CoI)
  • Jennifer Hawthorne Jordan (CoI)
  • Antonio Abbate (CoI)
  • W Gregory Hundley (CoI)

Description

Sarcoidosis is a multisystem, granulomatous inflammatory disease seen worldwide, with a prevalence of 4.7 to 64 in 100,000. Based on autopsy studies, cardiac involvement can occur in up to 25% of patients with sarcoidosis in other organ systems. Cardiac sarcoidosis (CS) is an uncommon disease that can lead to ventricular arrhythmias, conduction abnormalities, heart failure, and death. Remarkably, despite >50 years of use as the most common therapy for sarcoidosis, there is no proof of survival benefit from corticosteroid treatment. There is also conflicting data on the efficacy of steroids on long-term disease outcomes.IL-1 is a proinflammatory cytokine that plays an important role in atherosclerosis, acute MI, and heart failure. IL-1 blockade has been evaluated as a potential therapeutic target. The recently published landmark CANTOS trial demonstrated in more than 10,000 patients with previous myocardial infarction and elevated high-sensitivity C-reactive protein, that canakinumab, a monoclonal antibody targeting interleukin-1 beta, led to significantly lower rates of cardiovascular events. Anakinra is a recombinant human IL-1 receptor antagonist that blocks IL-1alpha and IL-1beta and is used to treat rheumatoid arthritis, juvenile arthritis, and gouty arthritis and has a proven beneficial cardiovascular profile compared to the TNFalpha monoclonal blocking antibody infliximab (which increased CRP levels and worsened outcomes). Longitudinal monitoring of cardiac sarcoidosis with PET imaging is challenging and limited given the spatial resolution and risk of repeated exposure to ionizing radiation. Cardiovascular magnetic resonance (CMR) imaging is a non-invasive imaging methodology, does not expose patients to ionizing radiation, has high spatial and temporal resolution, and can identify inflammation and fibrosis in myocardial tissue using quantitative CMR techniques such as late gadolinium enhancement and T2 mapping. Combining expertise in cardiac sarcoidosis, biomedical engineering, inflammation, and clinical cardiovascular imaging research, our newly formed research team proposes to detect the inflammatory changes in cardiac sarcoidosis using CMR imaging in order to guide anti-inflammatory therapy. We also propose that targeted therapy with anakinra, an IL-1 receptor antagonist, can reduce myocardial inflammation in patients with cardiac sarcoidosis resulting in improved cardiac diastolic and systolic function and reduced arrhythmogenicity.
Award amount$750,000.00
Award date07/01/2019
Program typeCollaborative Sciences Award
Award ID19CSLOI34580004
Effective start/end date07/01/201906/30/2022
StatusActive