Interleukin-1 Blockade for Treatment of Cardiac Sarcoidosis

INCLUSION CRITERIA (all 3 criteria need to be met)

• Clinical diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society or the New Japanese Cardiac Sarcoidosis Guidelines (must meet one of the diagnostic pathways)
• Heart Rhythm Society Diagnostic Criteria based on 2 diagnostic pathways:
• Histological diagnosis from myocardial tissue - cardiac sarcoidosis is diagnosed in the presence of non-caseating granuloma on histologic examination of myocardial tissue with no alternative cause identified (including negative stain for microorganisms - as applicable);
• Clinical diagnosis from invasive and/or non-invasive studies - it is probable that there is cardiac sarcoidosis if there is (a) histological diagnosis of extracardiac sarcoidosis and (b) one or more of the following: steroid +/- immunosuppressant responsive cardiomyopathy or heart block; unexplained reduction in LVEF ( 3.5 in BAL fluid. 11.
• Diagnostic guidelines for isolated cardiac sarcoidosis based on New CS Guidelines in Japan Prerequisite
• No clinical findings characteristic of sarcoidosis are observed in any organs other than the heart. (The patient should be examined in detail for respiratory, ophthalmic, and skin involvement of sarcoidosis. When the patient is symptomatic, other etiologies that can affect the corresponding organs must be ruled out.)
• 67Ga scintigraphy or 18F-FDG PET reveals no abnormal tracer accumulation in any organs other than the heart.
• A chest CT scan reveals no shadow along the lymphatic tracts in the lungs or no hilar and mediastinal lymphadenopathy (minor axis>10 mm).
• Histological diagnosis group Isolated cardiac sarcoidosis is diagnosed histologically when endomyocardial biopsy or surgical specimens demonstrate non-caseating epithelioid granulomas.
• Clinical diagnosis group Isolated cardiac sarcoidosis is diagnosed clinically when criterion (d) and at least 3 other major criteria (a)-(e) are satisfied. (Table 1)
• Cardiac fluoro-deoxyglucose uptake on recent PET (performed within the prior month).
• CRP high-sensitivty assay >2 mg/l.

EXCLUSION CRITERIA (any of the following criteria would result in exclusion)

• Age 1 month] oral corticosteroids at a dose of prednisone less than 0.5 mg/kg/day or methotrexate).
• Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent from complying with study instructions;
• Limited English Proficiency that in the opinion of the investigator may prevent from understanding the content of the informed consent form or safely completing the study procedures.
• Live vaccination within the prior month
• Neutropenia (defined as absolute neutrophil count < 1,500/ml or <1,000/ml if subject is African American)
• History of malignancy within the prior 5 years (with exception of basal cell skin cancer, carcinoma in-situ of the cervix or low risk prostate cancer after curative therapy)
• Participation in another concurrent intervention study within 30 day or treatment with an investigational drug within 5 half-lives prior to randomization
• Severe kidney disease (GFR <30 mL/min/1.73m2)
• Evidence of COVID-19 within the last 60 days or recent (21 days) exposure to close personal contact with COVID-19.
• [Chronic, moderate-to-severe kidney disease (GFR <60 mL/min/1.73m2) or acute kidney injury, or history of severe hypersensitivity reactions to gadolinium-based contrast agents] - For VCU Imaging Substudy