1664: Cardiac Sarcoidosis Response to Steroid-Sparing Immunosuppression

Background/Purpose: There are no FDA-approved therapies for cardiac sarcoidosis (CS), a disease associated with high morbidity and mortality. Treatment typically consists of glucocorticoids and off-label use of steroid-sparing immunosuppressive therapies. For over a decade, we have implemented a consistent treatment approach for patients with CS at our institution. Here we report the treatment outcomes of this approach and explore disease-related characteristics associated with first-line treatment failure.

Methods: This retrospective cohort study was conducted utilizing a registry of adult cardiac sarcoidosis patients seen in the Stanford University Cardiology and Rheumatology clinics between 1/1/2011 and 12/31/2024. All patients met the Heart Rhythm Society diagnostic criteria for CS or the Japanese Circulation Society criteria for isolated CS and were treated with a standard protocol (Figure 1), consisting of prednisone (20mg-60mg daily) and methotrexate (up to 25mg weekly), followed by the addition of a tumor necrosis factor (TNF) inhibitor for patients who did not have complete resolution of ¹⁸F-fluorodeoxyglucose (FDG) uptake on cardiac FDG-positron emission tomography/computed tomography (FDG-PET/CT) on methotrexate alone. Patients were excluded if they did not have at least one follow-up cardiac FDG-PET/CT after treatment initiation. Through manual chart review, we extracted demographics and clinical variables and determined treatment response. Comparisons between methotrexate responders and non-responders were made using Fisher’s exact test.

Results: Fifty-seven CS patients were followed for a mean (standard deviation [SD]) of 3.8 (3.0) years. After stopping prednisone, 18 patients (31.6%) on methotrexate monotherapy had complete resolution of FDG uptake on cardiac FDG-PET/CT, and 39 patients (68.4%) had ongoing disease activity. Methotrexate responders were older (66 years vs 62 years), more likely to be female (44% vs 26%), had fewer organs involved by their sarcoidosis (2.2 vs 2.9), and had a lower baseline left ventricular ejection fraction (40% vs 48%) (Table 1). Right ventricular involvement was present in only 1 of 18 (5%) methotrexate responders vs 13 of 39 (33%) methotrexate non-responders (p = 0.037). Of the methotrexate non-responders, 37 (95%) were treated with a TNF inhibitor, and all but one patient had a complete response to therapy (Table 2).

Conclusion: Treating cardiac sarcoidosis with upfront initiation of methotrexate and a relatively rapid prednisone taper over 28 weeks resulted in complete resolution of FDG uptake in roughly one-third of patients, with two-thirds requiring the addition of a TNF inhibitor; RV involvement was associated with more difficult to treat disease. Our results support the use of methotrexate as a first-line steroid-sparing medication for the treatment of CS, demonstrate the efficacy of TNF inhibitors in methotrexate non-responders, and highlight the need for future studies to further define risk factors for inadequate response to methotrexate.