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.

Figure 1. Cardiac sarcoidosis treatment and monitoring approach.

Table 1. Demographics and baseline characteristics of cardiac sarcoidosis patients.

Table 2. Cardiac sarcoidosis treatment characteristics and outcomes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cardiac-sarcoidosis-response-to-steroid-sparing-immunosuppression/