Comparative effectiveness of disease modifying antirheumatic drugs for patients with cardiac sarcoidosis

Objectives: We aimed to evaluate the comparative efficacy of disease modifying antirheumatic drugs (DMARDs) for patients with cardiac sarcoidosis.

Methods: We performed a retrospective cohort study of new users of methotrexate, mycophenolate, or azathioprine for sarcoidosis using the US-based TriNetX electronic health records database from 2008-2023. Hazard ratios were calculated using inverse probability of treatment weighted Cox proportional hazards regressions to compare the efficacy of DMARDs with respect to delaying major adverse cardiac events among patients with cardiac sarcoidosis and preventing cardiac sarcoidosis from developing among patients with non-cardiac sarcoidosis.

Results: Among 3,441 patients with sarcoidosis, 601 were defined as cardiac sarcoidosis and 2,840 as non-cardiac sarcoidosis. The average age of the cohort was 52.1 years (standard deviation 11.9 years) and the majority were female (55.9%) and white (50.0%). Among patients with cardiac sarcoidosis at baseline, the risk of serious cardiac outcomes was similar for patients who initiated therapy with mycophenolate mofetil (HR 0.83, 95% CI 0.43-1.59) or azathioprine (HR 0.74, 95% CI 0.29-1.89) as compared with methotrexate. Among patients who did not have cardiac sarcoidosis at baseline, the risk of developing cardiac sarcoidosis was similar for patients who initiated therapy with mycophenolate mofetil (HR 1.11, 95% CI 0.46-2.66) and azathioprine (HR 0.54, 95% CI 0.15-1.91) as compared with methotrexate. Mycophenolate mofetil (HR 1.83, 95% CI 1.10-3.05) and azathioprine (HR 1.32, 95% CI 0.92-1.89) increased risk of infection.

Conclusion: A strategy of methotrexate had a favorable safety profile in terms of infection risk and may be favored over azathioprine or mycophenolate mofetil for patients with sarcoidosis or cardiac sarcoidosis.