Comparative Outcomes and Side Effects of Immunosuppressants and Tumor Necrosis Factor Inhibitors in Sarcoidosis: A Real-World Data Analysis.

Abstract

Sarcoidosis is a complex systemic granulomatous disease with varying clinical manifestations, and immunosuppressive agents and tumor necrosis factor (TNF) inhibitors have been used in severe and refractory cases. However, the comparison of the serious side effects of these treatments remains poorly understood. In sarcoidosis, what is the 1-year risk of serious side effects among second-line agents (immunosuppressants) and TNF inhibitors? A retrospective analysis of data from the TriNetX Research Network, which includes de-identified medical records of patients with sarcoidosis treated with specific immunosuppressive agents or TNF inhibitors between 2012 and 2023 across 82 health care organizations. Propensity score matching (PSM) was used to mitigate confounding effects. A total of 13,814 patients receiving immunosuppressive agents were included. We found that patients who received mycophenolate mofetil (MMF) showed higher risks for inpatient hospitalization (hazard ratio [HR], 2.74; 95% CI, 2.11-3.56), critical care (HR, 2.37; 95% CI, 1.91-2.94), mechanical ventilation (HR, 4.04; 95% CI, 2.630-6.21), mortality (HR, 2.16; 95% CI, 1.70-2.75), and infections compared with those who received methotrexate. Azathioprine use showed increased risks for mortality, hematologic toxicity, and infections compared with methotrexate use. Among the 3,964 patients with sarcoidosis receiving TNF inhibitors, we found similar rare occurrence of serious side effects between infliximab and adalimumab, although a slightly higher risk of anemia (HR, 1.81; 95% CI, 1.22-2.67), thrombocytopenia (HR, 2.67; 95% CI, 1.75-4.07), and pneumonia (HR, 1.47; 95% CI, 1.02-2.10), but lower risk of skin soft tissue infection (HR, 0.39; 95% CI, 0.17-0.89) in the infliximab group. We used large real-world data with a PSM approach to demonstrate the heightened risk of infection and bone marrow suppression with MMF compared with the other immunosuppressants and a similar rate of serious side effects between infliximab and adalimumab.