Effect of Systemic Immunomodulators on Incidence of Alopecia Areata: A Retrospective Cohort Study

ABSTRACT Background Alopecia areata (AA) is a chronic autoimmune hair loss disorder. Patients with primary autoimmune diseases commonly use systemic immunomodulators to manage disease and have an increased risk of developing AA. Systemic immunomodulators have diverse immunologic effects, but their impact on AA risk is not well understood. Objectives We aimed to evaluate the association between individual systemic immunomodulators and the subsequent development of AA in patients with primary autoimmune conditions. Methods We conducted a retrospective cohort study using the TriNetX global health network. Deidentified data from over 275 million patients from healthcare organizations were queried. Results Patients on leflunomide had an associated decreased relative risk of AA incidence (RR [95% CI] = 0.478 [0.233, 0.981]) compared to healthy controls. Methotrexate (2.192 [1.774, 2.708]), cyclosporine (3.598 [2.889, 4.480]), and rituximab (1.828 [1.162, 2.874]) were associated with increased AA risk. Other immunomodulators analyzed showed no significant difference from controls. Overall, DMARDs (1.668 [1.505, 1.848]) and TNF‐α inhibitors (1.662 [1.222, 2.26]) were associated with an increased AA incidence. Conclusions Patients on leflunomide have an associated decreased frequency of AA development, while other immunomodulators, such as methotrexate, cyclosporine, and rituximab, may increase AA risk when used for other primary autoimmune diseases.