Methotrexate and Rituximab Use in Highly Recurrent Idiopathic Subglottic Stenosis

Objective To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(−). Methods This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated. Results A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre‐drug interval: 338; mean post‐drug interval: 697 days) (p‐value = 0.25). Three patients did not recur following drug initiation with median follow‐up of 1265 days. All three treatment groups demonstrated a trend toward increased post‐drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post‐drug recurrence intervals (mean pre‐drug interval: 341 days, mean post‐drug interval 978 days) (p‐value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%). Conclusion MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy. Level of Evidence 3 Laryngoscope, 135:168–175, 2025 Limited data exist on treatment options for highly recurrent idiopathic subglottic (iSGS) stenosis patients. Our article explores the usage of methotrexate and rituximab for this patient population. Although initial results are promising, more work is needed to delineate drug candidacy and effectiveness.