Immunosuppression and Surgery-Free Interval in Granulomatosis With Polyangiitis Airway Stenosis.

Abstract

Subglottic and tracheal stenosis (SGS, TS) are severe manifestations of granulomatosis with polyangiitis (GPA), often-requiring endoscopic airway intervention and systemic immunosuppression. Rituximab (RTX) has shown efficacy for systemic GPA, but its role in SGS and TS remains unclear, with reports of both benefit and relapse. This study evaluated the impact of RTX and cyclophosphamide (CTX) on surgery-free intervals (SFIs) in GPA-associated SGS and TS. A retrospective chart review was conducted on GPA patients with SGS or TS treated at a tertiary center between 1992 and 2023. Therapeutic RTX exposure was defined as 3-9 months post-induction or within 1 year of maintenance, and CTX during regular dosing before transitioning to another maintenance regimen. SFIs, calculated as time between endoscopic interventions, were compared with and without RTX and CTX exposure using weighted t-tests. A total of 55 patients met inclusion; 44 (80%) underwent at least one endoscopic intervention and 34 of those patients (77%) received RTX and/or CTX. Median follow-up time was 10.2 years (range 0.8-29.5 years). Mean SFIs were significantly longer during therapeutic RTX exposure or remission (45 ± 8 months) versus non-therapeutic intervals (20 ± 6 months) (p = 0.046). Prior RTX or CTX use, though not definitionally therapeutic, significantly increased mean SFI from 22 to 25 months compared to no exposure (p = 0.029). CTX alone did not significantly increase SFI. Rituximab may contribute to longer intervals between endoscopic airway intervention and delay relapse in GPA-related airway stenosis, supporting its role in stabilization of airway manifestations. Multidisciplinary management remains essential for this life-threatening GPA manifestation.