Clinical outcomes of subglottic stenosis in granulomatosis with polyangiitis: results of an international multicentre observational study

OBJECTIVES: Subglottic stenosis (SGS) is a challenging manifestation of granulomatosis with polyangiitis (GPA), often relapsing and poorly responsive to immunosuppressive treatment. Current guidelines lack specific recommendations for SGS management and evidence is limited. This study aimed to identify features of SGS associated with a more aggressive course and to assess the efficacy of available treatments in preventing relapses. METHODS: We conducted a multicentre, retrospective cohort study including GPA patients with SGS. Patients were stratified into higher relapsers (≥2 flares) and lower relapsers (≤1 flare). Clinical and treatment features were compared across groups. Univariate and multivariate analyses were conducted to identify independent predictors of relapse and multiple flares. Kaplan-Meier curves assessed time-to-relapse across regimens. RESULTS: Eighty-nine patients were included (30% male). Forty-eight patients (54%) were higher relapsers, with a median time-to-relapse of 36 months. Systemic immunosuppressive therapy was associated with fewer relapses (82% vs 18%, P = 0.04) compared with local treatments alone. Glucocorticoids in induction regimens reduced relapse risk (86% vs 12%, P = 0.03). Cyclophosphamide (CYC) was associated with the longest relapse-free survival and reduced 5-year relapse risk (HR 0.33, P = 0.049). By contrast, glucocorticoid monotherapy in either induction or maintenance phase was associated with higher relapse rate (P = 0.006). No specific maintenance regimen was significantly protective, though rituximab and DMARDs showed a trend toward improved outcomes. CONCLUSION: Systemic immunosuppressive therapy, particularly CYC-based induction, was associated with fewer SGS relapses and prolonged relapse-free survival, while glucocorticoid monotherapy was less effective. Prospective studies are needed to optimize induction and maintenance strategies in GPA-related SGS.