Nintedanib in progressive fibrosing hypersensitivity pneumonitis: Real-world effects on lung function and survival

BackgroundFibrotic hypersensitivity pneumonitis (f-HP) may progress despite antigen avoidance and immunosuppressive therapy. Although nintedanib is approved for progressive pulmonary fibrosis (PPF), real-world evidence regarding its effectiveness and safety in f-HP, particularly when combined with immunosuppression, remains limited.ObjectivesTo compare lung function trajectories, survival, and treatment safety in patients with progressive f-HP treated with nintedanib plus immunosuppressive therapy versus immunosuppressive therapy alone.DesignRetrospective, single-center cohort study with a historical control group.MethodsPatients with a multidisciplinary diagnosis of f-HP who fulfilled the INBUILD criteria for PPF were included. Patients treated with nintedanib were compared with patients managed with immunosuppressive therapy alone. Longitudinal changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) over 24 months were analysed using linear mixed-effects models. Survival was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards regression.ResultsA total of 106 patients were included, of whom 54 received nintedanib and 52 received immunosuppressive therapy alone. Baseline characteristics were broadly comparable between groups. No statistically significant differences were observed in FVC or DLCO trajectories over 24 months, although a modest numerical trend towards relative FVC stabilisation was observed in the nintedanib group. Median survival from disease progression was longer in nintedanib-treated patients than in those not receiving antifibrotic therapy (178 vs 78 months; log-rank p = 0.001). In multivariable analysis, nintedanib use remained independently associated with improved survival (p = 0.013). Gastrointestinal adverse events were more frequent with nintedanib but were generally mild to moderate, and treatment discontinuation due to intolerance occurred in 7.4% of patients.ConclusionIn this real-world cohort of patients with progressive f-HP, nintedanib treatment was associated with longer survival despite similar lung function trajectories compared with immunosuppressive therapy alone, and had a manageable safety profile. Given the retrospective design and use of historical controls, the observed survival association should be interpreted cautiously and requires confirmation in prospective studies.