Real-world outcomes in PPF treated with nintedanib: a nationwide cohort study

Background Randomised trials have shown that nintedanib slows decline in lung function in progressive pulmonary fibrosis (PPF), but real-world outcomes remain limited. We evaluated long-term lung function trajectories, survival, and predictors of survival in a nationwide cohort initiating nintedanib. Methods This nationwide retrospective cohort study included all patients initiating nintedanib for PPF at the four tertiary Danish interstitial lung disease (ILD) centres between 2022 and 2024. Longitudinal changes in forced vital capacity (FVC) before and after treatment initiation were analysed using linear mixed-effects models. Survival was estimated using Kaplan-Meier analysis and Cox proportional hazards were used to identify predictors of mortality Results We included 359 patients (median age 72 years; 58% male). Median baseline FVC was 2.31 L (69% predicted) and diffusing capacity for carbon monoxide (D LCO ) 42% predicted. A usual interstitial pneumonia (UIP) pattern was present in 45%. The most frequent diagnoses were systemic autoimmune rheumatic disease-associated ILD (38%) and fibrotic hypersensitivity pneumonitis (28%). FVC decline decreased from 224 mL/year (95% CI 198–250) before treatment to 92 mL/year (95% CI 49–135) after initiation, a difference of 132 mL/year (95% CI 80–184; p<0.001). During a median follow-up of 25.2 months, 115 deaths occurred. Survival was 94.1% at 6 months, 84.8% at 12 months, and 70.7% at 24 months. Higher age and lower baseline FVC and DLCO were associated with increased mortality. Conclusion In this nationwide real-world PPF cohort, nintedanib was associated with reduced lung function decline, but mortality remained substantial, highlighting the aggressive nature of PPF.