Long-term treatment with nintedanib and pirfenidone in idiopathic pulmonary fibrosis: a comparative, real-world cohort study

Rationale: Limited data exists on the long-term comparative efficacy and tolerability of pirfenidone and nintedanib, the two approved treatments for idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively enrolled IPF patients treated with either pirfenidone or nintedanib at our centre between 2017 and 2023. Progression-free survival (PFS), defined as time to death or ≥ 10% decline in % predicted forced vital capacity (FVC) and continuous FVC decline were compared between groups defined by antifibrotic type or treatment intensity (full or reduced). Time to drug dose reduction was also compared. Statistical analysis included Kaplan-Meier curves with Log-Rank tests, Cox proportional hazards models and linear mixed-effects models. Results: A total of 292 IPF patients treated with pirfenidone (n = 142) or nintedanib (n = 150) were included with a mean follow-up time of 32.3 months (SD = 14.5). No significant differences in efficacy were observed between groups by antifibrotic type. Dose reduction was more frequent in the nintedanib group (59.3%) than pirfenidone group (16.9%, p < 0.001). Multivariate analysis showed that patients on nintedanib had a 4-fold higher risk of dose reduction compared to those on pirfenidone (p < 0.001). There were no significant differences in clinical outcomes between patients with dose reduction and those maintaining the full dose, both in the overall population and when stratified by antifibrotic type. Conclusion: Nintedanib and pirfenidone exhibited similar long-term efficacy. Dose adjustment was more frequent with nintedanib, however it did not have impact on clinical outcomes.