Effectiveness of antifibrotic treatment in real-world patients with progressive pulmonary fibrosis

PURPOSE: The suitability of progressive pulmonary fibrosis (PPF) as a criterion for antifibrotic use remains uncertain. We aimed to evaluate the effectiveness of antifibrotics for patients with different criteria of progressive non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD). MATERIAL AND METHODS: In this multicenter, retrospective cohort study, we estimated the effect of antifibrotic drugs in three cohorts of PF-ILD (progression within 24 months under standard non-antifibrotic therapy, as in the INBUILD trial), PPF (progression within 12 months based on ATS/ERS/JRS/ALAT guidelines), and PPF "despite management" (a subset of PPF with progression despite appropriate non-antifibrotic therapy). Analyses used the parametric G-formula, the time-varying Cox hazard model, and inverse probability weighting (IPW). RESULTS: Among 1754 patients with non-IPF ILD, 327, 567, and 326 patients were diagnosed with PF-ILD (134 antifibrotics, 193 non-antifibrotics), PPF (149 antifibrotics, 418 non-antifibrotics), and PPF "despite management" (115 antifibrotics, 211 non-antifibrotics), respectively. Using the parametric G-formula, antifibrotic therapy was associated with higher estimated survival in PF-ILD, with statistically significant differences during the first three years, and with a consistent survival advantage in the PPF "despite management" cohort. In contrast, no clear survival benefit was observed in the PPF cohort. These findings were consistent with the time-varying Cox hazard model and IPW analysis results. CONCLUSION: Our results demonstrate antifibrotic therapy was associated with higher estimated survival in patients with PF-ILD in a real-world setting, suggesting the importance of including "despite management" as a criterion for antifibrotic therapy eligibility in the PPF diagnosis.