Antifibrotic therapy in patients with pleuroparenchymal fibroelastosis: a multicentric observational study

Abstract

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease characterized by upper-lobe predominant pleural and subpleural fibrosis and associated with poor prognosis. No evidence-based medical therapy is currently established, and lung transplantation remains the only potentially curative option for selected patients. Antifibrotic agents such as nintedanib and pirfenidone have demonstrated efficacy in other fibrosing interstitial lung diseases, but their role in PPFE remains uncertain. This study aimed to evaluate the clinical outcomes, including lung function decline, survival, and safety, associated with antifibrotic therapy in patients with PPFE in a multicenter setting. We conducted a retrospective multicenter observational study in five expert centers of the French OrphaLung network. Adult patients with a multidisciplinary diagnosis of definite or consistent PPFE were included. Clinical characteristics, imaging findings, lung function tests, treatments, and outcomes were collected from the Colibri database. Patients were categorized according to exposure to antifibrotic therapy (nintedanib or pirfenidone). The primary endpoint was the annualized change in forced vital capacity (FVC). Secondary endpoints included overall survival and treatment tolerability. Lung function trajectories were analyzed using mixed-effects models, and survival was assessed using Kaplan–Meier analysis and Cox regression. A total of 125 patients were included, of whom 70 (56%) received antifibrotic therapy. Patients in the antifibrotic group had a progressive and more severe disease at baseline, including lower DLCO. The annualized FVC decline significantly slowed after initiation of antifibrotic therapy compared with the pre-treatment period (− 9.25% vs. − 1.37% predicted per year, p < 0.001). Median survival in the overall cohort was 32 months, with no statistically significant survival difference between groups. Adverse events occurred in 42% of treated patients and frequently led to treatment discontinuation. In this multicenter cohort of patients with PPFE, antifibrotic therapy was associated with a significant reduction in FVC decline compared with the pre-treatment period. Treatment was frequently limited by tolerability. Prospective studies are needed to clarify the efficacy and safety of antifibrotic therapies in PPFE.