Nerandomilast in Patients with Progressive Pulmonary Fibrosis

作者：Toby M. Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna‐Maria Hoffmann‐Vold, Michael Kreuter, Justin M. Oldham, Luca Richeldi, Claudia Valenzuela, Marlies Wijsenbeek, Emmanuelle Clerisme-Beaty, Carl Coeck, Heng Gu, Ivana Ritter, Arno Schlosser, Susanne Stowasser, Florian Voß, Gerrit Weimann, Donald F. Zoz, Fernando J. Martínez · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2503643 · 被引用次数：166 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Phosphodiesterase function and regulation、Pulmonary Hypertension Research and Treatments

BACKGROUND: Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. Nerandomilast has been shown to slow the progression of idiopathic pulmonary fibrosis, but an assessment of its effects in other types of progressive pulmonary fibrosis is needed. METHODS: In a phase 3, double-blind trial, we randomly assigned patients with progressive pulmonary fibrosis in a 1:1:1 ratio to receive nerandomilast at a dose of 18 mg twice daily, nerandomilast at a dose of 9 mg twice daily, or placebo, with stratification according to background therapy (nintedanib vs. none) and fibrotic pattern on high-resolution computed tomography (usual interstitial pneumonia-like pattern vs. other patterns). The primary end point was the absolute change from baseline in the forced vital capacity (FVC), measured in milliliters, at week 52. RESULTS: A total of 1176 patients received at least one dose of nerandomilast or placebo, of whom 43.5% were taking background nintedanib therapy at baseline. The adjusted mean change in the FVC at week 52 was -98.6 ml (95% confidence interval [CI], -123.7 to -73.4) in the nerandomilast 18-mg group, -84.6 ml (95% CI, -109.6 to -59.7) in the nerandomilast 9-mg group, and -165.8 ml (95% CI, -190.5 to -141.0) in the placebo group. The adjusted difference between the nerandomilast 18-mg group and the placebo group was 67.2 ml (95% CI, 31.9 to 102.5; P<0.001), and the adjusted differe...