Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases: Subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial. (October 2021)

• Record Type: Journal Article
• Authors: Inoue, Yoshikazu; Suda, Takafumi; Kitamura, Hideya; Okamoto, Masaki; Azuma, Arata; Inase, Naohiko; Kuwana, Masataka; Makino, Shigeki; Nishioka, Yasuhiko; Ogura, Takashi; Takizawa, Ayako; Ugai, Hiroyuki; Stowasser, Susanne; Schlenker-Herceg, Rozsa; Takeuchi, Tsutomu
• Is Part Of: Respiratory medicine. Volume 187(2021)
• Publication Date: 2021-10
• Subjects: INBUILD -- Japan -- Lung diseases -- Interstitial -- Nintedanib -- Pulmonary fibrosis; AE adverse event -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- BID twice daily -- BL baseline -- BMI body mass index -- CI confidence interval -- DLco diffusing capacity of the lung for carbon monoxide -- DMARD disease-modifying anti-rheumatic drug -- FVC forced vital capacity -- HR hazard ratio -- HRCT high-resolution computed tomography -- ILD interstitial lung disease -- IPAF interstitial pneumonia with autoimmune features -- IPF idiopathic pulmonary fibrosis -- K-BILD King's Brief Interstitial Lung Disease questionnaire -- SD standard deviation -- SSc systemic sclerosis -- UIP usual interstitial pneumonia; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2021.106574
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: Background: The efficacy of nintedanib in progressive fibrosing interstitial lung diseases (ILDs) was demonstrated in the randomised, double-blind, placebo-controlled INBUILD trial. This subgroup analysis evaluated the efficacy and safety of nintedanib in the Japanese population. Methods: Patients with progressive fibrosing ILDs (evaluated by physicians within 24 months of screening) were randomised (1:1) to twice-daily 150-mg nintedanib or placebo; treatment continued until the last patient completed 52 weeks. The primary endpoint was the annual rate of decline in forced vital capacity (FVC) over 52 weeks. Time-to-first acute ILD exacerbation or death and time-to-death up until the last patient had completed the week 52 visit were evaluated. This subgroup analysis included 108 Japanese patients. Results: The adjusted annual rates of FVC decline (mL/year) over 52 weeks for Japanese patients were −148.31 (nintedanib) and −240.36 (placebo), adjusted difference: 92.05 (95% CI: −10.69–194.80) and for non-Japanese patients were −67.41 (nintedanib) and −177.65 (placebo), adjusted difference: 110.24 (95% CI: 64.97–155.52). No heterogeneity in treatment effect between Japanese and non-Japanese subgroups was observed (treatment-by-subgroup interaction, p = 0.75). The risks of "acute exacerbation or death" (hazard ratio, 0.30 [95% CI: 0.10–0.91]) and mortality (hazard ratio, 0.54 [95% CI: 0.14–2.11]) in Japanese patients were numerically lower for nintedanib than placebo. There were no new or unexpected safety findings. Conclusions: In Japanese patients, nintedanib slowed ILD progression, evidenced by a reduction in the annual rate of decline in FVC vs placebo. The efficacy and safety of nintedanib in Japanese patients were consistent with the overall INBUILD population. Clinicaltrials.gov: NCT02999178 (21-Dec-2016). Highlights: Chronic fibrosing interstitial lung diseases (ILDs) have significant mortality and morbidity. Nintedanib, a small molecule inhibitor of selected tyrosine kinases, is approved for ILD treatment. The efficacy of nintedanib for ILD was shown in the phase 3 randomised controlled INBUILD trial. The efficacy and safety of nintedanib in the Japanese subpopulation was similar to INBUILD overall.