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

Respir Med. 2021 Oct:187:106574. doi: 10.1016/j.rmed.2021.106574. Epub 2021 Aug 12.

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).

Keywords: INBUILD; Interstitial; Japan; Lung diseases; Nintedanib; Pulmonary fibrosis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Disease Progression
  • Double-Blind Method
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / mortality
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Indoles / administration & dosage*
  • Indoles / therapeutic use*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / mortality
  • Lung Diseases, Interstitial / physiopathology
  • Safety
  • Time Factors
  • Treatment Outcome
  • Vital Capacity

Substances

  • Indoles
  • nintedanib

Associated data

  • ClinicalTrials.gov/NCT02999178