TY - JOUR
T1 - Efficacy and safety of nintedanib in Japanese patients with progressive fibrosing interstitial lung diseases
T2 - Subgroup analysis of the randomised, double-blind, placebo-controlled, phase 3 INBUILD trial
AU - Inoue, Yoshikazu
AU - Suda, Takafumi
AU - Kitamura, Hideya
AU - Okamoto, Masaki
AU - Azuma, Arata
AU - Inase, Naohiko
AU - Kuwana, Masataka
AU - Makino, Shigeki
AU - Nishioka, Yasuhiko
AU - Ogura, Takashi
AU - Takizawa, Ayako
AU - Ugai, Hiroyuki
AU - Stowasser, Susanne
AU - Schlenker-Herceg, Rozsa
AU - Takeuchi, Tsutomu
N1 - Funding Information:
TT has received research funding from Astellas, Chugai Pharmaceutical Co., Ltd, Daiichi Sankyo, Takeda, AbbVie, Asahi Kasei Corp., Mitsubishi Tanabe, Pfizer, Eisai, Ayumi Pharmaceutical Corp., Nippon Kayaku, and Novartis, consulting fees from AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, AbbVie, Nippon Kayaku, Janssen, Astellas, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, Taisho Toyama, GlaxoSmithKline, and UCB, and has served on speaker bureaus for AbbVie, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd, Mitsubishi Tanabe, Pfizer, Astellas, Daiichi Sankyo, Eisai, Sanofi, Teijin, Takeda, and Novartis.
Funding Information:
This study was sponsored by Boehringer Ingelheim , manufacturer of nintedanib. Boehringer Ingelheim was involved in the study design, data collection, data analysis, and preparation of the manuscript. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Medical writing assistance was provided by Serina Stretton, PhD, CMPP, and Rebecca Lew, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan . ProScribe's services complied with international guidelines for Good Publication Practice (GPP3).
Funding Information:
YN has received research funding from the Japanese Ministry of Health, Labour and Welfare, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., and Pfizer K.K., and serves on speaker bureaus for AstraZeneca K.K., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co., Ltd., and Pfizer K.K.
Funding Information:
MK has received research funding from Actelion Pharmaceuticals Ltd, consulting fees from Bayer, Nippon Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd, Corbus Pharmaceuticals, and CSL Behring, and serves on speaker bureaus for Actelion Pharmaceuticals Ltd, Nippon Boehringer Ingelheim, and Chugai Pharmaceutical Co., Ltd.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/10
Y1 - 2021/10
N2 - 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).
AB - 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).
KW - INBUILD
KW - Interstitial
KW - Japan
KW - Lung diseases
KW - Nintedanib
KW - Pulmonary fibrosis
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U2 - 10.1016/j.rmed.2021.106574
DO - 10.1016/j.rmed.2021.106574
M3 - Article
AN - SCOPUS:85115372523
VL - 187
JO - British Journal of Tuberculosis and Diseases of the Chest
JF - British Journal of Tuberculosis and Diseases of the Chest
SN - 0954-6111
M1 - 106574
ER -