Subgroup Analysis for Chinese Patients Included in the INPULSIS® Trials on Nintedanib in Idiopathic Pulmonary Fibrosis
To investigate the efficacy and safety of nintedanib versus placebo in Chinese patients with idiopathic pulmonary fibrosis (IPF).
The INPULSIS® trials consisted of two replicate, randomized, placebo-controlled, double-blind trials comparing nintedanib 150 mg bid with placebo over a 52-week treatment period. The primary endpoint was annual rate of decline in forced vital capacity (FVC); key secondary endpoints were change from baseline in Saint George’s Respiratory Questionnaire’s total score and time to first investigator-reported acute exacerbation. Data from both trials were pooled for the Chinese subgroup analyses.
A total of 101 Chinese patients (nintedanib/placebo: 61/40) were treated. The demographic characteristics were generally balanced between treatment arms. Over 52 weeks, the rate of decline in FVC was lower in nintedanib-treated patients compared with placebo-treated patients in the Chinese subgroup [− 126.43 vs. − 229.82 mL/year; ∆ = 103.39 mL/year (95% confidence interval, CI: − 19.40 to 226.18)]. The proportion of patients with adverse events (AEs) over 52 weeks was similar between treatment arms. The most commonly reported AEs with nintedanib treatment were gastrointestinal symptoms (diarrhoea, nausea, and vomiting).
Nintedanib is clinically efficacious in Chinese patients with IPF with approximately 50% reductions in the rate of decline in FVC, demonstrating slowed disease progression. Similar to the overall INPULSIS® population, nintedanib has a favourable benefit/risk profile in Chinese patients with IPF.
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KeywordsAsians Chinese Efficacy Forced vital capacity Idiopathic pulmonary fibrosis INPULSIS® Nintedanib Randomized controlled trial Respiratory Safety
The authors would like to thank Zhancheng Gao, Peking University People’s Hospital, Beijing; Zhikui Li, Xijing Hospital, 4th Military Medical University, Xi’an; Huanying Wan, Shanghai Ruijin Hospital, Shanghai; Haoyan Wang, Beijing Friendship Hospital, Beijing; Qiming Xiao, Xiangya Hospital, Central South University, Changsha; Wei Zhang, The First Affiliated Hospital of Nanchang University, Nanchang; Xiwei Zheng, General Hospital of Ningxia Medical University, Yinchuan; Huili Zhu, Shanghai Huadong Hospital, Shanghai for their efforts during the trials in China. The authors also thank the participants of the study.
The INPULSIS® trials were funded by Boehringer Ingelheim. The article processing charges were funded by Boehringer Ingelheim.
Medical Writing and/or Editorial Assistance
Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Hui Chin Teoh during the development of this article.
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Jian Kang is the guarantor of this work and, had full access to all the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
Zuojun Xu acted as a principal investigator of the INPULSIS® trials in China, and received investigator fees for the roles. Huiping Li acted as a principal investigator of the INPULSIS® trials in China, and received investigator fees for the roles. Fuqiang Wen acted as a principal investigator of the INPULSIS® trials in China, and received investigator fees for the roles. Chunxue Bai acted as a principal investigator of the INPULSIS® trials in China, and received investigator fees for the roles. Ping Chen acted as a principal investigator of the INPULSIS® trials in China, and received investigator fees for the roles. Jian Kang acted as a principal investigator of the INPULSIS® trials in China, and received investigator fees for the roles. Feng Fan is an employee of Boehringer Ingelheim. Na Hu is an employee of Boehringer Ingelheim. Susanne Stowasser is an employee of Boehringer Ingelheim. None of the listed authors received any payment for their participation in the writing of this manuscript.
Compliance with Ethics Guidelines
This post hoc subgroup analysis is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. The main INPULSIS® trials were conducted in accordance with the principles of the Declaration of Helsinki and the Harmonized Tripartite Guideline for Good Clinical Practice from the International Conference on Harmonization and were approved by local authorities. The clinical protocol was approved by an independent ethics committee or institutional review board at each participating centre. All patients provided written informed consent before study entry.
The datasets generated for this study can be accessed and analysed via application to the Clinical Study Data Request (CSDR) website at https://www.clinicalstudydatarequest.com.
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