抽象
BackgroundA randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown.
MethodsThis 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (DLCO)和6分钟的步行距离(6MWD),无进展的存活(PFS),急性加重的发病率和耐受性。
结果81名患者在1:1的比例中随机分配,接受Pirfenidone加入的N-乙酰半胱氨酸(n = 41)或Pirfenidone(n = 40)。FVC的48周变化率分别为-300mL和-123mL(差异-178ml,95%CI -324--31mL; P = 0.018)。串行变化DLCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups.
Conclusions用吸入的N-乙酰琥珀酮和Pirefenidone的组合处理可能导致IPF的更糟糕的结果。
抽象
We compared the efficacy of pirfenidone plus inhaled N-acetylcysteine with results for pirfenidone alone for IPF. Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.https://bit.ly/3eWEbvW
Footnotes
This article has an editorial commentary:https://doi.org/10.1183/13993003.03551-2020
This phase 3 trial was registered with the University Hospital Medical Information Network (UMIN) (registration number: UMIN000015508). No provision has been made for individual participant data to be publicly available
利益冲突:S. Sakamoto没有什么可披露的。
Conflict of interest: K. Kataoka has nothing to disclose.
兴趣冲突:Y. Kondoh报告顾问委员会费用和个人费用Asahi Kasei Pharma Corp.,Boehringer Ingelheim Co. Ltd和Shionogi&Co. Ltd;Janssen Pharmaceutical K.K的咨询委员会费用;埃索林·药业有限公司,Mitsubishi Tanabe Pharma和Novartis Pharma K.k的个人费用和个人费用。
利益冲突:M. Kato没有什么可披露的。
Conflict of interest: M. Okamoto has nothing to disclose.
利益冲突:H. Mukae在研究期间向Shionogi&Co,Ltd的赠款和个人费用报告了Shionogi&Co,Ltd。
Conflict of interest: M. Bando reports personal fees from Shionogi & Co, Ltd, outside the submitted work.
Conflict of interest: T. Suda has nothing to disclose.
兴趣冲突:K. Yatera报告来自Kirigaoka Tsuda医院,Tochiku医院,Hagiwara Central医院,Kurate医院,Saiseikai Yamaguchi Hospital,Teijin Home Healthcare Limited,Teaho Pharmaceutical Co. Ltd,Daiichi Sankyo Company,Limited, GlaxoSmithKline K.K, Pfizer Japan Inc., Taisho Pharma Co. Ltd, MSD K.K, Novartis Pharma K.K, Nippon Boehringer Ingelheim Co. Ltd, Daiwa Securities Health Foundation, Actelion Pharmaceuticals Japan Ltd, Astellas Pharma Inc., AstraZeneca K.K, Eisai Co., Ltd, Shionogi & Co., Ltd, KYORIN Pharmaceutical Co. Ltd, Taisho Pharma Co. Ltd, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co. Ltd, Chugai Pharmaceutical Co. Ltd, Teijin Pharma Limited, and Eli Lilly Japan K.K, outside the submitted work.
利益冲突:Y. Tanino没有什么可披露的。
利益冲突:T. Kishaba没有什么可披露的。
Conflict of interest: N. Hattori has nothing to disclose.
Conflict of interest: Y. Taguchi has nothing to disclose.
利益冲突:T. Saito没有什么可披露的。
Conflict of interest: Y. Nishioka reports grants and personal fees from Shionogi & Co. Ltd, during the conduct of the study; and grants and personal fees from Nippon Boehringer Ingelheim Co. Ltd, MSD K.K, Ono Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, Asahi Kasei Pharma Corporation and Eli Lilly Japan K.K, and grants from Bonac Corporation, outside the submitted work.
Conflict of interest: K. Kuwano has nothing to disclose.
Conflict of interest: K. Kishi reports personal fees from Shionogi, outside the submitted work.
Conflict of interest: N. Inase has nothing to disclose.
兴趣冲突:S. Sasaki没有什么可披露的。
Conflict of interest: H. Takizawa has nothing to disclose.
Conflict of interest: T. Johkoh has nothing to disclose.
利益冲突:F. Sakai没有什么可披露的。
Conflict of interest: S. Homma has nothing to disclose.
Support statement: This study was supported by research grants from the Ministry of Health, Labour and Welfare of Japan and the study group for strategic exploration of drug seeds for Diffuse Lung Disease and construction of clinical evidence of the Japan Agency for Medical Research and Development (AMED) (15ek0109064h0002 and 16ek0109064h0003). Funding information for this article has been deposited with theCrossref Funder Registry.
- Received2020年2月18日。
- AcceptedJuly 16, 2020.
- Copyright ©ERS 2021