TY - JOUR T1 - Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00348-2020 SP - 2000348 AU - Susumu Sakamoto AU - Kensuke Kataoka AU - Yasuhiro Kondo AU - Motoyasu Kato AU - Masaki Okamoto AU - Hiroshi Mukae AU - Masashi Bando AU - Takafumi Suda AU - Kazuhiro Yatera AU - Yoshinori Tanino AU - Tomoo Kishaba AU - Noboru Hattori AU - Yoshio Taguchi AU - Takefumi Saito AU - Yasuhiko Nishioka AU - Kazuyoshi Kuwano AU - Kazuma Kishi AU - Naohiko Inase AU - Shinichi Sasaki AU - Hajime Takizawa AU - Takeshi Johkoh AU - Fumikazu Sakai AU - Sakae Homma AU - the Diffuse Lung Diseases Research Group of the Ministry of Health, Labour and Welfare, Japan Y1 - 2020/01/01 UR - http://erj.ersjournals.com/content/early/2020/07/16/13993003.00348-2020.abstract N2 - Background A 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.Methods This 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 endpoint was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in carbon monoxide diffusing capacity (DLco), and 6-minute walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability.Results A total of 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was −300 mL and −123 mL, respectively (difference, –178 mL; 95% CI, –324 to –31; p=0.018). Serial change in 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 Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Sakamoto has nothing to disclose.Conflict of interest: Dr. Kataoka has nothing to disclose.Conflict of interest: Dr Kondoh reports advisory board fees and personal fees from Asahi Kasei Pharma Corp., Boehringer Ingelheim Co., Ltd., and Shionogi & Co.,, Ltd., and advisory board fees from Janssen Pharmaceutical K.K., personal fees from Eisai inc., personal fees from KYORIN Pharmaceutical Co., Ltd., personal fees from Mitsubishi Tanabe Pharma, personal fees from Novartis Pharma K.K., outside the presentation work.Conflict of interest: Dr. Kato has nothing to disclose.Conflict of interest: Dr. Okamoto has nothing to disclose.Conflict of interest: Dr. Mukae reports grants and personal fees from Shionogi, during the conduct of the study.Conflict of interest: Dr. Bando reports personal fees from SHIONOGI & CO., LTD., outside the submitted work.Conflict of interest: Dr. Suda has nothing to disclose.Conflict of interest: Dr. Yatera reports grants from Kirigaoka Tsuda Hospital., grants from Tochiku Hospital., grants from Hagiwara Central Hospital., grants from Kurate Hospital., grants from Saiseikai Yamaguchi hospital., grants from Ono Pharmaceutical Co., Ltd., grants from Teijin Home Healthcare Limited., grants from Taiho Pharmaceutical Co., Ltd., grants from Daiichi Sankyo Company, Limited., grants from GlaxoSmithKline K.K., grants from Pfizer Japan Inc., grants from Taisho Pharma Co., Ltd., grants from MSD K.K., grants from Novartis Pharma K.K., grants from Nippon Boehringer Ingelheim Co.,Ltd., grants from Daiwa Securities Health Foundation., grants from Actelion Pharmaceuticals Japan Ltd., grants from Astellas Pharma Inc., grants from AstraZeneca K.K., grants from Eisai Co., Ltd., grants from Shionogi & Co., Ltd., grants from KYORIN Pharmaceutical Co.,Ltd., grants from Taisho Pharma Co., Ltd., grants from Daiichi Sankyo Company, Limited., grants from Sumitomo Dainippon Pharma Co., Ltd., grants from Chugai Pharmaceutical Co., Ltd., grants from Teijin Pharma Limited., grants from Eli Lilly Japan K.K., outside the submitted work.Conflict of interest: Dr. Tanino has nothing to disclose.Conflict of interest: Dr. Kishaba has nothing to disclose.Conflict of interest: Dr. Hattori has nothing to disclose.Conflict of interest: Dr. Taguchi has nothing to disclose.Conflict of interest: Dr. Saito has nothing to disclose.Conflict of interest: Dr. Nishioka reports grants and personal fees from SHIONOGI & CO., LTD., during the conduct of the study; grants and personal fees from Nippon Boehringer lngelheim Co., Ltd., grants and personal fees from MSD K.K., grants and personal fees from ONO PHARMACEUTICAL CO., LTD., grants and personal fees from TAIHO PHARMACEUTICAL CO., LTD., grants and personal fees from CHUGAI PHARMACEUTICAL CO., LTD., grants and personal fees from ASAHI KASEI PHARMA CORPORATION, grants and personal fees from Eli Lilly Japan K.K., grants from Bonac Corporation, outside the submitted work.Conflict of interest: Dr. Kuwano has nothing to disclose.Conflict of interest: Dr. Kishi reports personal fees from Shionogi, outside the submitted work.Conflict of interest: Dr. Inase has nothing to disclose.Conflict of interest: Dr. Sasaki has nothing to disclose.Conflict of interest: Dr. TAKIZAWA has nothing to disclose.Conflict of interest: Dr. Johkoh has nothing to disclose.Conflict of interest: Dr. Sakai has nothing to disclose.Conflict of interest: Dr. Homma has nothing to disclose. 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