Sakamoto S, Kataoka K, Kondoh Y, Kato M, Okamoto M, Mukae H, Bando M, Suda T, Yatera K, Tanino Y, Kishaba T, Hattori N, Taguchi Y, Saito T, Nishioka Y, Kuwano K, Kishi K, Inase N, Sasaki S, Takizawa H, Johkoh T, Sakai F, and Homma S
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 end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide ( D LCO ) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability., Results: 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--31 mL; p=0.018). Serial change in D LCO , 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., Competing Interests: Conflict of interest: S. Sakamoto has nothing to disclose. Conflict of interest: K. Kataoka has nothing to disclose. Conflict of interest: Y. Kondoh reports advisory board fees and personal fees from Asahi Kasei Pharma Corp., Boehringer Ingelheim Co. Ltd and Shionogi & Co. Ltd; advisory board fees from Janssen Pharmaceutical K.K; and personal fees from Eisai Inc., Kyorin Pharmaceutical Co. Ltd, Mitsubishi Tanabe Pharma and Novartis Pharma K.K, outside the submitted work. Conflict of interest: M. Kato has nothing to disclose. Conflict of interest: M. Okamoto has nothing to disclose. Conflict of interest: H. Mukae reports grants and personal fees from Shionogi & Co, Ltd, during the conduct of the study. 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. Conflict of interest: K. Yatera reports grants from Kirigaoka Tsuda Hospital, Tochiku Hospital, Hagiwara Central Hospital, Kurate Hospital, Saiseikai Yamaguchi Hospital, Ono Pharmaceutical Co. Ltd, Teijin Home Healthcare Limited, Taiho 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. Conflict of interest: Y. Tanino has nothing to disclose. Conflict of interest: T. Kishaba has nothing to disclose. Conflict of interest: N. Hattori has nothing to disclose. Conflict of interest: Y. Taguchi has nothing to disclose. Conflict of interest: T. Saito has nothing to disclose. 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. Conflict of interest: S. Sasaki has nothing to disclose. Conflict of interest: H. Takizawa has nothing to disclose. Conflict of interest: T. Johkoh has nothing to disclose. Conflict of interest: F. Sakai has nothing to disclose. Conflict of interest: S. Homma has nothing to disclose., (Copyright ©ERS 2021.)