Published: 5 January 2021

Authors: Susumu Sakamoto, Kensuke Kataoka, Yasuhiro Kondoh, Motoyasu Kato, Masaki Okamoto, Hiroshi Mukae, Masashi Bando, Takafumi Suda, Kazuhiro Yatera, Yoshinori Tanino, Tomoo Kishaba, Noboru Hattori, Yoshio Taguchi, Takefumi Saito, Yasuhiko Nishioka, Kazuyoshi Kuwano, Kazuma Kishi, Naohiko Inase, Shinichi Sasaki, Hajime Takizawa, Takeshi Johkoh, Fumikazu Sakai, Sakae Homma the Diffuse Lung Diseases Research Group of the Ministry of Health, Labour and Welfare, Japan

Source: This abstract has been sourced from NZ Respiratory Research Review Issue 189


    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 (DLCO) 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 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.

    Link to abstract

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