Risk factors for acute exacerbation of idiopathic pulmonary fibrosis – Extended analysis of pirfenidone trial in Japan

• Published in: Respiratory investigation Vol. 53; no. 6; pp. 271 - 278
• Main Authors: Kondoh, Yasuhiro, Taniguchi, Hiroyuki, Ebina, Masahito, Azuma, Arata, Ogura, Takashi, Taguchi, Yoshio, Suga, Moritaka, Takahashi, Hiroki, Nakata, Koichiro, Sugiyama, Yukihiko, Kudoh, Shoji, Nukiwa, Toshihiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2015
• Subjects: Absolute decline in VC; Acute Disease; Acute exacerbation; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Clinical Trials, Phase III as Topic; Disease Progression; Female; Humans; Idiopathic pulmonary fibrosis (IPF); Idiopathic Pulmonary Fibrosis - drug therapy; Idiopathic Pulmonary Fibrosis - physiopathology; Internal Medicine; Male; Middle Aged; Multivariate Analysis; Oxygen Consumption; Proportional Hazards Models; Pulmonary Alveoli - metabolism; Pulmonary/Respiratory; Pyridones - therapeutic use; Relative decline in VC; Risk factor; Risk Factors; Vital Capacity; Absolute decline in VC; Relative decline in VC; Idiopathic pulmonary fibrosis (IPF); Acute exacerbation; Risk factor
• ISSN: 2212-5345; 2212-5353
• DOI: 10.1016/j.resinv.2015.04.005

Abstract Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a lifethreatening event and one of the important endpoints in clinical trials involving IPF. Despite this, there has been little evaluation of the potential risk factors for AE-IPF in clinical trials. We evaluated the risk factors for AE-IPF in a phase III clinical trial of pirfenidone in Japanese IPF patients. Methods The study population comprised 267 patients. The effects of various baseline characteristics as possible risk factors for AE-IPF during the study, as well as those of a ≥10% decline in percent vital capacity (%VC) within 6 months, were evaluated using Cox׳s proportional hazard model. The ≥10% decline in %VC was calculated in two ways: (1) an absolute decline (e.g. from 60% predicted to 50%); and (2) a relative decline (e.g. from 60% predicted to 54%). Results Over 52 weeks, 14 patients experienced AE-IPF. Univariate analysis using Cox׳s proportional hazards model showed that both relative and absolute ≥10% decline in %VC within 6 months were significant risk factors for AE-IPF. Stepwise multivariate analysis demonstrated that absolute or relative decline in both %VC and alveolar to arterial oxygen pressure difference (AaDO2 ) were significant risk factors for AE. The model using absolute decline [Hazard Ration (HR)=7.405, p =0.0007] and baseline AaDO2 (HR=1.063, p =0.0266) had a better fit than the model using relative decline and baseline AaDO2. Conclusions Rapid %VC decline (≥10% within 6 months), and high baseline AaDO2 , may be risk factors for AE-IPF.