Risk factors for acute exacerbation of idiopathic pulmonary fibrosis--Extended analysis of pirfenidone trial in Japan.
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.
['Kondoh|Yasuhiro|Y|', 'Taniguchi|Hiroyuki|H|', 'Ebina|Masahito|M|', 'Azuma|Arata|A|', 'Ogura|Takashi|T|', 'Taguchi|Yoshio|Y|', 'Suga|Moritaka|M|', 'Takahashi|Hiroki|H|', 'Nakata|Koichiro|K|', 'Sugiyama|Yukihiko|Y|', 'Kudoh|Shoji|S|', 'Nukiwa|Toshihiro|T|']
D000208:Acute Disease D000328:Adult D000368:Aged D000894:Anti-Inflammatory Agents, Non-Steroidal D017326:Clinical Trials, Phase III as Topic D018450:Disease Progression D005260:Female D006801:Humans D054990:Idiopathic Pulmonary Fibrosis D008297:Male D008875:Middle Aged D015999:Multivariate Analysis D010101:Oxygen Consumption D016016:Proportional Hazards Models D011650:Pulmonary Alveoli D011728:Pyridones D012307:Risk Factors D014797:Vital Capacity
Risk factor Acute exacerbation Absolute decline in VC Idiopathic pulmonary fibrosis (IPF) Relative decline in VC