Yasuhiro Kondoh1, Hiroyuki Taniguchi2, Masahito Ebina3, Arata Azuma4, Takashi Ogura5, Yoshio Taguchi6, Moritaka Suga7, Hiroki Takahashi8, Koichiro Nakata9, Yukihiko Sugiyama10, Shoji Kudoh11, Toshihiro Nukiwa12. 1. Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto, Aichi 489-8642, Japan. Electronic address: konyasu2003@yahoo.co.jp. 2. Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto, Aichi 489-8642, Japan. Electronic address: taniguchi@tosei.or.jp. 3. Department of Respiratory Medicine, Tohoku Pharmaceutical University, 1-12-1, Fukumuro, Miyagino-ku, Sendai 983-8512, Japan. Electronic address: ebinam@hosp.tohoku-pharm.ac.jp. 4. Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyou-ku, Tokyo 113-8603, Japan. Electronic address: azuma_arata@yahoo.co.jp. 5. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1, Tomiokahigashi, Kanazawa-ku, Yokohama 236-0051, Japan. Electronic address: Ogura@kanagawa-junko.jp. 6. Department of Respiratory Medicine, Tenri Hospital, 200, Mishima-cho, Tenri 632-8552, Japan. Electronic address: ytaguchi@tenriyorozu.jp. 7. Center for Preventive Medicine, Saiseikai Kumamoto Hospital, 5-3-1, Tikami, Minami-ku, Kumamoto 861-4193, Japan. Electronic address: suga-taka-0825@rose.odn.ne.jp. 8. Third Department of Internal Medicine, Sapporo Medical University Hospital, 16-291, Minami-ichijo-nishi, Tyuou-ku, Sapporo 060-8543, Japan. Electronic address: htaka@sapmed.ac.jp. 9. Department of Respiratory Medicine, Nakata Clinic, 2-2-1, Naikoucho, Chiyodaku, Tokyo 100-0011, Japan. Electronic address: nakata@nakata-clinic.jp. 10. Department of Medicine, Division of Pulmonary Medicine, Jichi Medical University, 3311-1, Yakushiji, Simono, Tochigi 329-0498, Japan. Electronic address: sugiyuki@jichi.ac.jp. 11. Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyou-ku, Tokyo 113-8603, Japan; Department of Respiratory Medicine, Fukujuji Hospital, 3-1-24, Matsuyama, Kiyose, Tokyo 204-8522, Japan. Electronic address: kudous@fukujuji.org. 12. Department of Respiratory Medicine, Tohoku Pharmaceutical University, 1-12-1, Fukumuro, Miyagino-ku, Sendai 983-8512, Japan; Department of Respiratory Medicine, South Miyagi Medical Center, 38-1, Ohkawara-cho-aza-nishi, Shibata-gun, Miyagi 989-1253, Japan. Electronic address: toshinkw47@gmail.com.
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.
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.
Authors: Paola Faverio; Federica De Giacomi; Luca Sardella; Giuseppe Fiorentino; Mauro Carone; Francesco Salerno; Jousel Ora; Paola Rogliani; Giulia Pellegrino; Giuseppe Francesco Sferrazza Papa; Francesco Bini; Bruno Dino Bodini; Grazia Messinesi; Alberto Pesci; Antonio Esquinas Journal: BMC Pulm Med Date: 2018-05-15 Impact factor: 3.317