title: Efficacy of pirfenidone and disease severity of idiopathic pulmonary fibrosis: Extended analysis of phase III trial in Japan.
abstract: BACKGROUND
  A phase III clinical trial of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) in Japan has revealed that pirfenidone attenuated the decline in vital capacity (VC) and improved progression-free survival (PFS). We conducted an extended analysis of the pirfenidone trial to investigate its efficacy with respect to IPF severity in the trial population.
  
  
  METHODS
  Patients in the phase III trial were stratified by baseline pulmonary functions including %VC predicted, %diffusion capacity for carbon monoxide predicted, and oxygen saturation by pulse oximetry on exertion and were categorized into mild, moderate, and severe groups of functional impairment. The efficacy of pirfenidone for VC and PFS over 52 weeks was compared among the three sub-populations.
  
  
  RESULTS
  Of 264 patients, 102 (39%), 90 (34%), and 72 patients (27%) were classified as having mild, moderate, and severe grades of functional impairment, respectively. This classification was associated with arterial oxygen partial pressure at rest and degree of dyspnea at baseline. While pirfenidone attenuated VC decline at all grades of severity, covariance analysis revealed pirfenidone to have better efficacy in the sub-population with mild-grade IPF. Mixed model repeated measures analysis confirmed that pirfenidone markedly attenuated VC decline in patients with mild-grade IPF compared to its effects in patients with moderate or severe IPF. Pirfenidone also improved PFS markedly in patients with mild-grade IPF.
  
  
  CONCLUSIONS
  This extended analysis suggested that pirfenidone exerted better therapeutic effects in patients with milder IPF. Further analysis with a larger population is needed to confirm these results.
authors.affiliation: Department of Respiratory Medicine, Tenri Hospital, Tenri, Nara 632-8552, Japan. Electronic address: ytaguchi@tenriyorozu.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taguchi
authors.affiliation: Department of Respiratory Medicine, Tohoku Pharmaceutical University, Japan. Electronic address: ebinam@hosp.tohoku-pharm.ac.jp.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.affiliation: Department of Respiratory Medicine, Tenri Hospital, Tenri, Nara 632-8552, Japan. Electronic address: hassy@tenriyorozu.jp.
authors.forename: Seishu
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan. Electronic address: Ogura@kanagawa-junko.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogura
authors.affiliation: Department of Pulmonary Medicine and Oncology, Nippon Medical School, Japan. Electronic address: azuma_arata@yahoo.co.jp.
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Japan. Electronic address: hiro-tosei-lung@kkd.biglobe.ne.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Japan. Electronic address: konyasu2003@yahoo.co.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kondoh
authors.affiliation: Center for Preventive Medicine, Saiseikai Kumamoto Hospital, Japan. Electronic address: suga-taka-0825@rose.odn.ne.jp.
authors.forename: Moritaka
authors.initials: M
authors.lastname: Suga
authors.affiliation: Third Department of Internal Medicine, Sapporo Medical University Hospital, Japan. Electronic address: htaka@sapmed.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Respiratory Medicine, Nakata Clinic, Japan. Electronic address: nakata@nakata-clinic.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Japan. Electronic address: sugiyuki@jichi.ac.jp.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Japan Anti-Tuberculosis Association, Japan. Electronic address: skudou@jatahq.org.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Japan Anti-Tuberculosis Association, Japan. Electronic address: toshinkw47@gmail.com.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D011728:Pyridones / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone
keywords: Disease severity; Idiopathic pulmonary fibrosis; Pirfenidone; Progression-free survival; Vital capacity