title: The clinical significance of 5% change in vital capacity in patients with idiopathic pulmonary fibrosis: extended analysis of the pirfenidone trial.
abstract: BACKGROUND
  Our phase III clinical trial of pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) revealed the efficacy in reducing the decline of vital capacity (VC) and increasing the progression-free survival (PFS) time by pirfenidone. Recently, marginal decline in forced VC (FVC) has been reported to be associated with poor outcome in IPF. We sought to evaluate the efficacy of pirfenidone from the aspects of 5% change in VC.
  
  
  METHODS
  Improvement ratings based on 5% change in absolute VC, i.e., "improved (VC ≥ 5% increase)", "stable (VC < 5% change)", and "worsened (VC ≥ 5% decrease)" at month 3, 6, 9 and 12 were compared between high-dose pirfenidone (1800 mg/day; n = 108) and placebo (n = 104) groups, and (high-dose and low-dose (1200 mg/day; n = 55)) pirfenidone (n = 163) and placebo groups. PFS times with defining the disease progression as death or a ≥ 5% decline in VC were also compared between high-dose pirfenidone and placebo groups, and low-dose pirfenidone and placebo groups. Furthermore, considering "worsened" and "non-worsened (improved and stable)" of the ratings at months 3 and 12 as "positive" and "negative", respectively, and the positive and negative predictive values of the ratings were calculated in each group.
  
  
  RESULTS
  In the comparison of the improvement ratings, the statistically significant differences were clearly revealed at months 3, 6, 9, and 12 between pirfenidone and placebo groups. Risk reductions by pirfenidone to placebo were approximately 35% over the study period. In the comparison of the PFS times, statistically significant difference was also observed between pirfenidone and placebo groups. The positive/negative predictive values in placebo and pirfenidone groups were 86.1%/50.8% and 87.1%/71.7%, respectively. Further, the baseline characteristics of patients worsened at month 3 had generally severe impairment, and their clinical outcomes including mortality were also significantly worsened after 1 year.
  
  
  CONCLUSIONS
  The efficacy of pirfenidone in Japanese phase III trial was supported by the rating of 5% decline in VC, and the VC changes at month 3 may be used as a prognostic factor of IPF.
  
  
  BACKGROUND
  This clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13th, 2005 (REGISTRATION NUMBER: JAPICCTI-050121).
authors.affiliation: Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, Japan. hiro-tosei-lung@kkd.biglobe.ne.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kondoh
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Moritaka
authors.initials: M
authors.lastname: Suga
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nakata
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Sato
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
mesh_terms: D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D007564:Japan; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D011728:Pyridones / Q000627:therapeutic use*; D019141:Respiratory System Agents / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects*
chemical_list: D011728:Pyridones; D019141:Respiratory System Agents; C093844:pirfenidone