title: Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis.
abstract: The assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.
  
  
  
  The source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.
  
  
  
  A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, -0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).
  
  
  
  Longitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.
  
  
  
  NCT01366209, NCT00287729, NCT00287716.
authors.affiliation: Inova Fairfax Hospital, Heart and Lung Transplant Center, Falls Church, Virginia, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Nathan
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Albera
authors.affiliation: InterMune Inc., Brisbane, California, USA.
authors.forename: Williamson Z
authors.initials: WZ
authors.lastname: Bradford
authors.affiliation: Department of Pneumology/Allergy, Ruhrlandklinik, Essen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.affiliation: Imperial College, London, UK.
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
authors.affiliation: InterMune Inc., Brisbane, California, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Fagan
authors.affiliation: InterMune Inc., Brisbane, California, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fishman
authors.affiliation: Alfred Hospital and Monash University, Melbourne, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Glaspole
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Marilyn K
authors.initials: MK
authors.lastname: Glassberg
authors.affiliation: InterMune Inc., Brisbane, California, USA.
authors.forename: Kenneth F
authors.identifier: 0000-0002-5167-7754
authors.initials: KF
authors.lastname: Glasscock
authors.affiliation: University of California, San Francisco, California, USA.
authors.forename: Talmadge E
authors.initials: TE
authors.lastname: King
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lancaster
authors.affiliation: Columbia University Medical Center, New York, New York, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.affiliation: InterMune Inc., Brisbane, California, USA.
authors.forename: Zhengning
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pereira
authors.affiliation: Interstitial Lung Disease Program, National Jewish Health, Denver, Colorado, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Swigris
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Avicenne University Hospital, Bobigny, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.affiliation: Cedars Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.affiliation: Royal Brompton Hospital, London, UK.
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D011728:Pyridones / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone
keywords: Idiopathic pulmonary fibrosis