Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment

Respir Med. 2019 Jul;153:44-51. doi: 10.1016/j.rmed.2019.04.016. Epub 2019 Apr 24.


Background: Patients with idiopathic pulmonary fibrosis (IPF) demonstrate a range of lung function impairment. However, the efficacy of antifibrotics compared with placebo has not been assessed in patients with more advanced disease. This post-hoc analysis investigated the efficacy and safety of pirfenidone versus placebo in patients with IPF and more advanced lung function impairment, defined as percent predicted forced vital capacity (%FVC) < 50% and/or percent predicted carbon monoxide diffusing capacity <35%.

Methods: Patients randomised to pirfenidone 2,403 mg/day or placebo in the ASCEND (NCT01366209) and CAPACITY (NCT00287716; NCT00287729) trials with more advanced baseline lung function impairment (pirfenidone, n = 90; placebo, n = 80) were included. Mortality, lung function, hospitalisation, exercise capacity and dyspnoea were investigated over 52 weeks.

Results: At Week 52 versus placebo, pirfenidone was associated with significantly lower risks of all-cause mortality (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.09-0.86; p=0.0180), ≥10% absolute %FVC decline or all-cause mortality (HR 0.40; 95% CI 0.23-0.69; p=0.0006) and ≥10% absolute %FVC decline or respiratory-related hospitalisation or all-cause mortality (HR 0.46; 95% CI 0.28-0.76; p=0.0018). At Week 52, median treatment differences favouring pirfenidone were 36.7 m for 6-min walk distance and -8.0 points for the University of California-San Diego Shortness of Breath Questionnaire total score. Treatment-emergent adverse events (TEAEs) led to discontinuation in 14.4% and 21.3% of patients with pirfenidone and placebo, respectively.

Conclusion: Pirfenidone demonstrated clinically relevant benefits across multiple domains in patients with IPF and more advanced disease without an increased risk of discontinuation due to TEAEs.

Clinical trials registration: clinicaltrials. gov (ASCEND: NCT01366209; CAPACITY: NCT00287716; NCT00287729).

Keywords: Dyspnoea; Idiopathic pulmonary fibrosis; Mortality; Pirfenidone.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Carbon Monoxide / metabolism
  • Case-Control Studies
  • Dyspnea / drug therapy
  • Dyspnea / epidemiology
  • Exercise Tolerance / drug effects
  • Female
  • Hospitalization / trends
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / mortality
  • Idiopathic Pulmonary Fibrosis / physiopathology*
  • Male
  • Middle Aged
  • Mortality / trends
  • Placebos / administration & dosage
  • Pulmonary Diffusing Capacity / drug effects
  • Pyridones / administration & dosage
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Respiratory Function Tests / methods
  • Treatment Outcome
  • Vital Capacity / drug effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Placebos
  • Pyridones
  • Carbon Monoxide
  • pirfenidone

Associated data

  • ClinicalTrials.gov/NCT01366209
  • ClinicalTrials.gov/NCT00287716
  • ClinicalTrials.gov/NCT00287729