• Steven D Nathan, Ulrich Costabel, Carlo Albera, Jürgen Behr, Wim A Wuyts, Klaus-Uwe Kirchgaessler, John L Stauffer, Elizabeth Morgenthien, Willis Chou, Susan L Limb, and Paul W Noble.
• Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, 8110 Gatehouse Road, Falls Church, VA, 22042, USA. Electronic address: Steven.Nathan@inova.org.
• Respir Med. 2019 Jul 1; 153: 44-51.

BackgroundPatients 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%.MethodsPatients 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.ResultsAt 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.ConclusionPirfenidone 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 Registrationclinicaltrials. gov (ASCEND: NCT01366209; CAPACITY: NCT00287716; NCT00287729).Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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