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

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

Author information

1
Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, 8110 Gatehouse Road, Falls Church, VA, 22042, USA. Electronic address: Steven.Nathan@inova.org.
2
Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Tüschener Weg 40, 45239, Essen, Germany. Electronic address: ulrich.costabel@rlk.uk-essen.de.
3
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. Electronic address: carlo.albera@yahoo.it.
4
Department of Internal Medicine V, Comprehensive Pneumology Center, University of Munich (LMU) and Asklepios Fachkliniken München-Gauting, a member of the German Center for Lung Research (DZL), Robert-Koch-Allee 2, 82131, Gauting, Munich, Germany. Electronic address: juergen.behr@med.uni-muenchen.de.
5
Department of Respiratory Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: wim.wuyts@uzleuven.be.
6
F. Hoffmann-La Roche, Ltd., Konzern-Hauptsitz, Grenzacherstrasse 124, CH-4070, Basel, Switzerland. Electronic address: klaus-uwe.kirchgaessler@roche.com.
7
Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Electronic address: stauffer.john@gene.com.
8
Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Electronic address: morgente@gene.com.
9
Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Electronic address: willis.chou@att.net.
10
Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Electronic address: limb.susan@gene.com.
11
Department of Medicine, Cedars-Sinai Medical Center, 87000 Beverly Boulevard, Los Angeles, CA, 90048, USA. Electronic address: paul.noble@cshs.org.

Abstract

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

PMID:
31153107
DOI:
10.1016/j.rmed.2019.04.016
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