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Diffuse Lung Disease |

Effect of Pirfenidone on All-Cause Mortality in Patients With Idiopathic Pulmonary Fibrosis (IPF): Comparison of Pooled Analysis With Meta-analysis From the ASCEND and CAPACITY Trials FREE TO VIEW

Steven Nathan; Carlo Albera; Williamson Bradford; Ulrich Costabel; Monica Daigl; Klaus-Uwe Kirchgaessler; Roland du Bois; Ian Glaspole; Marilyn Glassberg; Talmadge King; Lisa Lancaster; David Lederer; Carlos Pereira; Jeffrey Swigris; Dominique Valeyre; Paul Noble
Author and Funding Information

Inova Fairfax Hospital, Falls Church, VA; University of Turin, Turin, Italy; InterMune, Inc., Brisbane, CA; Ruhrlandklinik, Essen, Germany; Roche, Basel, Switzerland; Imperial College, London, United Kingdom; Alfred Hospital and Monash University, Melbourne, VIC, Australia; University of Miami Miller School of Medicine, Miami, FL; University of California, San Francisco, CA; Vanderbilt University Medical Center, Nashville, TN; Columbia University Medical Center, New York, NY; Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil; National Jewish Health, Denver, CO; Assistance Publique-Hôpitaux de Paris, Bobigny, France


Chest. 2015;148(4_MeetingAbstracts):363A. doi:10.1378/chest.2250247
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Abstract

SESSION TITLE: Diagnosis and Treatment of IPF

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 26, 2015 at 01:30 PM - 02:30 PM

PURPOSE: Mortality is an important clinical outcome in the evaluation of novel therapies for the treatment of patients with IPF. All-cause mortality (ACM) represents a measure of drug efficacy and safety giving insight into overall clinical benefit. The effect of pirfenidone on ACM was determined in patients from the ASCEND (PIPF-016) and CAPACITY (PIPF-004/-006) Phase 3 trials at weeks 52, 72 and through the end of study. We compared results of pooled and meta-analyses for ACM at all three time points.

METHODS: The patient population (N=1247) from the ASCEND and two CAPACITY trials were used to assess ACM. The results from the 3 trials were combined through pooled and meta-analyses. Pooled analysis was stratified by study. For random-effects meta-analysis, study heterogeneity was assessed by the DerSimonian and Laird method.

RESULTS: In the pooled analysis, patients who received pirfenidone had a 48% relative reduction in the risk of ACM within 52 weeks compared with patients in the placebo group. ACM occurred in 22/623 (3.5%) patients in the pirfenidone group compared with 42/624 (6.7%) in the placebo group (HR 0.52; 95% CI, 0.31-0.87; P=0.0107). Over the 72 weeks following randomization, a 37% relative reduction in the risk of death was observed among patients receiving pirfenidone compared with placebo (32/623 [5.1%] vs 50/624 [8.0%]; HR 0.63; 95% CI, 0.41-0.98; P=0.0404). In the end of study analysis, a consistent trend over time was observed to week 120; the relative reduction in ACM risk was 31% favoring pirfenidone (38/623 [6.1%]) compared with placebo (54/624 [8.7%]) (HR 0.69; 95% CI, 0.46-1.05, P=0.0789). For the meta-analysis the relative reduction in risk of ACM for patients in the pirfenidone compared with those in the placebo group at weeks 52, 72 and through end of study was 48%, 36% and 31%, respectively (week 52, HR 0.52 0.31-0.88; P=0.0138; week 72, HR 0.64 0.41-0.99, P=0.0459; end of study, HR 0.69 [0.46-1.05], P=0.0861). There was no evidence of heterogeneity between studies in the three analyses.

CONCLUSIONS: Both pooled and meta-analyses of data from the ASCEND and CAPACITY trials consistently favored pirfenidone in reducing the risk of ACM in patients with IPF over time. These findings highlight the robustness of pooled data analyses in evaluating drug efficacy outcomes in the pirfenidone phase 3 trials.

CLINICAL IMPLICATIONS: Results of these alternative analytical approaches further support a pirfenidone treatment effect on ACM that is consistent across study populations and study time points.

DISCLOSURE: Steven Nathan: Consultant fee, speaker bureau, advisory committee, etc.: InterMune/Roche/Genentech Carlo Albera: Consultant fee, speaker bureau, advisory committee, etc.: InterMune Williamson Bradford: Employee: InterMune Ulrich Costabel: Consultant fee, speaker bureau, advisory committee, etc.: InterMune, Consultant fee, speaker bureau, advisory committee, etc.: BI, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Consultant fee, speaker bureau, advisory committee, etc.: Roche, Consultant fee, speaker bureau, advisory committee, etc.: Gilead Monica Daigl: Employee: Roche Roland du Bois: Consultant fee, speaker bureau, advisory committee, etc.: GSK, Consultant fee, speaker bureau, advisory committee, etc.: Roche, Consultant fee, speaker bureau, advisory committee, etc.: Asahi Ian Glaspole: Consultant fee, speaker bureau, advisory committee, etc.: Astra-Zeneca, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: InterMune Marilyn Glassberg: Consultant fee, speaker bureau, advisory committee, etc.: Roche/InterMune, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim Talmadge King: Consultant fee, speaker bureau, advisory committee, etc.: InterMune, Consultant fee, speaker bureau, advisory committee, etc.: ImmuneWorks, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Glaxo Smith Kline, Consultant fee, speaker bureau, advisory committee, etc.: Daiichi Sankyo, Consultant fee, speaker bureau, advisory committee, etc.: Tracon Klaus-Uwe Kirchgaessler: Employee: Roche Lisa Lancaster: Consultant fee, speaker bureau, advisory committee, etc.: InterMune, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim David Lederer: Consultant fee, speaker bureau, advisory committee, etc.: Roche, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Gilead, Consultant fee, speaker bureau, advisory committee, etc.: XVIVO Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: ImmuneWorks Jeffrey Swigris: Consultant fee, speaker bureau, advisory committee, etc.: Roche/Genentech/InterMune Dominique Valeyre: Consultant fee, speaker bureau, advisory committee, etc.: InterMune, Consultant fee, speaker bureau, advisory committee, etc.: Boerhinger-Ingelheim Paul Noble: Consultant fee, speaker bureau, advisory committee, etc.: InterMune, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Genentech, Consultant fee, speaker bureau, advisory committee, etc.: GSK, Consultant fee, speaker bureau, advisory committee, etc.: Moerae Matrix The following authors have nothing to disclose: Carlos Pereira

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