@article{4c2fe26022e84cca9eefa4de886ed70e,
title = "Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis",
abstract = "Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P <.0001). Death following one or more progression event occurred less frequently in the pirfenidone group than in the placebo group (2.1% vs 6.3%; P =.0002). Conclusions: Pirfenidone significantly reduced the incidence of multiple progression events and death after a progression event over 12 months of treatment compared with placebo. These findings suggest that continued treatment with pirfenidone confers a benefit despite the occurrence of any single disease progression event. Trial Registry: ClinicalTrials.gov; Nos. NCT01366209, NCT00287716, and NCT00287729; URL: www.clinicaltrials.gov.",
keywords = "disease progression, idiopathic pulmonary fibrosis, interstitial lung diseases, pirfenidone",
author = "Nathan, {Steven D.} and Ulrich Costabel and Ian Glaspole and Glassberg, {Marilyn K.} and Lancaster, {Lisa H.} and Lederer, {David J.} and Pereira, {Carlos A.} and Benjamin Trzaskoma and Morgenthien, {Elizabeth A.} and Limb, {Susan L.} and Wells, {Athol U.}",
note = "Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. D. N. was a member of the ASCEND study steering committee; has served on a scientific advisory board and received research funding from InterMune; has received research funding and served as a consultant for Boehringer Ingelheim, Gilead, and Roche/Genentech; is on the speakers bureau for Roche/Genentech; and his institution has received research funding from Boehringer Ingelheim and Roche/Genentech. U. C. has served as a consultant and speaker for Bayer, Boehringer Ingelheim, and InterMune/Roche; has received grants from Boehringer Ingelheim and InterMune; and has served as a consultant for Biogen, FibroGen, GlaxoSmithKline, Global Blood Therapeutics, and UCB Celltech. I. G. was a member of the ASCEND study steering committee; is cochair of the Australian IPF Registry steering committee; has received grants from Boehringer Ingelheim and Roche; has served as a consultant for AdAlta, Boehringer Ingelheim, and Roche; has served as a speaker for Boehringer Ingelheim and Roche; and his institution has received nonfinancial support from Boehringer Ingelheim. M. K. G. was a member of the ASCEND study steering committee; has served on scientific advisory boards and received research funding from InterMune; serves on the Scientific Advisory Council for the American Lung Association; has served as a consultant for Bellerophon, Boehringer Ingelheim, France Foundation, Patara, and Roche/Genentech; and has received research funding from Roche/Genentech. L. H. L. was a member of the ASCEND study steering committee; has served as a consultant for and has served on scientific advisory boards for Boehringer Ingelheim, Genentech, InterMune, and Veracyte; and has participated as a clinical trial investigator for Afferent, Bayer, Celgene, Boehringer Ingelheim, FibroGen, Genentech, Gilead, Stromedix, and Veracyte. D. J. L. was a member of the ASCEND study steering committee; has served as a consultant for and on scientific advisory boards for Boehringer Ingelheim, Gilead, ImmuneWorks, and InterMune; has served as a consultant for Degge Group, France Foundation, Genentech, Patara, PharmAkea, Philips Respironics, and Veracyte; has received grants from Bayer, FibroGen, and Global Blood Therapeutics; and is an advisor for the Pulmonary Fibrosis Foundation. C. A. P. was a member of the ASCEND study steering committee and has received a research grant from InterMune. B. T., E. A. M., and S. L. L. are employees of Genentech. A. U. W. has received consultancy or lecturing fees from Actelion, Bayer, Boehringer Ingelheim, Centricorp, Chiesi, Gilead, and InterMune/Roche. Funding Information: FUNDING/SUPPORT: This work was sponsored by F. Hoffmann-La Roche Ltd. and Genentech , Inc. Funding Information: FUNDING/SUPPORT:This work was sponsored by F. Hoffmann-La Roche Ltd. and Genentech, Inc. FUNDING/SUPPORT:This work was sponsored by F. Hoffmann-La Roche Ltd. and Genentech, Inc. Author contributions: S. D. N. takes responsibility for the content of the manuscript, including the data and the analysis. S. D. N. U. C. I. G. M. K. G. L. H. L. D. J. L. C. A. P. B. T. E. A. M. S. L. L. and A. U. W. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis and contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. D. N. was a member of the ASCEND study steering committee; has served on a scientific advisory board and received research funding from InterMune; has received research funding and served as a consultant for Boehringer Ingelheim, Gilead, and Roche/Genentech; is on the speakers bureau for Roche/Genentech; and his institution has received research funding from Boehringer Ingelheim and Roche/Genentech. U. C. has served as a consultant and speaker for Bayer, Boehringer Ingelheim, and InterMune/Roche; has received grants from Boehringer Ingelheim and InterMune; and has served as a consultant for Biogen, FibroGen, GlaxoSmithKline, Global Blood Therapeutics, and UCB Celltech. I. G. was a member of the ASCEND study steering committee; is cochair of the Australian IPF Registry steering committee; has received grants from Boehringer Ingelheim and Roche; has served as a consultant for AdAlta, Boehringer Ingelheim, and Roche; has served as a speaker for Boehringer Ingelheim and Roche; and his institution has received nonfinancial support from Boehringer Ingelheim. M. K. G. was a member of the ASCEND study steering committee; has served on scientific advisory boards and received research funding from InterMune; serves on the Scientific Advisory Council for the American Lung Association; has served as a consultant for Bellerophon, Boehringer Ingelheim, France Foundation, Patara, and Roche/Genentech; and has received research funding from Roche/Genentech. L. H. L. was a member of the ASCEND study steering committee; has served as a consultant for and has served on scientific advisory boards for Boehringer Ingelheim, Genentech, InterMune, and Veracyte; and has participated as a clinical trial investigator for Afferent, Bayer, Celgene, Boehringer Ingelheim, FibroGen, Genentech, Gilead, Stromedix, and Veracyte. D. J. L. was a member of the ASCEND study steering committee; has served as a consultant for and on scientific advisory boards for Boehringer Ingelheim, Gilead, ImmuneWorks, and InterMune; has served as a consultant for Degge Group, France Foundation, Genentech, Patara, PharmAkea, Philips Respironics, and Veracyte; has received grants from Bayer, FibroGen, and Global Blood Therapeutics; and is an advisor for the Pulmonary Fibrosis Foundation. C. A. P. was a member of the ASCEND study steering committee and has received a research grant from InterMune. B. T. E. A. M. and S. L. L. are employees of Genentech. A. U. W. has received consultancy or lecturing fees from Actelion, Bayer, Boehringer Ingelheim, Centricorp, Chiesi, Gilead, and InterMune/Roche. Role of sponsors: The sponsor was involved in the design of the study, the collection and analysis of the data, and the preparation of the manuscript. Other contributions: Support for third-party writing assistance, furnished by Benjamin Ricca, PhD, of Health Interactions, Inc, was provided by F. Hoffmann-La Roche Ltd. Data Sharing: Qualified researchers may request access to individual patient-level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available at https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx. For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm. Additional information: The e-Appendix, e-Figure, and e-Table can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT:This work was sponsored by F. Hoffmann-La Roche Ltd. and Genentech, Inc. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2019",
month = apr,
doi = "10.1016/j.chest.2018.11.008",
language = "English (US)",
volume = "155",
pages = "712--719",
journal = "Diseases of the chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "4",
}