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Risk factors for disease progression in idiopathic pulmonary fibrosis
  1. Ganesh Raghu1,
  2. Brett Ley2,
  3. Kevin K Brown3,
  4. Vincent Cottin4,
  5. Kevin F Gibson5,
  6. Robert J Kaner6,
  7. David J Lederer7,
  8. Paul W Noble8,
  9. Jin Woo Song9,
  10. Athol U Wells10,
  11. Timothy P Whelan11,
  12. David A Lynch12,
  13. Stephen M Humphries12,
  14. Emmanuel Moreau13,
  15. Krista Goodman14,
  16. Scott D Patterson14,
  17. Victoria Smith14,
  18. Qi Gong15,
  19. John S Sundy14,
  20. Thomas G O'Riordan14,
  21. Fernando J Martinez16
  1. 1Center for Interstitial Lung Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA
  2. 2Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA
  3. 3Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, Colorado, USA
  4. 4Center for Rare Pulmonary Diseases, Hospices Civils de Lyon, University of Lyon, UMR754, Lyon, France
  5. 5Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  6. 6Department of Clinical Medicine and Genetic Medicine, Weill Cornell Medicine, New York, New York, USA
  7. 7Division of Pulmonary, Allergy, and Critical Care, Columbia University Medical Center, New York, New York, USA
  8. 8Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA
  9. 9Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
  10. 10Department of Medicine, National Heart & Lung Institute, Royal Brompton Hospital, Imperial College, London, UK
  11. 11Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
  12. 12Department of Radiology, National Jewish Health, Denver, Colorado, USA
  13. 13Research and Development, bioMérieux, Lyon, France
  14. 14Clinical Research, Gilead Sciences, Inc, Seattle, Washington, USA
  15. 15Biostatistics, Gilead Sciences, Inc, Foster City, California, USA
  16. 16Department of Medicine, Cornell University, New York City, New York, USA
  1. Correspondence to Professor Ganesh Raghu, Center for Interstitial Lung Diseases, Campus Box 356175, University of Washington Medicine, Seattle, WA 98195, USA; graghu{at}uw.edu

Abstract

In this retrospective study of a randomised trial of simtuzumab in idiopathic pulmonary fibrosis (IPF), prodromal decline in forced vital capacity (FVC) was significantly associated with increased risk of mortality, respiratory and all-cause hospitalisations, and categorical disease progression. Predictive modelling of progression-free survival event risk was used to assess the effect of population enrichment for patients at risk of rapid progression of IPF; C-index values were 0.64 (death), 0.69 (disease progression), and 0.72 (adjudicated respiratory hospitalisation) and 0.76 (all-cause hospitalisation). Predictive modelling may be a useful tool for improving efficiency of clinical trials with categorical end points.

  • idiopathic pulmonary fibrosis
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  • Correction notice This article has been corrected since it published Online First. The second to last sentence has been corrected.

  • Contributors TOR provided the text for the first draft and collated comments for all drafts. QG performed the statistical analysis. FJM, GR and BL provided the text for the first draft. GR, FJM, KKB, DJL and PWN served on the advisory committee that oversaw the primary study. VC, RJK and KFG adjudicated clinical end points. SDP and VS contributed to the LOXL2 biomarker analysis. DAL and SMH analysed the high-resolution CT data. All authors reviewed and provided comments on the final draft of the manuscript. All authors except BL reviewed the study design. Some of the placebo data were presented as an abstract at ATS in 2017.

  • Funding The study was funded by Gilead Sciences, Inc.

  • Competing interests GR has provided consultation for Gilead Sciences, Inc., for this work; for Bellerophon, Biogen, Boehringer Ingelheim, BMS, FibroGen, Gilead Sciences, Inc., Nitto, Promedior, Roche-Genentech, Sanofi-Aventis and Veracyte outside the submitted work; and has received research grants from the National Institutes of Health (NIH) for idiopathic pulmonary fibrosis studies outside the submitted work. BL reports speaker fees from Genentech outside the submitted work. KKB reports grants from the National Heart, Lung, and Blood Institute

    (NHLBI); grants and consulting fees from Actelion; Amgen; and Gilead Sciences, Inc.; and personal fees from Aeolus, Almirall, Altitude Pharma, AstraZeneca, Bayer, Biogen/Stromedix, Boehringer Ingelheim, Celgene, Centocor, FibroGen, Galecto, GlaxoSmithKline, MedImmune, Novartis, Pfizer, Promedior, ProMetic, Roche/Genentech, Sanofi/Genzyme and Veracyte. VC reports personal fees from Actelion, Bayer, Biogen Idec, Boehringer Ingelheim, Gilead Sciences, Inc., GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Pfizer, Roche/InterMune and Sanofi; grants from Actelion, Boehringer Ingelheim, GlaxoSmithKline, Pfizer and Roche; and personal fees from Boehringer Ingelheim outside the submitted work. KFG, PWN and JWS declare no competing interests. RJK reports personal fees from Boehringer Ingelheim, Genentech, MedImmune and Gilead Sciences, Inc.; and other fees from Afferent and Bristol-Myers Squibb outside the submitted work. DJL reports grants from Gilead Sciences, Inc., during the conduct of the study; grants and personal fees from Boehringer Ingelheim; personal fees from Degge Group; France Foundation; Genentech; Gilead Sciences, Inc., and Veracyte; grants from Bayer, FibroGen and Global Blood Therapeutics; and grants, consulting fees and institutional support from Pulmonary Fibrosis Foundation outside the submitted work. AUW reports personal fees from Actelion, Bayer, Boehringer Ingelheim, InterMune and Roche during the conduct of the study. TPW reports grants from Gilead Sciences, Inc., during the conduct of the study; personal fees from Boehringer Ingelheim; Genentech and Gilead Sciences, Inc.; and grants from Boehringer Ingelheim, Celgene, Genentech, Global Blood, Kadmon, Pulmonary Fibrosis Foundation Therapeutics and Sanofi outside the submitted work. DAL reports grants from NHLBI and grants and consulting fees from Boehringer Ingelheim, Parexel, Roche/Genentech, Siemens and Veracyte outside the submitted work. SH reports consulting for Parexel during the conduct of the study and for Boehringer Ingelheim outside this study; and has a patent system and method for automatic detection and quantification of pathology using dynamic feature classification pending to National Jewish Health. EM is an employee of bioMérieux. KFG, SDP, VS, QG and JSS are employees and may hold stock in Gilead Sciences, Inc. At the time of writing, TGOR was an employee of and a stockholder in Gilead Sciences, Inc. FJM reports personal fees from the Adept, Academic Continuing Medical Education, American Thoracic Society, Afferent, Axon Communication, Boehringer Ingelheim, Clarion, Falco, Genentech, Ikaria/Bellerophon, Kadmon, National Association for Continuing Education, Nycomed/Takeda, Pfizer, Potomac and Veracyte; grants from the NIH; nonfinancial support from Biogen/Stromedix, Boehringer Ingelheim, Centocor and Gilead Sciences, Inc.; and other support from Bayer, Boehringer Ingelheim, Genentech and Veracyte during the conduct of the study; grants, personal fees and nonfinancial support from AstraZeneca, GlaxoSmithKline and Nycomed/Takeda; grants and personal fees from Forest; grants from BioScale; personal fees from Amgen, Annenberg, Axon, Boehringer Ingelheim, California Society for Allergy and Immunology, CME Incite, ConCert, Genentech, HayMarket, Ikaria/Bellerophon, Informa, Integritas, InThought, Janssen, Lucid, Methodist Hospital, Miller Medical, National Association for Continuing Education, Novartis, Paradigm, Pearl, Peer Voice, Pfizer, Prime, Roche, Sunovion, Theravance, Unity Biotechnology, UptoDate, WebMD and Western Society of Allergy and Immunology; nonfinancial support from Annenberg, California Society for Allergy and Immunology, CME Incite, ConCert, Genentech, Janssen, Miller Medical, National Association for Continuing Education, Novartis, Pearl, Pfizer, Roche, Sunovion, Theravance, WebMD and Western Society of Allergy and Immunology; and other support from GlaxoSmithKline and Merio outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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