InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations

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  • Dave Singh
  • Gerard J. Criner
  • Mark T. Dransfield
  • David M.G. Halpin
  • Mei Lan K. Han
  • Lange, Peter
  • Sally Lettis
  • David A. Lipson
  • David Mannino
  • Neil Martin
  • Fernando J. Martinez
  • Bruce E. Miller
  • Robert Wise
  • Chang Qing Zhu
  • David Lomas

Background: Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. Methods: 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). Results: Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile. Conclusions: Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. Trial registration: NCT02164513

TidsskriftRespiratory research
Udgave nummer1
Antal sider14
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This study was funded by GSK (study number CTT116855). The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. The corresponding author had full access to all the data and the final responsibility to submit for publication. Ellipta is owned by or licensed to the GSK group of companies.

Funding Information:
David Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC) and David Lomas by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). David Lomas is an NIHR Senior Investigator. Editorial support in the form of preparation of the first draft based on input from all authors, and collation and incorporation of author feedback to develop subsequent drafts, was provided by Eloise Morecroft and Chrystelle Rasamison, of Fishawack Indicia Ltd, UK, part of Fishawack Health, and was funded by GSK.

Funding Information:
DS reports personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Genentech, Glenmark, Menarini, Mundipharma, Novartis, Peptinnovate, Pfizer, Pulmatrix, Theravance and Verona, and grant support from AstraZeneca, Boehringer Ingelheim, Chiesi, Glenmark, Menarini, Mundipharma, Novartis, Pfizer, Pulmatrix, Theravance and Verona. GC has received personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, CSA Medical, Eolo, GSK, HGE Technologies, Novartis, Nuvaira, Olympus, Pulmonx and Verona. MD has received personal fees from AstraZeneca, Teva, Boehringer Ingelheim and GSK and contracted clinical trial support from AstraZeneca, Boehringer Ingelheim and GSK. DH reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis and Pfizer, and non-financial support Boehringer Ingelheim and Novartis. MH has received personal fees from AstraZeneca, Boehringer Ingelheim, Merck, Mylan and GSK, and research support from Novartis and Sunovion. PL reports personal fees and grant support from GSK, AstraZeneca and Boehringer Ingelheim. SL, DaLi, NM, and C-QZ are GSK employees and hold stock/shares in GSK. DM and BM are former GSK employees and hold stock/shares in GSK. FM has received personal fees and non-financial support from the American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, Chiesi, ConCert, Continuing Education, Genentech, GSK, Inova Fairfax Health System, Miller Communications, National Society for Continuing Education, Novartis, Pearl Pharmaceuticals, PeerView Communications, Potomac, Prime Communications, Puerto Rico Respiratory Society, Roche, Sunovion, Theravance, University of Alabama Birmingham, Physicians Education Resource, Canadian Respiratory Network and Teva, non-financial support from Gilead, Nitto, ProterrixBio and Zambon, personal fees from Columbia University, Integritas, MD magazine, Methodist Hospital Brooklyn, New York University, Unity, UpToDate, WedMD/MedScape, Western Connecticut Health Network, Academic CME, Patara, PlatformIQ, American Thoracic Society, Rockpointe and France Foundation, grant support from NIH, Rare Disease Health Communications and ProMedior, and is a member of steering committees for Afferent/Merck, Biogen, Veracyte, Prometic, Bayer and Bridge Biotherapeutics. RW has been a consultant for Circassia, Pneuma, Verona, Mylan/Theravance, Propeller Health, has received personal fees from AstraZeneca/Medimmune/Pearl, Boehringer Ingelheim, Contrafect, Roche-Genentech, GSK, Merck, AbbVie, ChemRx, Kiniska, Bristol Myers Squibb, Galderma, Kamada, Pulmonx, Kinevant and Puretech, has received research grants from Boehringer Ingelheim, Sanofi-Aventis and GSK. DaLo has received grant income, honoraria, and consultancy fees from GSK, and personal fees from Grifols, and chaired the GSK Respiratory Therapy Area Board 2012–2015.

Publisher Copyright:
© 2021, The Author(s).

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