TY - JOUR
T1 - InforMing the PAthway of COPD Treatment (IMPACT) trial
T2 - fibrinogen levels predict risk of moderate or severe exacerbations
AU - Singh, Dave
AU - Criner, Gerard J.
AU - Dransfield, Mark T.
AU - Halpin, David M.G.
AU - Han, Mei Lan K.
AU - Lange, Peter
AU - Lettis, Sally
AU - Lipson, David A.
AU - Mannino, David
AU - Martin, Neil
AU - Martinez, Fernando J.
AU - Miller, Bruce E.
AU - Wise, Robert
AU - Zhu, Chang Qing
AU - Lomas, David
N1 - 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.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - COPD
KW - COPD exacerbations
KW - Fibrinogen
KW - Pharmacotherapy
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U2 - 10.1186/s12931-021-01706-y
DO - 10.1186/s12931-021-01706-y
M3 - Article
C2 - 33910578
AN - SCOPUS:85104982803
SN - 1465-9921
VL - 22
JO - Respiratory research
JF - Respiratory research
IS - 1
M1 - 130
ER -