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

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

doi:10.1186/s12931-021-01706-y

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

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

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	130
Tidsskrift	Respiratory Research
Vol/bind	22
Udgave nummer	1
Sider (fra-til)	130
ISSN	1465-9921
DOI	https://doi.org/10.1186/s12931-021-01706-y
Status	Udgivet - 28 apr. 2021

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10.1186/s12931-021-01706-y

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Singh, D., Criner, G. J., Dransfield, M. T., Halpin, D. M. G., Han, M. K., Lange, P., Lettis, S., Lipson, D. A., Mannino, D., Martin, N., Martinez, F. J., Miller, B. E., Wise, R., Zhu, C.-Q., & Lomas, D. (2021). InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations. Respiratory Research, 22(1), 130. Artikel 130. https://doi.org/10.1186/s12931-021-01706-y

Singh, D, Criner, GJ, Dransfield, MT, Halpin, DMG, Han, MK, Lange, P, Lettis, S, Lipson, DA, Mannino, D, Martin, N, Martinez, FJ, Miller, BE, Wise, R, Zhu, C-Q & Lomas, D 2021, 'InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations', Respiratory Research, bind 22, nr. 1, 130, s. 130. https://doi.org/10.1186/s12931-021-01706-y

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

abstract = "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.",

keywords = "Aged, Biomarkers/blood, Bronchodilator Agents/therapeutic use, Disease Progression, Double-Blind Method, Drug Combinations, Female, Fibrinogen/metabolism, Humans, Lung/drug effects, Male, Middle Aged, Predictive Value of Tests, Pulmonary Disease, Chronic Obstructive/blood, Severity of Illness Index, Time Factors, Treatment Outcome, Up-Regulation",

author = "Dave Singh and Criner, {Gerard J} and Dransfield, {Mark T} and Halpin, {David M G} and Han, {MeiLan K} and Peter Lange and Sally Lettis and Lipson, {David A} and David Mannino and Neil Martin and Martinez, {Fernando J} and Miller, {Bruce E} and Robert Wise and Chang-Qing Zhu and David Lomas",

year = "2021",

month = apr,

day = "28",

doi = "10.1186/s12931-021-01706-y",

language = "English",

volume = "22",

pages = "130",

journal = "Respiratory Research",

issn = "1465-9921",

publisher = "BioMed Central Ltd",

number = "1",

}

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, MeiLan 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

PY - 2021/4/28

Y1 - 2021/4/28

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.TRIAL REGISTRATION: NCT02164513.

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.TRIAL REGISTRATION: NCT02164513.

KW - Aged

KW - Biomarkers/blood

KW - Bronchodilator Agents/therapeutic use

KW - Disease Progression

KW - Double-Blind Method

KW - Drug Combinations

KW - Female

KW - Fibrinogen/metabolism

KW - Humans

KW - Lung/drug effects

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Pulmonary Disease, Chronic Obstructive/blood

KW - Severity of Illness Index

KW - Time Factors

KW - Treatment Outcome

KW - Up-Regulation

UR - http://www.scopus.com/inward/record.url?scp=85104982803&partnerID=8YFLogxK

U2 - 10.1186/s12931-021-01706-y

DO - 10.1186/s12931-021-01706-y

M3 - Journal article

C2 - 33910578

SN - 1465-9921

VL - 22

SP - 130

JO - Respiratory Research

JF - Respiratory Research

IS - 1

M1 - 130

ER -

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

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