Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis

Samuel Bardsley; Gerard J. Criner; David M.G. Halpin; Mei Lan K. Han; Nicola A. Hanania; David Hill; Peter Lange; David A. Lipson; Fernando J. Martinez; Dawn Midwinter; Thomas M. Siler; Dave Singh; Robert A. Wise; Richard N. van Zyl-Smit; Neville Berkman

doi:10.1016/j.rmed.2022.107040

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis

Samuel Bardsley, Gerard J. Criner, David M.G. Halpin, Mei Lan K. Han, Nicola A. Hanania, David Hill, Peter Lange, David A. Lipson, Fernando J. Martinez, Dawn Midwinter, Thomas M. Siler, Dave Singh, Robert A. Wise, Richard N. van Zyl-Smit, Neville Berkman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: Smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status. Methods: IMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed. Results: Of the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77–0.95]; P = 0.003 and 0.86 [0.76–0.98]; P = 0.021) and former smokers (0.85 [0.78–0.91]; P < 0.001 and 0.70 [0.64–0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers. Conclusions: FF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers. Clinical trial registration: GSK (CTT116855/NCT02164513).

Original language	American English
Article number	107040
Journal	Respiratory Medicine
Volume	205
DOIs	https://doi.org/10.1016/j.rmed.2022.107040
State	Published - Dec 2022
Externally published	Yes

Bibliographical note

Funding Information:
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 Alexandra Berry, PhD, of Fishawack Indicia Ltd., UK, part of Fishawack Health and was funded by GSK. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC) . ELLIPTA is owned by or licensed to the GSK Group of Companies.

Funding Information:
This work was funded by GSK (study number CTT116855 ; NCT02164513 ). The funders of the study had a role in the study design, data analysis, data interpretation and writing of the report.

Publisher Copyright:
© 2022 The Authors

Keywords

Health-related quality of life
Lung function
Single-inhaler triple therapy
Smoking
Symptoms

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10.1016/j.rmed.2022.107040

Cite this

Bardsley, S., Criner, G. J., Halpin, D. M. G., Han, M. L. K., Hanania, N. A., Hill, D., Lange, P., Lipson, D. A., Martinez, F. J., Midwinter, D., Siler, T. M., Singh, D., Wise, R. A., van Zyl-Smit, R. N., & Berkman, N. (2022). Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis. Respiratory Medicine, 205, Article 107040. https://doi.org/10.1016/j.rmed.2022.107040

@article{a99745d405de46d3abe0546824613427,

title = "Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis",

abstract = "Background: Smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status. Methods: IMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed. Results: Of the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77–0.95]; P = 0.003 and 0.86 [0.76–0.98]; P = 0.021) and former smokers (0.85 [0.78–0.91]; P < 0.001 and 0.70 [0.64–0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers. Conclusions: FF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers. Clinical trial registration: GSK (CTT116855/NCT02164513).",

keywords = "Health-related quality of life, Lung function, Single-inhaler triple therapy, Smoking, Symptoms",

author = "Samuel Bardsley and Criner, {Gerard J.} and Halpin, {David M.G.} and Han, {Mei Lan K.} and Hanania, {Nicola A.} and David Hill and Peter Lange and Lipson, {David A.} and Martinez, {Fernando J.} and Dawn Midwinter and Siler, {Thomas M.} and Dave Singh and Wise, {Robert A.} and {van Zyl-Smit}, {Richard N.} and Neville Berkman",

note = "Funding Information: 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 Alexandra Berry, PhD, of Fishawack Indicia Ltd., UK, part of Fishawack Health and was funded by GSK. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC) . ELLIPTA is owned by or licensed to the GSK Group of Companies. Funding Information: This work was funded by GSK (study number CTT116855 ; NCT02164513 ). The funders of the study had a role in the study design, data analysis, data interpretation and writing of the report. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = dec,

doi = "10.1016/j.rmed.2022.107040",

language = "American English",

volume = "205",

journal = "Respiratory Medicine",

issn = "0954-6111",

publisher = "W.B. Saunders Ltd",

}

Bardsley, S, Criner, GJ, Halpin, DMG, Han, MLK, Hanania, NA, Hill, D, Lange, P, Lipson, DA, Martinez, FJ, Midwinter, D, Siler, TM, Singh, D, Wise, RA, van Zyl-Smit, RN & Berkman, N 2022, 'Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis', Respiratory Medicine, vol. 205, 107040. https://doi.org/10.1016/j.rmed.2022.107040

TY - JOUR

T1 - Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD

T2 - IMPACT trial post hoc analysis

AU - Bardsley, Samuel

AU - Criner, Gerard J.

AU - Halpin, David M.G.

AU - Han, Mei Lan K.

AU - Hanania, Nicola A.

AU - Hill, David

AU - Lange, Peter

AU - Lipson, David A.

AU - Martinez, Fernando J.

AU - Midwinter, Dawn

AU - Siler, Thomas M.

AU - Singh, Dave

AU - Wise, Robert A.

AU - van Zyl-Smit, Richard N.

AU - Berkman, Neville

N1 - Funding Information: 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 Alexandra Berry, PhD, of Fishawack Indicia Ltd., UK, part of Fishawack Health and was funded by GSK. Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC) . ELLIPTA is owned by or licensed to the GSK Group of Companies. Funding Information: This work was funded by GSK (study number CTT116855 ; NCT02164513 ). The funders of the study had a role in the study design, data analysis, data interpretation and writing of the report. Publisher Copyright: © 2022 The Authors

PY - 2022/12

Y1 - 2022/12

N2 - Background: Smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status. Methods: IMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed. Results: Of the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77–0.95]; P = 0.003 and 0.86 [0.76–0.98]; P = 0.021) and former smokers (0.85 [0.78–0.91]; P < 0.001 and 0.70 [0.64–0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers. Conclusions: FF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers. Clinical trial registration: GSK (CTT116855/NCT02164513).

AB - Background: Smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). In IMPACT, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy significantly reduced moderate/severe exacerbation rates and improved lung function and health status versus FF/VI or UMEC/VI in COPD patients. This post hoc analysis investigated trial outcomes by smoking status. Methods: IMPACT was a double-blind, 52-week trial. Patients aged ≥40 years with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. Endpoints assessed by smoking status at screening included rate and risk of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George's Respiratory Questionnaire total score at Week 52. Safety was also assessed. Results: Of the 10,355 patients in the intent-to-treat population, 3,587 (35%) were current smokers. FF/UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in current (rate ratio 0.85 [95% confidence interval: 0.77–0.95]; P = 0.003 and 0.86 [0.76–0.98]; P = 0.021) and former smokers (0.85 [0.78–0.91]; P < 0.001 and 0.70 [0.64–0.77]; P < 0.001). FF/UMEC/VI significantly reduced time-to-first on-treatment moderate/severe exacerbation versus FF/VI and UMEC/VI in former smokers, and versus FF/VI in current smokers. Similar trends were seen for lung function and health status. Former smokers receiving inhaled corticosteroid-containing therapy had higher pneumonia incidence than current smokers. Conclusions: FF/UMEC/VI improved clinical outcomes versus dual therapy regardless of smoking status. Benefits of FF/UMEC/VI versus UMEC/VI were greatest in former smokers, potentially due to relative corticosteroid resistance in current smokers. Clinical trial registration: GSK (CTT116855/NCT02164513).

KW - Health-related quality of life

KW - Lung function

KW - Single-inhaler triple therapy

KW - Smoking

KW - Symptoms

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U2 - 10.1016/j.rmed.2022.107040

DO - 10.1016/j.rmed.2022.107040

M3 - Article

C2 - 36470149

AN - SCOPUS:85143550081

SN - 0954-6111

VL - 205

JO - Respiratory Medicine

JF - Respiratory Medicine

M1 - 107040

ER -

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis

Abstract

Bibliographical note

Keywords

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