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 journalArticlepeer-review

1 Scopus citations


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 languageAmerican English
Article number107040
JournalRespiratory Medicine
StatePublished - Dec 2022
Externally publishedYes

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


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


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