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; MeiLan 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

Respir Med. 2022 Dec:205:107040. doi: 10.1016/j.rmed.2022.107040. Epub 2022 Nov 11.

Authors

Affiliations

¹ GSK, Stevenage, UK.
² Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
³ University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK.
⁴ University of Michigan, Pulmonary & Critical Care, Ann Arbor, MI, USA.
⁵ Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA.
⁶ Waterbury Pulmonary Associates, Waterbury, CT, USA.
⁷ Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; Medical Department, Pulmonary Section, Herlev-Gentofte Hospital, Herlev, Denmark.
⁸ GSK, Collegeville, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁹ New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA.
¹⁰ GSK, Brentford, UK.
¹¹ Midwest Chest Consultants, PC, St Charles, MO, USA.
¹² Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester University NHS Foundation Hospital Trust, Manchester, UK.
¹³ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴ Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹⁵ Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address: Neville@hadassah.org.il.

PMID: 36470149
DOI: 10.1016/j.rmed.2022.107040

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.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Inhalation
Adrenal Cortex Hormones / adverse effects
Androstadienes / adverse effects
Benzyl Alcohols / therapeutic use
Bronchodilator Agents* / therapeutic use
Chlorobenzenes / therapeutic use
Double-Blind Method
Drug Combinations
Fluticasone
Humans
Pulmonary Disease, Chronic Obstructive* / diagnosis
Pulmonary Disease, Chronic Obstructive* / drug therapy
Pulmonary Disease, Chronic Obstructive* / epidemiology
Quinuclidines / adverse effects

Substances

Bronchodilator Agents
Androstadienes
vilanterol
Chlorobenzenes
Benzyl Alcohols
Quinuclidines
Fluticasone
Adrenal Cortex Hormones
Drug Combinations

Associated data

ClinicalTrials.gov/NCT02164513