Efficacy and Safety of Umeclidinium/Vilanterol in Current and Former Smokers with COPD: A Prespecified Analysis of The EMAX Trial

Leif H Bjermer, Isabelle H Boucot, Claus F Vogelmeier, François Maltais, Paul W Jones, Lee Tombs, Chris Compton, David A Lipson, Edward M Kerwin, Leif H Bjermer, Isabelle H Boucot, Claus F Vogelmeier, François Maltais, Paul W Jones, Lee Tombs, Chris Compton, David A Lipson, Edward M Kerwin

Abstract

Introduction: Smoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD.

Methods: The 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS. Current and former smoker subgroups were defined by smoking status at screening.

Results: The analysis included 1203 (50%) current smokers and 1221 (50%) former smokers. Both subgroups demonstrated greater improvements from baseline in trough FEV1 at week 24 (primary endpoint) with umeclidinium/vilanterol versus umeclidinium (least squares [LS] mean difference, mL [95% CI]; current: 84 [50, 117]; former: 49 [18, 80]) and salmeterol (current: 165 [132, 198]; former: 117 [86, 148]) and larger reductions in rescue medication inhalations/day over 24 weeks versus umeclidinium (LS mean difference [95% CI]; current: - 0.42 [- 0.63, - 0.20]; former: - 0.25 - 0.44, - 0.05]) and salmeterol (current: - 0.28 [- 0.49, - 0.06]; former: - 0.29 [- 0.49, - 0.09]). Umeclidinium/vilanterol increased the odds (odds ratio [95% CI]) of clinically significant improvement at week 24 in Transition Dyspnea Index versus umeclidinium (current: 1.54 [1.16, 2.06]; former: 1.32 [0.99, 1.75]) and salmeterol (current: 1.37 (1.03, 1.82]; former: 1.60 [1.20, 2.13]) and Evaluating Respiratory Symptoms-COPD versus umeclidinium (current: 1.54 [1.13, 2.09]; former: 1.50 [1.11, 2.04]) and salmeterol (current: 1.53 [1.13, 2.08]; former: 1.53 [1.12, 2.08]). All treatments were well tolerated in both subgroups.

Conclusions: In current and former smokers, umeclidinium/vilanterol provided greater improvements in lung function and symptoms versus umeclidinium and salmeterol, supporting consideration of dual-bronchodilator therapy in symptomatic patients with COPD regardless of their smoking status.

Trial registration: ClinicalTrials.gov NCT03034915.

Keywords: COPD; LABA; LAMA; Maintenance treatment; Salmeterol; Smoker; Smoking; Umeclidinium; Umeclidinium/vilanterol.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Change from baseline in trough FEV1 at weeks 4, 12, and 24 in A current smokers and B former smokers. CI confidence interval, FEV1 forced expiratory volume in 1 s, LS least squares, MCID minimum clinically important difference, SAL salmeterol, UMEC umeclidinium, VI vilanterol
Fig. 2
Fig. 2
A SAC-TDI focal score and B change from baseline in E-RS total score across all time points in current smokers. CI confidence interval, E-RS Evaluating Respiratory Symptoms–COPD, LS least squares, MCID minimum clinically important difference, SAC-TDI self-administered computerized Transition Dyspnea Index, SAL salmeterol, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium, VI vilanterol
Fig. 3
Fig. 3
A SAC-TDI focal score and B change from baseline in E-RS total score across all time points in former smokers. CI confidence interval, E-RS Evaluating Respiratory Symptoms–COPD, LS least squares, MCID minimum clinically important difference, SAC-TDI self-administered computerized Transition Dyspnea Index, SAL salmeterol, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium, VI vilanterol
Fig. 4
Fig. 4
Proportion of responders for symptoms and health status outcomes in A current smokers and B former smokers. CAT COPD Assessment Test, CI confidence interval, COPD chronic obstructive pulmonary disease, E-RS Evaluating Respiratory Symptoms–COPD, SAC-TDI self-administered computerized Transition Dyspnea Index, SAL salmeterol, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium, VI vilanterol
Fig. 5
Fig. 5
Change from baseline in A rescue medication inhalations/day and B percentage of rescue-free days across all time points in current smokers. CI confidence interval, LS least squares, SAL salmeterol, UMEC umeclidinium, VI vilanterol
Fig. 6
Fig. 6
Change from baseline in A rescue medication inhalations/day and B percentage of rescue-free days across all time points in former smokers. CI confidence interval, LS least squares, SAL salmeterol, UMEC umeclidinium, VI vilanterol
Fig. 7
Fig. 7
Risk of a first CID in A current smokers and B former smokers. an/N number of patients with an event/number of patients with at least one post-baseline assessment (not including exacerbations) for at least one of the individual components or patients who had an exacerbation; bmoderate/severe exacerbation. CAT COPD Assessment Test, CI confidence interval, CID clinically important deterioration, COPD chronic obstructive pulmonary disease, FEV1 trough forced expiratory volume in 1 s, HR hazard ratio, SAC-TDI self-administered computerized Transition Dyspnea Index, SAL salmeterol, SGRQ St George’s Respiratory Questionnaire, UMEC umeclidinium, VI vilanterol

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