Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial

Abstract

BackgroundProspective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids.MethodsThe 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to umeclidinium/vilanterol 62.5/25\u2009μg once-daily, umeclidinium 62.5\u2009μg once-daily or salmeterol 50\u2009μg twice-daily. The primary endpoint was trough forced expiratory volume in 1\u2009s (FEV1) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions.ResultsChange from baseline in trough FEV1 at Week 24 was 66\u2009mL (95% confidence interval [CI]: 43, 89) and 141\u2009mL (95% CI: 118, 164) greater with umeclidinium/vilanterol versus umeclidinium and salmeterol, respectively (both p\u2009<\u20090.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs umeclidinium: 0.37 [95% CI: 0.06, 0.68], p\u2009=\u20090.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p\u2009=\u20090.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with umeclidinium (by 16–25% [p\u2009<\u20090.01]) and salmeterol (by 26–41% [p\u2009<\u20090.001]). Safety profiles were similar between treatments.ConclusionsUmeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.