Abstract
Benefits of triple therapy with a long-acting muscarinic antagonist (LAMA), added to inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA), have been demonstrated. Limited data assessing the efficacy of the LAMA umeclidinium (UMEC) added to ICS/LABA are available. The aim of this study is to evaluate the efficacy and safety of UMEC added to ICS/LABAs in patients with moderate-to-very-severe COPD. This is a multicentre, randomised, double-blind, parallel-group study. Patients were symptomatic (modified Medical Research Council Dyspnoea Scale score ⩾2), despite receiving ICS/LABA (fluticasone propionate/salmeterol (FP/SAL, branded) 500/50 mcg, budesonide/formoterol (BD/FOR, branded) 200/6 mcg or 400/12 mcg, or other ICS/LABAs) ⩾30 days before the run-in (7±2 days). Patients were randomised 1:1 to once-daily UMEC 62.5 mcg or placebo (PBO), added to twice-daily open-label ICS/LABA for 12 weeks. Primary end point was trough forced expiratory volume in 1 s (FEV1) at Day 85; secondary end point was weighted mean (WM) 0–6 h FEV1 at Day 84; other end points included COPD Assessment Test (CAT) score and Transition Dyspnoea Index (TDI) score. Adverse events (AEs) were investigated. In the UMEC+ICS/LABA and PBO+ICS/LABA groups, 119 and 117 patients were randomised, respectively. Patients received FP/SAL (40%), BD/FOR (43%) and other ICS/LABAs (17%). UMEC+ICS/LABA resulted in significant improvements in trough FEV1 (Day 85) and in WM 0–6 h FEV1 (Day 84) versus PBO+ICS/LABA (difference: 123 and 148 ml, respectively, both P<0.001). Change from baseline for UMEC+ICS/LABA versus PBO+ICS/LABA was significantly different for CAT score at Day 84 (−1.31, P<0.05), but not for TDI score (0.40, P=0.152). AE incidence was similar with UMEC+ICS/LABA (38%) and PBO+ICS/LABA (42%). UMEC+ICS/LABA improved lung function and CAT score in patients with symptomatic COPD versus PBO+ICS/LABA (ClinicalTrials.gov NCT02257372).
Highlights
Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow limitation, which contributes significantly to morbidity and mortality, and it presents a significant economic burden worldwide.[1]
UMEC+inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) resulted in statistically significant and clinically meaningful improvements in change from baseline in 0 − 6 h post-dose weighted mean (WM) forced expiratory volume in 1 s (FEV1) at Day 84 compared with PBO+ICS/LABA (148 ml, 95% confidence interval (CI): 99, 197; P o 0.001; Table 2)
Significant and clinically meaningful improvements in the change from baseline in FEV1 were observed at 15 min post dose on Day 84 for UMEC+ICS/LABA compared with PBO+ICS/ LABA (127 ml, 95% CI: 75, 179; P o 0.001)
Summary
Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow limitation, which contributes significantly to morbidity and mortality, and it presents a significant economic burden worldwide.[1]. Significant and clinically meaningful improvements in the change from baseline in FEV1 were observed at 15 min post dose on Day 84 for UMEC+ICS/LABA compared with PBO+ICS/ LABA (127 ml, 95% CI: 75, 179; P o 0.001). In the post hoc subgroup analyses of trough FEV1 by ICS/LABA subgroup, UMEC+FP/SAL 500/50 mcg resulted in a statistically significant improvement in change from baseline in trough FEV1 at Day 85 versus PBO+ FP/SAL 500/50 mcg (156 ml, 95% CI: 77, 235; Po 0.001; n = 42 in each treatment group). The mean improvement in the total SGRQ score with UMEC 62.5 mcg triple therapy compared with ICS/LABA alone was statistically significant at Week 4, but not at Week 12; the magnitude of the treatment effect was similar at both visits and was in line with the other larger UMEC+ICS/LABA studies previously reported.[6]. The improvements observed in this study were not consistent across PRO measures and did not reach reported minimal clinically important differences, possibly because all baseline PROs were measured
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