Efficacy of Umeclidinium/Vilanterol in Elderly Patients with COPD: A Pooled Analysis of Randomized Controlled Trials

Abstract

ObjectiveThe aim of this pooled analysis was to assess the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 µg dual bronchodilation versus placebo in elderly symptomatic patients with chronic obstructive pulmonary disease (COPD).MethodsWe conducted a post hoc pooled analysis of data from 10 randomized controlled trials (RCTs). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), proportion of FEV1 responders (≥ 100-mL increase from baseline), and safety were analyzed in patients aged < 65, ≥ 65, and ≥ 75 years on Days 28, 56, and 84 (12-week analysis of parallel-group design studies), Days 28, 56, 84, 112, 140, 168, and 169 (24-week analysis of parallel-group design studies), and Days 2, 42, and 84 (12-week analysis of crossover design studies).ResultsThe UMEC/VI intent-to-treat (ITT) populations comprised 2246, 1296, and 472 patients in the 12-week parallel-group, 24-week parallel-group, and 12-week crossover analysis, respectively (≥ 65 years: 36–44%; ≥ 75 years: 7–11%). The placebo ITT populations comprised 528, 280, and 505 patients, respectively (≥ 65 years: 37–41%; ≥ 75 years: 5–11%). Significant improvements in trough FEV1 and significantly greater proportions of FEV1 responders were seen with UMEC/VI compared with placebo in all analyses regardless of patient age or timepoint considered (p ≤ 0.023), except Day 84 trough FEV1 CFB in the 12-week crossover analysis in patients aged ≥ 75 years (p = 0.064). UMEC/VI safety profile was similar to placebo in all age groups.ConclusionsIn this pooled analysis of RCT data, once-daily UMEC/VI was well tolerated and provided clinically significant lung function benefits compared with placebo in younger and older patients with COPD.FundingGlaxoSmithKline (study 208125).Electronic supplementary materialThe online version of this article (10.1007/s40266-018-0558-y) contains supplementary material, which is available to authorized users.

Effect of Age on Efficacy and Safety of Fluticasone Furoate/Vilanterol (FF/VI), Umeclidinium (UMEC), and UMEC + FF/VI in Patients with Chronic Obstructive Pulmonary Disease: Analyses of Five Randomized Clinical Trials

“…It is noteworthy that a similar trend was observed in previous analyses of UMEC/VI versus placebo in older patients with COPD. 11 However, the lower odds of a FEV 1 response with UMEC + FF/VI versus placebo + FF/VI in the ≥65 years of age subgroup compared with the <65 years of age subgroup do not support this finding. This raises the possibility that bronchodilator monotherapy (LAMA) or dual therapy (LAMA/LABA) may be more appropriate treatment options than ICS/LABA in elderly symptomatic patients at low exacerbation risk, where the goal of treatment is to improve lung function and reduce symptoms; however, further studies are required to confirm this observation and further investigate the effect of age on the efficacy of MITT and single-inhaler triple therapy.…”

“…9,10 Previous post hoc analyses have evaluated the fixeddose combination long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) umeclidinium (UMEC)/vilanterol (VI) in older patients. 11 Consistent and significantly improved lung function compared with placebo was observed in older patients (≥65 and ≥75 years of age) with symptomatic COPD, with no notable diminution of the effect with advanced age. Furthermore, the safety profile for UMEC/VI was comparable in all age groups.…”

“…Concerns have been raised about the use of DPIs in older patients because the ability to generate adequate inspiratory flow may be reduced in these patients. 6 , 11 In this study, all treatments were delivered using the ELLIPTA DPI, a device that has demonstrated consistency of delivered dose and fine particle mass fraction at flows of between 30 L/min and 90 L/min. 21 , 22 Patients with COPD and a FEV 1 <30% predicted have demonstrated the ability to generate peak inspiratory flows of at least 41.6─52 L/min.…”

Pharmacology and Therapeutics of Bronchodilators Revisited

“…At least as far as we can understand from studies with vilanterol/umeclidinium, the LABA/LAMA combinations are effective in elderly patients, improving lung function in a clinically important manner regardless of age (Ray et al, 2018). Furthermore, age does not influence the safety profile of vilanterol/umeclidinium.…”

<p>Evidence-based review of data on the combination inhaler umeclidinium/vilanterol in patients with COPD</p>

“…Several reviews have summarized older clinical data on the dry-powder inhaled a fixed dose of UMEC/VI in COPD treatment 35–37. Similarly, a pooled analysis of older data of elderly patients with COPD showed efficacy of UMEC/VI in this group 38. The earliest studies (see Table 2) included several trials that explored both 62.5 and 125 µg doses of UMEC combined with a 25 µg dose of VI once-a-day in COPD patients 23,39–41.…”