Efficacy and safety of the dual bronchodilator combination umeclidinium/vilanterol in COPD by age and airflow limitation severity: A pooled post hoc analysis of seven clinical trials.

Abstract

BACKGROUND\nElderly patients with chronic obstructive pulmonary disease (COPD) and those with more severe airway limitation are perceived to experience reduced efficacy from inhaled bronchodilators, especially those administered in a dry powder inhaler. This study compared the efficacy and safety of a long-acting muscarinic antagonist/long-acting β2-agonist dry powder combination in elderly patients with COPD and patients with moderate-to-very severe airflow limitation.\n\n\nMETHODS\nThis post hoc pooled analysis of seven randomized studies of ≥12 weeks duration investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25\u202fμg versus tiotropium (TIO) 18\u202fμg or fluticasone propionate/salmeterol (FP/SAL) 250/50\u202fμg. Change from baseline in trough forced expiratory volume in 1\u202fs (FEV1), a common efficacy measure in all trials, proportion of FEV1 responders (≥100\u202fmL increase from baseline) and safety outcomes were analyzed at Day 28, 56, and 84 in patients classified by age (<65, ≥65, and ≥75 years of age) and severity of baseline airflow limitation (Global initiative for chronic Obstructive Lung Disease [GOLD] stage 2 [moderate] and stage 3/4 [severe/very severe]). A 24-week analysis was also conducted for the UMEC/VI versus TIO comparison.\n\n\nRESULTS\nThe pooled intent-to-treat population comprised 3821 patients (≥65 years: 44-45%; ≥75 years: 9-10%; GOLD stage 3/4: 50-55%); 2246, 874, and 701 patients received UMEC/VI, TIO, or FP/SAL, respectively. Significant improvements in trough FEV1 at Day 84 were observed with UMEC/VI versus TIO or FP/SAL irrespective of age (all p\u202f≤\u202f0.029) or GOLD stage (all p\u202f<\u202f0.001). The proportion of FEV1 responders at Day 84 was significantly greater with UMEC/VI versus TIO or FP/SAL across all age groups (all p\u202f≤\u202f0.016) and GOLD stages (all p\u202f<\u202f0.001). Safety profiles were similar between treatment groups.\n\n\nCONCLUSION\nUMEC/VI consistently demonstrated improved lung function versus TIO and FP/SAL across age and airflow limitation severity subgroups, with no safety concerns, indicating that UMEC/VI provides no loss in efficacy or additional safety concerns for both elderly patients with COPD and patients with severe/very severe airway limitation.