Umeclidinium/Vilanterol Versus Tiotropium/Olodaterol in Maintenance-Naïve Patients with Moderate Symptomatic Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis.

ABSTRACT

INTRODUCTION: Appropriate timing for dual bronchodilator therapy initiation in chronic obstructive pulmonary disease (COPD) management is uncertain. Combination therapy is recommended as step-up from monotherapy or first-line treatment in patients with persistent symptoms. In this setting, umeclidinium/vilanterol (UMEC/VI) demonstrated improved lung function and reduced rescue medication use over tiotropium/olodaterol (TIO/OLO). This subgroup analysis explored efficacy differences between these combinations in patients naïve to COPD maintenance therapy before study entry. METHODS: Post hoc analysis of an 8-week, randomized, open-label, assessor-blind, two-period crossover study (204990; NCT02799784) comparing UMEC/VI 62.5/25 mcg and TIO/OLO 5/5 mcg, focused on maintenance-naïve (MN) patients with moderate COPD and persistent symptoms (modified Medical Research Council dyspnea score ≥ 2). Change from baseline (CFB) in trough forced expiratory volume in 1 s (FEV1), percentage of FEV1 responders (CFB ≥ 100 ml), rescue medication use and safety were evaluated. RESULTS: The MN population comprised 63% of the intent-to-treat (ITT) population (148/236 patients) and had similar baseline demographics. At week 8, adjusted mean (standard error) improvements in trough FEV1 from baseline were clinically meaningful for both combinations (UMEC/VI 167 [17] ml; TIO/OLO 110 [18] ml; adjusted mean difference [95% confidence interval (CI)] 57 [23-92] ml; p = 0.001; %CFB 11 vs. 8%). Proportion of FEV1 responders was greater with UMEC/VI versus TIO/OLO at week 8 (60 vs. 42%; odds ratio [95% CI] 1.90 [1.12-3.22]; p = 0.018). Reduction in rescue medication use was 0.20 (95% CI 0.07-0.34) puffs/day greater with UMEC/VI versus TIO/OLO over weeks 1-8 (p = 0.003). Adverse events incidence was similar (UMEC/VI 24%; TIO/OLO 29%). CONCLUSIONS: These results highlight that the efficacy difference between UMEC/VI and TIO/OLO demonstrated in the ITT population is maintained in MN patients. Greater lung function improvements with UMEC/VI versus TIO/OLO were accompanied by symptom improvements, as reflected in a significantly lower need for supplemental rescue medication. FUNDING: GSK. TRIAL REGISTRATION NCT02799784.