P275 Comparing clinically relevant improvement with umeclidinium/vilanterol and tiotropium/olodaterol in symptomatic copd: a randomised non-inferiority crossover trial

Introduction and Objectives Here we report the Results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β 2 -agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg and tiotropium/olodaterol (TIO/OLO) 5/5 mcg in patients with chronic obstructive pulmonary disease (COPD). Methods This randomised, 2-period crossover study (204990, NCT02799784) included inhaled corticosteroid-free patients with COPD, a modified Medical Research Council dyspnoea score ≥2, forced expiratory volume in 1 s (FEV 1 )/forced vital capacity ratio of 1 50%–70% predicted. Patients were randomised to UMEC/VI (62.5/25 mcg once daily) via an ELLIPTA dry powder inhaler followed by TIO/OLO 5/5 mcg (2 puffs once daily) via a RESPIMAT inhaler (each for 8 weeks with an interim 3 week washout period), or vice versa . The primary endpoint was change from baseline (CFB) in trough FEV 1 at Week 8 with a non-inferiority (NI) margin of –50 mL in the per protocol (PP) population. Additional outcomes included inspiratory capacity (IC), rescue medication use and ease of inhaler use (assessed using a six-point questionnaire). Adverse events (AEs) were also assessed. Results 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat (ITT) population and 227 in the PP population. The primary endpoint of CFB in trough FEV 1 at Week 8 confirmed NI of UMEC/VI vs TIO/OLO (175 mL vs 122 mL; least squares mean difference 53 mL [95% confidence interval: 26, 80]; p 1 at Weeks 4 and 8 vs TIO/OLO, and showed significant improvements at Weeks 4 and 8 in IC and rescue medication use (Table). The ELLIPTA inhaler was rated higher than RESPIMAT in all ease-of-use questionnaire items (p≤0.001). The incidence of on-treatment AEs was similar in both groups (UMEC/VI, n=59 [25%]; TIO/OLO, n=71 [31%]). Conclusions In this first, direct, once-daily LAMA/LABA comparison, a greater likelihood of improvements in lung function was demonstrated with UMEC/VI vs TIO/OLO. The ELLIPTA inhaler was preferred to RESPIMAT. Both LAMA/LABAs were well tolerated. Funding GSK (204990 [NCT02799784]) Please refer to page A261 for declarations of interest in relation to abstract P275.