Feldman GJ, et al. - The purpose of this study was to report the outcomes of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with chronic obstructive pulmonary disease (COPD). In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary endpoint of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD. They noted that both treatments had similar safety profiles. These outcomes affirm the results of previous indirect LAMA/LABA comparisons and demonstrate that an effectiveness gradient exists within the LAMA/LABA class.

Methods

• For this research, they designed a randomized, two-period crossover open-label study.
• This study was conducted in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy.
• Patients were randomized to receive UMEC/VI (62.5/25 μg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 μg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa.
• The primary endpoint was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of -50 mL in the per-protocol (PP) population.
• They also evaluated the incidence of adverse events.

Results

• In total, 236 patients (mean age 64.4 years, 60% male) were incorporated into the intent-to-treat population and 227 were incorporated into the PP population.
• UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment regarding trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001].
• Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14).
• Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.