Exploring the Comparative Efficacy and Safety of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol in Moderate Symptomatic COPD: A Randomized Non-Inferiority Crossover Trial

Abstract

SESSION TITLE: Late-Breaking Abstracts SESSION TYPE: Late-Breaking Abstract Slide PRESENTED ON: Wednesday, November 1, 2017 at 02:45 PM - 04:15 PM PURPOSE: In a prior study of long-acting muscarinic antagonist (LAMA) treatment in patients with stable chronic obstructive pulmonary disease (COPD), a significant increase in change from baseline (CFB) in trough forced expiratory volume in 1 second (FEV1) was observed with umeclidinium (UMEC) vs tiotropium (TIO) (53 mL [95% confidence interval {CI}: 25, 81], p<0.001; Feldman G, Int J COPD 2016;11:719-730). We hypothesized that this efficacy difference would also be shown during once-daily fixed-dose combination treatment with the LAMA/long-acting β2-agonist (LABA) combinations UMEC/vilanterol (UMEC/VI) and TIO/olodaterol (TIO/OLO). METHODS: This randomized, open-label, 2-period, crossover study (204990, NCT02799784) recruited inhaled corticosteroid-free COPD patients with a modified Medical Research Council dyspnea score ≥2, FEV1/forced vital capacity ratio <0.70 and post-albuterol FEV1 50-70% predicted. Patients were randomized to receive UMEC/VI (62.5/25 mcg once daily) via an ELLIPTA 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), or vice versa. The primary endpoint was CFB in trough FEV1 at Week 8 with a non-inferiority (NI) margin of -50mL in the per protocol (PP) population. If NI was established, superiority was tested in the intent-to-treat (ITT) population. Rescue medication use and adverse events (AEs) were also assessed. RESULTS: 236 patients (mean age 64.4 years, 60% male) were included in the ITT population (PP population, n=227). The primary endpoint of CFB in trough FEV1 at Week 8 in the PP population confirmed NI of UMEC/VI vs TIO/OLO (175 mL vs 122 mL; least squares [LS] mean difference 53 mL [95% CI: 26, 80]; p<0.001). CFB in trough FEV1 in the ITT population was superior at Week 8 with UMEC/VI (180 mL) vs TIO/OLO (128 mL; LS mean difference 52 mL [95% CI: 28, 77]; p<0.001]). CFB in mean rescue use (puffs/day; Weeks 1-8) favored UMEC/VI over TIO/OLO (-0.94 vs -0.68; 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, statistically significant and clinically meaningful improvements in lung function were observed in patients receiving UMEC/VI vs TIO/OLO. Both LAMA/LABAs were well tolerated. Funding: GSK (204990 [NCT02799784]) CLINICAL IMPLICATIONS: An efficacy gradient exists in the LAMA/LABA class. DISCLOSURE: Ana Sousa: Employee: GSK, Shareholder: Holds stocks and shares in GSK David Lipson: Employee: GSK, Shareholder: Holds stocks and shares in GSK Lee Tombs: Other: Contingent worker contracted by GSK Chris Compton: Employee: GSK, Shareholder: Holds stocks and shares in GSK Bernardino Alcázar Navarrete: Consultant fee, speaker bureau, advisory committee, etc.: GSK, Novartis AG, Boehringer Ingelheim, Chiesi, Laboratorios Menarini, Gebro, AstraZeneca, Other: Non-financial support from: GSK, Novartis AG, Boehringer Ingelheim, Chiesi, Laboratorios Menarini, Grant monies (from industry related sources): Novartis AG, Laboratorios Menarini, Other: Patent: P201730724 The following authors have nothing to disclose: Gregory Feldman No Product/Research Disclosure Information