Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study

Abstract

IntroductionWe report the results 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 COPD.MethodsThis was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (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 end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of − 50 mL in the per-protocol (PP) population. The incidence of adverse events was also assessed.ResultsIn total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population. UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to 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.ConclusionIn this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD. Both treatments had similar safety profiles. These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.Trial RegistrationClinicalTrials.gov identifier NCT02799784.FundingGlaxoSmithKline.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0626-4) contains supplementary material, which is available to authorized users.

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

“…This was a post hoc analysis of an 8-week, multicenter, randomized, open-label, two-period crossover study (NCT02799784; GSK clinical study identifier 204990) conducted in centers across Germany, Spain, UK, and the USA between July 2016 and April 2017 [21]. The objective of the current analysis was to evaluate the efficacy and safety of UMEC/VI versus TIO/ OLO in an unexpectedly large subgroup of patients who were initiated on a COPD maintenance therapy at randomization.…”

“…Eligibility criteria for enrollment in the study have been previously reported [21]. In brief, patients were C 40 years of age with a diagnosis of COPD in accordance with the American Thoracic Society/European Respiratory Society (ATS/ERS) definition [29]; current or former smokers with a smoking history of C 10 packyears; had a pre-and post-bronchodilator FEV 1 /forced vital capacity (FVC) ratio \ 0.70 and a post-bronchodilator FEV 1 B 70% and C 50% of predicted normal values at enrollment (visit 1) [30]; and had a score of C 2 on the modified Medical Research Council Dyspnea Scale (mMRC) [31].…”

“…The study endpoints have been described previously [21]. The endpoints evaluated in this post hoc analysis were change from baseline (CFB) in trough FEV 1 (ml and ratio to baseline) at weeks 4 and 8, the proportion of responders at weeks 4 and 8 (defined as FEV 1 CFB C 100 ml), CFB in trough FVC and inspiratory capacity (IC) at weeks 4 and 8 (derived using spirometry), use of rescue albuterol over weeks 1-8 (puffs per day) captured using an eDiary, change from baseline in COPD Assessment Test (CAT) score and CAT response rate (C 2 units decrease in CAT score from baseline) [33] at weeks 4 and 8, and CFB in daily respiratory symptoms using the Evaluating Respiratory Symptoms-COPD (E-RS COPD ) scale (weeks 1-8) [34,35].…”

“…While there is increasing evidence of an efficacy gradient within the LAMA and LAMA/LABA classes with respect to lung function [15,[21][22][23], the comparative efficacy of different dual bronchodilator combinations used as first-line therapy has not been studied in appropriately symptomatic patients [24]. The LAMA/LABA combinations umeclidinium/vilanterol (UMEC/ VI) 62.5/25 mcg, delivered via the ELLIPTA dry powder inhaler, and tiotropium/olodaterol (TIO/OLO) 5/5 mcg, delivered via the Respimat soft mist inhaler, are the only LAMA/LABA combinations approved in the USA, Europe and other parts of the world as once-daily maintenance therapies for COPD [25][26][27][28].…”

“…The LAMA/LABA combinations umeclidinium/vilanterol (UMEC/ VI) 62.5/25 mcg, delivered via the ELLIPTA dry powder inhaler, and tiotropium/olodaterol (TIO/OLO) 5/5 mcg, delivered via the Respimat soft mist inhaler, are the only LAMA/LABA combinations approved in the USA, Europe and other parts of the world as once-daily maintenance therapies for COPD [25][26][27][28]. The first direct comparison of these once-daily fixed-dose combinations, in an 8-week crossover study in patients with moderate COPD and persistent symptoms of dyspnea, demonstrated the superiority of UMEC/VI over TIO/OLO for the primary endpoint of trough forced expiratory volume in 1 s (FEV 1 ) [21].…”