Dual Bronchodilator Therapy with Umeclidinium/Vilanterol Versus Tiotropium plus Indacaterol in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

Abstract

IntroductionThe fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).MethodsThis 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD. The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin −50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84. Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St. George’s Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.ResultsTrough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) −29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND. The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference −23 mL; 95 % CI −54 to 8 mL). The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores. The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.ConclusionUMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.Trial numbersClinicalTrials.gov study ID NCT02257385; GSK study no. 116961.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-016-0131-2) contains supplementary material, which is available to authorized users.

A Network Meta-Analysis of Long-Acting Muscarinic Antagonist (LAMA) and Long-Acting β2-Agonist (LABA) Combinations in COPD

“…However, a subsequent direct comparison of TIO ? IND with UMEC/VI found no significant difference in rescue medication use [44].…”

Comparative Effectiveness of Long-Acting Beta2-Agonist Combined with a Long-Acting Muscarinic Antagonist or Inhaled Corticosteroid in Chronic Obstructive Pulmonary Disease

“…Clinical trials of the fixed‐dose LABA/LAMAs reported similar or lower frequencies of exacerbations compared with the monotherapy arms . There have been relatively few comparative studies of LABA/LAMA and LABA/ICS efficacy.…”

“…Clinical trials of the fixed-dose LABA/LAMAs reported similar or lower frequencies of exacerbations compared with the monotherapy arms. 19,21,[26][27][28] There have been relatively few comparative studies of LABA/LAMA and LABA/ ICS efficacy. One study compared the lung function of a LABA/LAMA and LABA/ICS in the short term; this was a 6-week randomized trial demonstrating that the 12-hour lung function profiles of patients receiving a combination of tiotropium/formoterol were significantly better than those receiving combination salmeterol/fluticasone (as measured by FEV 1 area under the curve [AUC][0-12], forced vital capacity [FVC] AUC[0-12], peak FEV 1 , and peak FVC).…”

Double bronchodilation in chronic obstructive pulmonary disease: a crude analysis from a systematic review

“…Each combination had undergone a specific development program and clinical trial testing to assess its efficacy and safety for patients with COPD. Unfortunately, no direct head-to-head comparison of the available combinations has been performed yet, the only exception being a clinical trial assessing tiotropium/indacaterol versus UMEC/VIL 7. The results of this study indicated similar improvements in lung function and patient-reported outcomes over a 12-week period, with comparable tolerability and safety profiles 7…”