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

Adv Ther. 2017 Nov;34(11):2518-2533. doi: 10.1007/s12325-017-0626-4. Epub 2017 Nov 1.


Introduction: We 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.

Methods: This 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.

Results: In 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.

Conclusion: In 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 registration: identifier NCT02799784.

Funding: GlaxoSmithKline.

Keywords: Bronchodilation; COPD; LABA; LAMA; Long-acting muscarinic antagonist; Long-acting β2-agonist; Olodaterol; Tiotropium; Umeclidinium; Vilanterol.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Aged
  • Benzoxazines / administration & dosage
  • Benzoxazines / therapeutic use*
  • Benzyl Alcohols / administration & dosage
  • Benzyl Alcohols / therapeutic use*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Chlorobenzenes / administration & dosage
  • Chlorobenzenes / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Nebulizers and Vaporizers
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quinuclidines / administration & dosage
  • Quinuclidines / therapeutic use*
  • Tiotropium Bromide / administration & dosage
  • Tiotropium Bromide / therapeutic use*
  • Treatment Outcome


  • Benzoxazines
  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • Drug Combinations
  • GSK573719
  • Quinuclidines
  • tiotropium-olodaterol
  • vilanterol
  • Tiotropium Bromide

Associated data