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Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study.
Adv Ther 2017; 34(11):2518-2533AT

Abstract

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

ClinicalTrials.gov identifier NCT02799784.

FUNDING

GlaxoSmithKline.

Authors+Show Affiliations

S. Carolina Pharmaceutical Research, Spartanburg, SC, USA. gfeld3232@aol.com.Respiratory Research and Development, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, UK.Respiratory Research and Development, GlaxoSmithKline, King of Prussia, PA, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Precise Approach Ltd, Birmingham, West Midlands, UK.Global Respiratory Franchise, GlaxoSmithKline, Brentford, Middlesex, UK.Respiratory Therapy Area Unit, GlaxoSmithKline Medicines Research Centre, GlaxoSmithKline, Stevenage, Hertfordshire, UK.Global Respiratory Franchise, GlaxoSmithKline, Brentford, Middlesex, UK.Respiratory Medicine, GlaxoSmithKline, Brentford, Middlesex, UK.Global Respiratory Franchise, GlaxoSmithKline, Brentford, Middlesex, UK.Neumología, Hospital de Alta Resolución de Loja, Granada, Spain.

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

29094315

Citation

Feldman, Gregory J., et al. "Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: a Randomized Study." Advances in Therapy, vol. 34, no. 11, 2017, pp. 2518-2533.
Feldman GJ, Sousa AR, Lipson DA, et al. Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study. Adv Ther. 2017;34(11):2518-2533.
Feldman, G. J., Sousa, A. R., Lipson, D. A., Tombs, L., Barnes, N., Riley, J. H., ... Alcázar Navarrete, B. (2017). Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study. Advances in Therapy, 34(11), pp. 2518-2533. doi:10.1007/s12325-017-0626-4.
Feldman GJ, et al. Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: a Randomized Study. Adv Ther. 2017;34(11):2518-2533. PubMed PMID: 29094315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study. AU - Feldman,Gregory J, AU - Sousa,Ana R, AU - Lipson,David A, AU - Tombs,Lee, AU - Barnes,Neil, AU - Riley,John H, AU - Patel,Sadhana, AU - Naya,Ian, AU - Compton,Chris, AU - Alcázar Navarrete,Bernardino, Y1 - 2017/11/01/ PY - 2017/08/24/received PY - 2017/11/3/pubmed PY - 2018/5/22/medline PY - 2017/11/3/entrez KW - Bronchodilation KW - COPD KW - LABA KW - LAMA KW - Long-acting muscarinic antagonist KW - Long-acting β2-agonist KW - Olodaterol KW - Tiotropium KW - Umeclidinium KW - Vilanterol SP - 2518 EP - 2533 JF - Advances in therapy JO - Adv Ther VL - 34 IS - 11 N2 - 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: ClinicalTrials.gov identifier NCT02799784. FUNDING: GlaxoSmithKline. SN - 1865-8652 UR - https://www.unboundmedicine.com/medline/citation/29094315/Comparative_Efficacy_of_Once_Daily_Umeclidinium/Vilanterol_and_Tiotropium/Olodaterol_Therapy_in_Symptomatic_Chronic_Obstructive_Pulmonary_Disease:_A_Randomized_Study_ L2 - https://dx.doi.org/10.1007/s12325-017-0626-4 DB - PRIME DP - Unbound Medicine ER -