Efficacy and safety of umeclidinium/vilanterol in the treatment of chronic obstructive pulmonary disease: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

XIE Xingyue , JIANG Bing ,  MIAO Lili

Department of Respiratory, Yongchuan Hospital of Chongqing Medical University, Yongchuan, 402160, P.R.China;

Corresponding author：

MIAO Lili, Email: Miao-lili@163.com

Keywords：

Umeclidinium/vilanterol; Chronic obstructive pulmonary disease; Efficacy; Safety; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.201706009

Video：

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Objective To systematically review the efficacy and safety of umeclidinium/vilanterol in the treatment of chronic obstructive pulmonary disease. Methods PubMed, The Cochrane Library, WanFang Data, CNKI and VIP databases were electronically searched to collect randomized controlled trials (RCTs) about umeclidinium/vilanterol for chronic obstructive pulmonary disease from inception to March 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results Eight RCTs involving 8 992 patients were included. The results of meta-analysis showed that: (1) umeclidinium/vilanterol vs. placebo: umeclidinium/vilanterol could significantly improve Trough FEV₁ (MD=0.20, 95%CI 0.17 to 0.23, P<0.000 01) and the quality of life: TDI score (MD=0.99, 95%CI 0.71 to 1.28,P<0.000 01), SGRQ score (MD=–4.00, 95%CI –5.35 to –2.66,P<0.000 01), SOBDA score (MD=–0.16, 95%CI –0.23 to –0.09,P<0.000 01), and reduce the use of rescue drugs (salbutamol), while not increase the adverse events. (2) umeclidinium/vilanterolvs. fluticasone propionate/salmeterol: UMEC/VI could improve lung function in patients with COPD: Trough FEV₁ (MD=0.09, 95%CI 0.07 to 0.11, P<0.000 01), reduce the use of rescue drugs (salbutamol), and had lower adverse events. But there was no significant difference in the quality of life between two groups. (3) umeclidinium/vilanterolvs. single bronchodilator: umeclidinium/vilanterol could significantly improve spirometric parameters: Trough FEV₁ (MD=0.08, 95%CI 0.07 to 0.10, P<0.000 01), and the quality of life: TDI score (MD=0.38, 95%CI 0.17 to 0.59,P=0.000 3), SGRQ score (MD=–1.18, 95%CI –2.06 to –0.29, P=0.009). Umeclidinium/vilanterol could significantly reduce the use of rescue drugs (salbutamol) without increasing the adverse events. Conclusion UMEC/VI is superior to placebo in the treatment of COPD patients, which can significantly improve lung function, control symptoms and improve the quality of life, with good safety and tolerance. Compared with salmeterol/fluticacin, UMEC/VI has a significant effect on improving lung function and controlling symptoms without increasing adverse effects, while UMEC/VI is easier to use with better patient compliance. UMEC/VI is superior to bronchodilator alone in improving lung function, controlling symptoms and improving the quality of life without increasing the incidence of adverse events. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.

Citation： XIE Xingyue, JIANG Bing, MIAO Lili. Efficacy and safety of umeclidinium/vilanterol in the treatment of chronic obstructive pulmonary disease: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(12): 1404-1412. doi: 10.7507/1672-2531.201706009 Copy

1.	Vestbo J, Hurd SS, Agustí AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
2.	Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006, 3(11): e442.
3.	Diaz-Guzman E, Mannino DM. Epidemiology and prevalence of chronic obstructive pulmonary disease. Clin Chest Med, 2014, 35(1): 7-16.
4.	Suissa S, Patenaude V, Lapi F, et al. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax, 2013, 68(11): 1029-1036.
5.	Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2014, (3): CD010115.
6.	Corrado A, Rossi A. How far is real life from COPD therapy guidelines? An Italian observational study. Respir Med, 2012, 106(7): 989-997.
7.	Rossi A, Guerriero M, Corrado A, et al. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir Res, 2014, 15: 77.
8.	Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med, 2014, 371(14): 1285-1294.
9.	Vestbo J, Hurd S, Agusti A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
10.	Hu C, Jia J, Dong K, et al. Pharmacokinetics and tolerability of inhaled umeclidinium and vilanterol alone and in combination in healthy Chinese subjects: a randomized, open-label, crossover trial. PLoS One, 2015, 10(3): e121264.
11.	Cazzola M, Molimard M. The scientific rationale for combining long-acting β₂-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther, 2010, 23(4): 257-267.
12.	Meurs H, Dekkers BG, Maarsingh H, et al. Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target. Pulm Pharmacol Ther, 2013, 26(1): 145-155.
13.	Tal-Singer R, Cahn A, Mehta R, et al. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol, 2013, 701(1-3): 40-48.
14.	Kempsford R, Norris V, Siederer S. Vilanterol trifenatate, a novel inhaled long-acting beta 2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD. Pulm Pharmacol Ther, 2013, 26(2): 256-264.
15.	Singh D. New combination bronchodilators for COPD: current evidence and future perspectives. Br J Clin Pharmacol, 2015, 79(5): 695-708.
16.	Nannini LJ, Poole P, Milan SJ, et al. Combined corticosteroid and long-acting beta 2-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2013, (11): CD003794.
17.	Feldman G, Walker RR, Brooks J, et al. 28-Day safety and tolerability of umeclidinium in combination with vilanterol in COPD: a randomized placebo-controlled trial. Pulm Pharmacol Ther, 2012, 25(6): 465-471.
18.	Donohue JF, Maleki-Yazdi MR, Kilbride S, et al. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med, 2013, 107(10): 1538-1546.
19.	Donohue JF, Worsley S, Zhu CQ, et al. Improvements in lung function with umeclidinium/vilanterol versus fluticasone propionate/salmeterol in patients with moderate-to-severe COPD and infrequent exacerbations. Respir Med, 2015, 109(7): 870-881.
20.	Celli B, Crater G, Kilbride S, et al. Once-daily umeclidinium/vilanterol 125/25 mg therapy in COPD a randomized, controlled study. Chest, 2014, 145(5): 981-991.
21.	Decramer M, Anzueto A, Kerwin E, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med, 2014, 2(6): 472-486.
22.	Maleki-Yazdi MR, Kaelin T, Richard N, et al. Efficacy and safety of umeclidinium/vilanterol 62.5/25 mcg and tiotropium 18 mcg in chronic obstructive pulmonary disease: results of a 24-week, randomized, controlled trial. Respir Med, 2014, 108(12): 1752-1760.
23.	François Maltais, Sally S, Alison C, et al. Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials. Ther Adv Respir Dis, 2014, 8(6): 169-181.
24.	Zheng J, Zhong N, Newlands A, et al. Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1753-1767.
25.	Singh D, Worsley S, Zhu CQ, et al. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulm Med, 2015, 15: 91.
26.	McDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med, 2011, 365(17): 1567-1575.
27.	Cohen JS, Miles MC, Donohue JF, et al. Dual therapy strategies for COPD: the scientific rationale for LAMA+LABA. Int J Chron Obstruct Pulmon Dis, 2016, 11: 785-797.
28.	Belmonte KE. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. Proc Am Thorac Soc, 2005, 2(4): 297-304.
29.	Rhoden KJ, Meldrum LA, Barnes P. Inhibition of cholinergic transmission in human airways by B2-receptors. J Appl Physiol, 1988, 65: 700-707.
30.	Mehta R, Hardes K, Cahn A, et al. Safety, tolerability and pharmacokinetics (PK) of repeated doses of GSK573719 Inhalation Powder, a new long-acting muscarinic antagonist, in healthy adults. Eur Respir J, 2011, 38: 3972.
31.	Mehta R, Hardes K, Brealey N, et al. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, non-randomized study. Int J Chron Obstruct Pulmon Dis, 2015, 10: 15-23.
32.	Horita N, Miyazawa N, Tomaru K, et al. Long-acting muscarinic antagonist+long-acting beta agonist versus long-acting beta agonist+inhaled corticosteroid for COPD: A systematic review and meta-analysis. Respirology, 2015, 20(8): 1153-1159.

1. Vestbo J, Hurd SS, Agustí AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006, 3(11): e442.
3. Diaz-Guzman E, Mannino DM. Epidemiology and prevalence of chronic obstructive pulmonary disease. Clin Chest Med, 2014, 35(1): 7-16.
4. Suissa S, Patenaude V, Lapi F, et al. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax, 2013, 68(11): 1029-1036.
5. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2014, (3): CD010115.
6. Corrado A, Rossi A. How far is real life from COPD therapy guidelines? An Italian observational study. Respir Med, 2012, 106(7): 989-997.
7. Rossi A, Guerriero M, Corrado A, et al. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir Res, 2014, 15: 77.
8. Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med, 2014, 371(14): 1285-1294.
9. Vestbo J, Hurd S, Agusti A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
10. Hu C, Jia J, Dong K, et al. Pharmacokinetics and tolerability of inhaled umeclidinium and vilanterol alone and in combination in healthy Chinese subjects: a randomized, open-label, crossover trial. PLoS One, 2015, 10(3): e121264.
11. Cazzola M, Molimard M. The scientific rationale for combining long-acting β₂-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther, 2010, 23(4): 257-267.
12. Meurs H, Dekkers BG, Maarsingh H, et al. Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target. Pulm Pharmacol Ther, 2013, 26(1): 145-155.
13. Tal-Singer R, Cahn A, Mehta R, et al. Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol, 2013, 701(1-3): 40-48.
14. Kempsford R, Norris V, Siederer S. Vilanterol trifenatate, a novel inhaled long-acting beta 2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD. Pulm Pharmacol Ther, 2013, 26(2): 256-264.
15. Singh D. New combination bronchodilators for COPD: current evidence and future perspectives. Br J Clin Pharmacol, 2015, 79(5): 695-708.
16. Nannini LJ, Poole P, Milan SJ, et al. Combined corticosteroid and long-acting beta 2-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2013, (11): CD003794.
17. Feldman G, Walker RR, Brooks J, et al. 28-Day safety and tolerability of umeclidinium in combination with vilanterol in COPD: a randomized placebo-controlled trial. Pulm Pharmacol Ther, 2012, 25(6): 465-471.
18. Donohue JF, Maleki-Yazdi MR, Kilbride S, et al. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med, 2013, 107(10): 1538-1546.
19. Donohue JF, Worsley S, Zhu CQ, et al. Improvements in lung function with umeclidinium/vilanterol versus fluticasone propionate/salmeterol in patients with moderate-to-severe COPD and infrequent exacerbations. Respir Med, 2015, 109(7): 870-881.
20. Celli B, Crater G, Kilbride S, et al. Once-daily umeclidinium/vilanterol 125/25 mg therapy in COPD a randomized, controlled study. Chest, 2014, 145(5): 981-991.
21. Decramer M, Anzueto A, Kerwin E, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med, 2014, 2(6): 472-486.
22. Maleki-Yazdi MR, Kaelin T, Richard N, et al. Efficacy and safety of umeclidinium/vilanterol 62.5/25 mcg and tiotropium 18 mcg in chronic obstructive pulmonary disease: results of a 24-week, randomized, controlled trial. Respir Med, 2014, 108(12): 1752-1760.
23. François Maltais, Sally S, Alison C, et al. Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials. Ther Adv Respir Dis, 2014, 8(6): 169-181.
24. Zheng J, Zhong N, Newlands A, et al. Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study. Int J Chron Obstruct Pulmon Dis, 2015, 10: 1753-1767.
25. Singh D, Worsley S, Zhu CQ, et al. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulm Med, 2015, 15: 91.
26. McDonough JE, Yuan R, Suzuki M, et al. Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med, 2011, 365(17): 1567-1575.
27. Cohen JS, Miles MC, Donohue JF, et al. Dual therapy strategies for COPD: the scientific rationale for LAMA+LABA. Int J Chron Obstruct Pulmon Dis, 2016, 11: 785-797.
28. Belmonte KE. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. Proc Am Thorac Soc, 2005, 2(4): 297-304.
29. Rhoden KJ, Meldrum LA, Barnes P. Inhibition of cholinergic transmission in human airways by B2-receptors. J Appl Physiol, 1988, 65: 700-707.
30. Mehta R, Hardes K, Cahn A, et al. Safety, tolerability and pharmacokinetics (PK) of repeated doses of GSK573719 Inhalation Powder, a new long-acting muscarinic antagonist, in healthy adults. Eur Respir J, 2011, 38: 3972.
31. Mehta R, Hardes K, Brealey N, et al. Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, non-randomized study. Int J Chron Obstruct Pulmon Dis, 2015, 10: 15-23.
32. Horita N, Miyazawa N, Tomaru K, et al. Long-acting muscarinic antagonist+long-acting beta agonist versus long-acting beta agonist+inhaled corticosteroid for COPD: A systematic review and meta-analysis. Respirology, 2015, 20(8): 1153-1159.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of umeclidinium/vilanterol in the treatment of chronic obstructive pulmonary disease: a meta-analysis

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