A Meta-analysis On The Efficacy And Safety Of Indacaterol/Glycopyrronium For The Treatment Of COPD

Background: Indacaterol/glycopyrronium bromide(QVA149)is a combination of long-acting ?2 agonist and long-acting muscarinic antagonist.Inhaled bronchodilator is currently recommended drug for treating Chronic Obstructive Pulmonary Disease(COPD).LABA/LAMA takes an important position in the treatment of Chronic Obstructive Pulmonary Disease according to COPD guideline(GOLD,2017).Objective: This paper evaluates efficacy and safety of QVA149 compared with placebo?glycopyrronium?tiotropium and Salmeterol/fluticasone(SFC)in patients with moderate to severe COPD by meta-analysis.Methods: Through computer we searched on MEDLINE(Pubmed)?EMBASE(Ovid)?SCOPUS and Cochrane Central Register of Controlled Trials(CENTRAL),and also searched from the following websites: http://www.novctrd.com/ctrd Web App/clinicaltrialrepository/public/login.jsp and https://clinicaltrials.gov/ website.We searched the relevant literatures about QVA149 and identified the required clinical trials according to the inclusion criteria and the exclusion criteria.The data was extracted and analyzed through stata14.0.Results: A total of 11036 patients from 10 randomized controlled trials were included in the meta-analysis.The results showed that QVA149 had a significant increase than placebo in FEV1 [SMD=0.800,95% CI(0.469,1.132),P<0.0001] and TDI [SMD=0.426,95%CI(0.201,0.651),P<0.0001].These meant QVA149 could better improve lung function and symptoms than placebo.There was no significant difference in adverse events?serious adverse events and withdrawals due to adverse events(P=0.141?0.394?0.455 respectively).Compared with glycopyrronium,there was a significant increase in FEV1 [SMD=0.352,95%CI(0.200,0.504),P<0.0001],and a decrease in SGRQ [SMD=-0.098,95%CI(-0.185,-0.011),P=0.027].There were more benefits on percentage of days without rescue therapy use(change from baseline of)[SMD=0.224,95%CI(0.141,0.307),P<0.0001] and change in mean daily use(number of puffs)of rescue therapy [SMD=-0.281,95%CI(-0.364,-0.198),P<0.0001].The outcomes above suggested that QVA149 could better reduce the acute exacerbation of COPD than glycopyrronium.There was no significant difference on adverse events?serious adverse events ?withdrawals due to adverse events(P=0.458?0.352?0.309 respectively).Compared with tiotropium,QVA149 had a significant increase through FEV1 [SMD=0.398,95%CI(0.079,0.717),P=0.014 ]?FVC [SMD=0.148,95% CI(0.034,0.262),P=0.011]?TDI [SMD=0.165,95%CI(0.056,0.273),P=0.003],and a decrease in SGRQ [SMD=-0.145,95%CI(-0.231,-0.059),P=0.001].These results suggested QVA149 was better than tiotropium bromide on efficacy.There was no significant difference on adverse events(P=0.093)and serious adverse events(P=0.492).There was a significant increase through FVC [SMD=0.301,95%CI(0.181,0.420),P<0.0001] when compared with SFC.Adverse events and serious adverse events had no significant difference(P=0.151,0.089 respectively).Conclusions: The efficacy of QVA149 was better than placebo?glycopyrronium ?tiotropium and SFC for the treatment of COPD,while the rate of adverse events did not increase.