Meta Analysis About The Difference Of Clinical Benefit Between LABA/LAMA/ICS Triple Therapy And LABA/LAMA Or LABA/ICS Double Therapy In Patients With Stable Chronic Obstructive Pulmonary Disease

Background:Chronic Obstructive Pulmonary Disease（COPD）is a disease characterized by persistent airflow restriction that can be prevented and treated.Currently,the triple inhaled therapy of LABA/LAMA/ICS and the dual inhaled therapy of LABA/ICS and LABA/LAMA are playing an important role in the treatment of patients with stable COPD.Recent evidence-based research suggest that for patients with COPD,especially patients with moderately severe COPD,triple therapy significantly reduces the risks of acute exacerbation occurs and the SGRQ scores,and can more effectively improve the pulmonary function,compared with LABA/ICS and LABA/LAMA treatment.However,in the past two years,new research results have been published,and there is still inconsistency of endpoints in previous studies.It is necessary to make new meta-analysis.Objective:In this paper,we use meta-analysis as a tool to evaluate the differences between the LABA/LAMA/ICS treatment group and the LABA/LAMA or LABA/ICS treatment group in the risk of acute exacerbation,pulmonary function changes,clinical symptoms and the occurrence of adverse events in stable COPD patients,in order to further clarify the feasibility and necessity of triple therapy.Methods:We use computer to search for the literature from Pub Med,Embase,Cochrane Library and Ciinicalt Tial.gov.Literature related to LABA/LAMA/ICS studies was searched,and required clinical studies were identified according to the established inclusion and exclusion criteria.The included clinical studies were evaluated for literature quality and data extraction,and data analysis was performed by using STATA16.0.For the dichotomous variables,the effect size of lgarithm of RR or the lgarithm of OR value is combined statistics,and the 95%confidence interval is described.For continuous variables,the effect size of SMD was combined statistics,and the 95%confidence interval was described.Results:A total of 24763 stable COPD patients were enrolled in 9 randomized controlled trials.Results of a meta-analysis showed that the triple therapy had a significantly lower risk of moderate-to-severe acute exacerbation（lg RR=-0.21,95%CI:-0.28～-0.16）than any of the dual therapy.In addition,the triple therapy was more effective than the dual therapy in reducing the number of emergency medications used per day（SMD=-0.25,95%CI:-0.35～-0.15）.Meanwhile,compared with all types of dual therapy,patients receiving triple therapy have a higher measure of FEV₁（SMD=80.85ml,95%CI:48.59～113.11）.Triple therapy had a lower SGRQ score（SMD=-1.71,95%CI:-2.11～-1.31）than dual drug therapy.The risk of severe adverse effects of triple therapy was similar to that of dual therapy（lg OR=0,95%CI:-0.06～0.06）.For the risk of pneumonia,it is shown that the triple regimen had a similar risk of pneumonia（lg OR=-0.04,95%CI:-0.12～0.04）compared with LABA/ICS therapy,while the triple therapy had a higher risk of pneumonia（lg OR=0.23,95%CI:0.01～0.46）than the LABA/LAMA therapy.Conclusion:The triple therapy was more effective in reducing the risk of acute exacerbations,reducing the use of emergency medications,improving lung function,and relieving patients’symptoms than the dual therap.In terms of drug safety,the triple therapy shows a similar risk of severe adverse events compared with the dual therapy,although the triple regimen was associated with a higher risk of pneumonia than the LABA/LAMA regimen.