LABA/LAMA联合治疗中到极重度COPD有效性和安全性的网状Meta分析  

Efficacy and Safety of LABA/LAMA in the Treatment of Moderate to Extremely Severe COPD: a Network Meta Analysis

作　　者：户光 刘梓晗 魏玉娜 李灿 曾明 Hu Guang;Liu Zihan;Wei Yuna;Li Can;Zeng Ming(CIS Technology Service Co.Ltd.,Beijing 100028,China;Department of Pharmacology,the Seventh Medical Center of PLA ARMY General Hospital)

机构地区：[1]中公网医疗信息技术有限公司,北京100028 [2]中国人民解放军总医院第七医学中心药理科

出　　处：《药物流行病学杂志》2020年第1期3-15,共13页Chinese Journal of Pharmacoepidemiology

摘　　要：目的:采用网状Meta分析方法系统评价长效β2受体激动药(LABA)/长效抗胆碱能拮抗药(LAMA)联合治疗中到极重度慢性阻塞性肺疾病(COPD)的有效性及安全性。方法:计算机检索PubMed、Embase、Cochrane Central Register of Controlled Trials(CENTRAL)、ClinicalTrail.gov、SinoMed、CNKI、WanFang Data数据库,搜集LABA/LAMA联合治疗中到极重度COPD的随机对照试验(RCT),检索时限均为建库至2018年7月。由两名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 14软件在频率学框架下进行数据处理分析。结果:纳入35个RCT,共31 758例患者,包括11种干预措施。网状Meta分析结果显示:格隆溴铵/茚达特罗(50/110μg)[MD=0.255,95%CI(0.181,0.329)]、格隆溴铵/茚达特罗(15.6/27.5μg)[MD=0.223,95%CI(0.195,0.252)]、噻托溴铵/茚达特罗[MD=0.209,95%CI(0.166,0.252)]对FEV1谷值的改善均优于其他干预措施;格隆溴铵/茚达特罗(50/110μg)[MD=-4.719,95%CI(-6.161,-3.278)]、格隆溴铵/茚达特罗(15.6/27.5μg)[MD=-4.928,95%CI(-6.783,-3.073)]、噻托溴铵/奥达特罗[MD=-4.202,95%CI(-5.387,-3.016)]能明显降低圣乔治呼吸问卷(SGRQ)评分;格隆溴铵/茚达特罗(50/110μg)、噻托溴铵/奥达特罗、格隆溴铵/福莫特罗、芜地溴铵/维兰特罗、噻托溴铵治疗的患者急性加重发生率均低于安慰剂,差异有统计学意义,LABA/LAMA联合组间的差异均无统计学意义;各干预措施安全性相当,各组间严重药品不良反应发生率的差异无统计学意义;噻托溴铵/奥达特罗组患者依从性较好,退出率低于噻托溴铵、格隆溴铵/茚达特罗(50/110μg)、格隆溴铵/福莫特罗、芜地溴铵/维兰特罗治疗组,差异有统计学意义。结论:格隆溴铵/茚达特罗(15.6/27.5μg)、噻托溴铵/奥达特罗相对其他LABA/LAMA联合治疗措施对中到极重度COPD有更好的临床疗效和依从性。Objective:To systematically evaluate the efficacy and safety of LABA/LAMA in the treatment of moderate to extremely severe chronic obstructive pulmonary disease(COPD) by means of Network Meta analysis. Methods:PubMed, Embase, Cochrane Central Register of Controlled Trials(CENTRAL), ClinicalTrail.gov, SinoMed, CNKI and WanFang Data were electronically searched to collect randomized controlled trial(RCTs) about LABA/LAMA for the treatment of moderate to extremely severe COPD from inception to July 2, 2018. Two reviewers independently screened literatures, extracted data and assessed the risk of bias of included studies. Then, analysis was performed using Stata 14 software within frequentist framework. Results:Thirty-five RCTs involving 31 758 patients were included, including 11 intervention measures. The results of the Network Meta analysis showed that the intervention measures including QVA149(110/50 μg, 27.5/15.6 μg)(MD=0.255, 95%CI 0.181 to 0.329),(MD=0.223, 95%CI 0.195 to 0.252), TIO/IND(MD=0.209, 95%CI 0.166 to 0.252) were superior to other interventions in trough FEV1. The intervention measures of QVA149(110/50 μg, 27.5/15.6 μg)(MD=-4.719, 95%CI-6.161 to-3.278),(MD=-4.928, 95%CI-6.783 to-3.073) and TIO/OLO(MD=-4.202, 95%CI-5.387 to-3.016) reduced the SGRQ score significantly. For the acute exacerbation of COPD patients, the incidence of QVA149(110/50 μg), TIO/OLO, GP/FF, UMEC/VI and TIO was lower than that of placebo, and the difference was statistically significant, there was no statistical difference between the LABA/LAMA combined groups. For severe adverse reaction events, there was no significant difference between the intervention measures. The adherence of TIO/OLO intervention was relatively good, and its withdrawal rate was lower than TIO, QVA149(110/50 μg), GP/FF, UMEC/VI, and the difference was statistically significant. Conclusion:QVA149(27.5/15.6 μg) and TIO/OLO have better clinical efficacy and compliance for COPD.

关 键 词：长效β2受体激动药 长效抗胆碱能拮抗药 联合治疗 慢性阻塞性肺疾病 网状Meta分析 随机对照试验 

分 类 号：R974.3[医药卫生—药品]