不同剂量的雷芬那辛治疗中重度慢性阻塞性肺疾病稳定期有效性及安全性的meta分析

Efficacy and safety of multiple doses of Revefenacin for therapy in patients with moderate to severe chronic obstructive pulmonary disease in stable period: a meta-analysis

关键词:  雷芬那辛  慢性阻塞性肺病  疗效  安全性  meta分析

Key words:  revefenacin  chronic obstructive pulmonary disease(COPD)  efficacy  safety  meta-analysis

摘要:

目的 系统评价多种剂量(22，44，88，175，350，700μg)的雷芬那辛治疗中重度慢性阻塞性肺病(chronic obstructive pulmonary disease，COPD)稳定期的疗效和安全性。方法 计算机检索英文数据库Medline/PubMed、Cochrane图书馆、Embase、Web of science以及维普网、中国知网、万方数据库。同时查阅ClinicalTrials.gov以获取还未发表的试验数据。收集雷芬那辛作为试验组，对照组为安慰剂的用于治疗中度或重度COPD稳定期的随机对照试验(randomized controlled trials，RCTs)，检索时间为从建库至2020年6月。符合纳入标准的临床研究行资料提取，Cochrane系统评价员手册5.1.0偏倚风险工具进行质量评价，RevMan 5.3统计软件行meta分析。结果 共纳入5个RCTs，1927例患者。Meta分析结果显示，雷芬那辛组患者在FEV1改变值[总效应：MD=0.11，95%CI(0.09，0.13)，P<0.00001；22μg：MD=0.05，95%CI(0.00，0.10)，P=0.04；44μg：MD=0.05，95%CI(0.01，0.10)，P=0.01；88μg：MD=0.12，95%CI(0.07，0.18)，P<0.00001；175μg：MD=0.13，95%CI(0.11，0.16)，P<0.00001；350μg：MD=0.1，95%CI(0.05，0.20)，P=0.0007；700μg：MD=0.08，95%CI(0.03，0.13)，P=0.002]，和SGQR得分降低4个或者更多单位的患者比例[总效应：RR=1.29，95%CI(1.12，1.49)，P=0.0004；88μg：RR=1.29，95%CI(1.06，1.58)，P=0.01；175μg：RR=1.29，95%CI(1.06，1.58)，P=0.01]方面均优于安慰剂组，差异有统计学意义。雷芬那辛组呼吸困难发生率显著性低于安慰剂组(P=0.005)，背痛发生率则显著性高于安慰剂组(P=0.006)；在88μg与175μg直接比较中，两者在总不良反应发生率、严重不良反应发生率以及某些其他常见不良反应(头痛、咳嗽、背痛、咽喉痛、呼吸困难、上呼吸道感染)与安慰剂相比差异均无显著性差异。结论 雷芬那辛对中重度COPD稳定期患者显示出较好的疗效和耐受性，175μg与88μg相比，可能在治疗各方面无显著差异，88μg与175μg或许都能成为临床治疗中重度COPD稳定期的可选方案。

Abstract:

OBJECTIVE To systematically evaluate the efficacy and safety of multiple doses of revefenacin(22, 44, 88, 175, 350, 700 μg) in patients with moderate to severe chronic obstructive pulmonary disease(COPD) in stable period.METHODS literature searching was performed via Medline/PubMed, Cochrane Library, Embase, Web of Science, VIP, CNKI, WanFang databases from their inception to June 2020, and searched ClinicalTrials.gov to obtain unpublished data. The randomized controlled trials(RCTs) compared efficacy and safety of revefenacin versus placebo in patients with moderate to severe COPD in stable period were included. The risk of bias was assessed via Cochrane risk of bias assessment tool after data extracted from clinical studies which met the inclusion criteria and the meta-analysis was performed by using RevMan 5.3 software.RESULTS Five RCTs with 1 927 participates were enrolled. The meta-anlysis showed that revefenacin was superior to placebo in terms of change in FEV1[total: MD=0.11, 95%CI(0.09, 0.13), P<0.000 01; 22 μg: MD=0.05, 95%CI(0.00, 0.10), P=0.04; 44 μg: MD=0.05, 95%CI(0.01, 0.10), P=0.01; 88 μg: MD=0.12, 95%CI(0.07, 0.18)，P<0.000 01; 175 μg: MD=0.13, 95%CI(0.11, 0.16), P<0.000 01; 350 μg: MD=0.1, 95%CI(0.05, 0.20), P=0.000 7; 700 μg: MD=0.08, 95%CI(0.03, 0.13), P=0.002] and the proportion of patients whose SGQR scores dropped by four or more units[total: RR=1.29, 95%CI(1.12, 1.49), P=0.000 4; 88 μg: RR=1.29, 95%CI(1.06,1.58), P=0.01; 175 μg: RR=1.29, 95%CI(1.06, 1.58), P=0.01] with a significant difference. The incidence of dyspnea in Revefenain group was significantly lower than that in placebo group(P=0.005), and the incidence of back pain was significantly higher than that in placebo group(P=0.006). In a direct comparison between 88 μg and 175 μg, there was no significant difference in the incidence of total adverse reactions, serious adverse events, and common adverse events(headache, cough, back pain, sore throat, dyspnea, upper respiratory tract infection) compared with placebo.CONCLUSION Revefenacin shows better efficacy and tolerance in patients with moderate to severe COPD in stable period, and 175 μg did not exhibit its advantage over 88 μg, both 88 μg and 175 μg may become alternative options for the clinical treatment of moderate to severe COPD in stable period.