度普利尤单抗治疗支气管哮喘疗效和安全性的meta分析

doi:10.3969/j.issn.1004-583X.2023.10.001

摘要/Abstract

摘要： 目的系统评价度普利尤单抗治疗支气管哮喘的临床疗效和安全性。方法检索中国期刊全文数据库(CNKI)、万方数据库(Wanfang Database)、维普数据库(VIP)、中国生物医学文献数据库(CBM)、Cochrane Library、PubMed、Embase、Web of Science等数据库,检索时间为建库至2023年2月20日,纳入度普利尤单抗治疗支气管哮喘患者的随机对照试验(RCT),使用RevMan5.4软件进行Meta分析。结果总纳入11项RCTs,共3759例患者,Meta分析结果显示,试验组哮喘急性加重人数[RR=0.48, 95%CI (0.40, 0.57), P<0.01]、哮喘控制问卷评分(Asthma control questionnaire, ACQ)[MD =-0.32, 95%CI (-0.43, -0.21), P<0.01]均少于对照组,试验组第1秒用力呼气容积(Forced expiratory volume in 1s, FEV₁)[MD =0.51, 95%CI (0.31, 0.71), P<0.01]、哮喘生活质量问卷评分(Asthma quality of life questionnaire, AQLQ)[MD =0.32, 95%CI (0.20, 0.44), P<0.01]均高于对照组,差异有统计学意义(P<0.05);在血液嗜酸性粒细胞数<300/μl的哮喘人数[RR=1.10, 95%CI (0.93, 1.31), P=0.26]、不良事件[RR=1.03, 95%CI (0.98, 1.08), P=0.22]、严重不良事件[RR=1.21, 95%CI (0.86, 1.71), P=0.28]等方面,两组基本一致,差异无统计学意义(P>0.05)。结论度普利尤单抗可有效减少哮喘急性加重人数、改善肺功能和提高患者的生活质量,且有较好的安全性。

关键词: 度普利尤单抗, 支气管哮喘, Meta分析, 随机对照试验

Abstract: Objective To systematically evaluate the efficacy and safety of dupilumab on the treatment of bronchial asthma. Methods Randomized controlled trials (RCTs) reporting the treatment of dupilumab for bronchial asthma published from database establishment to February 20 in 2023 were systematically searched in CNKI, Wanfang Database, VIP, Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Embase and Web of Science. Meta-analysis was performed by RevMan5.4 software. Results A total of 11 RCTs involving 3759 bronchial asthma patients were enrolled. Meta-analysis results showed that the number of patients with acute exacerbation of asthma (RR=0.48, 95%CI: 0.40, 0.57, P<0.01) and the Asthma Control Questionnaire (ACQ) score (MD=-0.32, 95%CI: -0.43, -0.21, P<0.01) were significantly lower in the experimental group than those of control group. The forced expiratory volume in 1s (FEV₁, MD=0.51, 95% CI: 0.31,0.71, P<0.01) and the Asthma Quality of Life Questionnaire (AQLQ) score (MD=0.32, 95%CI: 0.20, 0.44, P<0.01) were significantly higher than those of the control group. There were no significant differences in the number of bronchial asthma patients with blood eosinophil count <300/μl (RR=1.10, 95%CI: 0.93, 1.31, P=0.26), incidence of adverse events (RR=1.03, 95%CI: 0.98,1.08, P=0.22) and incidence of serious adverse events (RR=1.21, 95%CI: 0.86, 1.71, P=0.28) between groups (P>0.05). Conclusion Dupilumab can decrease the number of asthma exacerbations, improve pulmonary function and quality of life with a high safety.

Key words: dupilumab, bronchial asthma, Meta-analysis, randomized controlled trial

中图分类号:

R562.25

阮俊文, 周建荣, 刘惟优, 袁小亮, 颜颢. 度普利尤单抗治疗支气管哮喘疗效和安全性的meta分析[J]. 临床荟萃, 2023, 38(10): 869-877.

Ruan Junwen, Zhou Jianrong, Liu Weiyou, Yuan Xiaoliang, Yan Hao. Meta-analysis of the efficacy and safety of dupilumab on the treatment of bronchial asthma[J]. Clinical Focus, 2023, 38(10): 869-877.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.10.001

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I10/869

图/表 14

图1 文献筛选流程图

Fig.1 Flow chart of literature screening

表1 纳入研究的基本特征

Tab.1 Basic characteristics of included studies

纳入研究	病例数	平均年龄(岁)		干预措施		疗程	结局指标
纳入研究	T/C	T	C	T	C	疗程	结局指标
Bacharier 2021^[11]	273/135	8.9±1.6	9.0±1.6	达必妥100 mg q2w(W≤30kg), 200 mg q2w(W>30kg)	安慰剂q2w	52w	①②③④⑥⑦
Busse(a) 2018^[12]	634/317	≥12		达必妥200 mg q2w	安慰剂q2w	52w	②
Busse(b) 2018^[12]	634/317	≥12		达必妥300 mg q2w	安慰剂q2w	52w	②
Domingo 2022^[13]	103/107	52.9±12.6	50.3±12.6	达必妥300 mg q2w	安慰剂q2w	24w	①②④⑥
Rabe 2018^[9]	103/107	51.9±12.5	50.7±12.8	达必妥300 mg q2w	安慰剂q2w	24w	①②③⑥⑦
Wechsler 2021^[14]	75/74	51.3±12.7	47.0±11.4	达必妥300 mg q2w	安慰剂q2w	12w	①②③④⑤⑥⑦
Wenzel(a) 2016^[15]	150/158	48.6±13.0		达必妥200 mg q2w	安慰剂q2w	24w	①②④⑤⑥⑦
Wenzel(b) 2016^[15]	154/158	48.6±13.0		达必妥200 mg q4w	安慰剂q4w	24w	①②④⑤⑥⑦
Wenzel(c) 2016^[15]	157/158	48.6±13.0		达必妥300 mg q2w	安慰剂q2w	24w	①②④⑤⑥⑦
Wenzel(d) 2016^[15]	157/158	48.6±13.0		达必妥300 mg q4w	安慰剂q4w	24w	①②④⑤⑥⑦
Wenzel 2013^[16]	52/52	37.8±13.2	41.6±13.1	达必妥300 mg qw	安慰剂qw	12w	①④⑥⑦

图2 偏倚风险图

Fig.2 Chart of risk of bias

图3 偏倚风险概要

Fig.3 Summary of risk of bias

图4 哮喘急性加重人数的meta分析森林图

Fig.4 Forest plots of the number of acute exacerbations of asthma

图5 FEV1的meta分析森林图

Fig.5 Forest plots of FEV1

图6 血液嗜酸性粒细胞数<300/μl的哮喘人数的meta分析森林图

Fig.6 Forest plots of the number of bronchial asthma patients with blood eosinophil count <300/μl

图7 ACQ的meta分析森林图

Fig.7 Forest plots of ACQ

图8 AQLQ的meta分析森林图

Fig.8 Forest plots of AQLQ

图9 不良事件的meta分析森林图

Fig.9 Forest plots of adverse event

图10 严重不良事件的meta分析森林图

Fig.10 Forest plots of serious adverse event

图11 统计学异质性分析图注:“急性加重”为“哮喘急性加重人数”;“嗜酸粒”为“血液嗜酸性粒细胞数<300/μl的哮喘人数”

Fig.11 Analytical graph of statistical heterogeneity

图12 统计学意义分析图注:“P<0.00001”取值为“P=0.00001”;在“FEV1”、“AQLQ”、“严重不良事件”中,均存在两项相同大权重研究,在去掉两项相同大权重研究后,所得P值为“0.0006/0.0007”、“<0.0001/<0.00001”、“0.44/0.63”,图中P取值为“0.0007”、“<0.0001”、“0.44”

Fig.12 Analytical graph of statistical significance

图13 FEV1漏斗图

Fig.13 Funnel plot of FEV1

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