6种药物预防遗传性血管性水肿急性发作有效性及安全性的网状Meta分析

Efficacy and safety of six drugs for preventing acute attack of hereditary angioedema:a network meta-analysis

目的综合评价拉那利尤单抗(lanadelumab)、阿伏司他(avoralstat)、贝罗司他(berotralstat)、加达西单抗(garadacimab)、多尼达洛森(donidalorsen)和血源性C1酯酶抑制剂(pdC1-INH)6种药物预防遗传性血管性水肿(HAE)急性发作的有效性及安全性。方法检索PubMed、Cochrane Library、Embase、Web of Science、中国知网、万方和维普从建库到2024年1月所有关于上述6种药物预防HAE急性发作的文献,在Stata 17.0和R 4.3.2软件中进行网状Meta分析。结果共纳入10项随机对照试验,HAE患者619例。网状Meta分析结果显示,在减少患者每4周HAE发作次数方面,有5种药物与安慰剂比较有显著差异(P<0.05),累积排序概率显示加达西单抗疗效最佳(MD=2.59,95%CI:1.38~3.79);在不良事件发生率与严重不良事件发生率方面,所有治疗药物与安慰剂相比无显著差异(P>0.05);累积排序概率显示拉那利尤单抗不良事件发生率最低,多尼达洛森严重不良事件发生率最低。结论预防HAE急性发作的6种药物中,加达西单抗疗效最好,拉那利尤单抗安全性较好。

AIM To synthesize the available clinical evidence to evaluate the efficacy and safety of lanadelumab,avoralstat,berotralstat,garadacimab,donidalorsen and plasma-derived C1-esterase inhibitor for preventing the acute attack of hereditary angioedema(HAE)using network meta-analysis.METHODS PubMed,Cochrane Library,Embase,Web of Science,CNKI,Wanfang,and VIP databases were searched for randomized controlled trials that evaluated the efficacy and safety of these six drugs in the prevention of the acute attack of HAE from the establishment of the library to January 2024.A network meta-analysis(NMA)was performed by Stata 17.0 and R 4.3.2.RESULTS A total of 10 randomized controlled trials fulfilling the inclusion criteria were retrieved,including 619 patients.NMA showed that five kinds of drugs were superior to placebo in reducing the number of acute HAE attacks every 4 weeks(P<0.05).The surface under the cumulative ranking sorting results showed that garadacimab was the most efficacious(MD=2.59,95%CI:1.38 to 3.79).For the comparison between placebo and these drugs,there were no significant differences in the incidence of adverse events and serious adverse events.The SUCRA indicated that lanadelumab had the lowest incidence of adverse events and donidalorsen had the lowest incidence of serious adverse events.CONCLUSION Garadacimab is the most effective drug of all these firstline agents used to prevent acute attacks of HAE,while lanadelumab has better safety.