5种单克隆抗体预防视神经脊髓炎谱系疾病复发的有效性网状Meta分析及安全性评价

Efficacy and safety of five monoclonal antibodies in preventing relapse of neuromyelitis optica spectrum disorders:network meta-analysis

目的间接比较利妥昔单抗、托珠单抗、依库珠单抗、伊奈利珠单抗及萨特利珠单抗预防视神经脊髓炎谱系疾病复发的有效性并评价其安全性,为临床用药提供参考。方法计算机检索Embase、Medline、PubMed、中国知网和临床试验注册数据库ClinicalTrials.gov、UMIN Clinical Trials Registry、中国临床试验注册中心,收集5种单克隆抗体(试验组)对比安慰剂或其他治疗方案(对照组)的随机对照试验,检索时限为各数据库建库起至2022年4月。由2位研究者独立筛选文献、提取资料,并采用Cochrane风险偏倚评估工具对纳入文献的质量进行评价;采用OpenBUGS软件进行网状Meta分析。安全性方面,对报告中试验组与对照组不良事件发生情况的差异进行χ^(2)检验。结果共纳入7项随机对照试验,涉及793例患者。各指标的累积排序概率曲线下面积(SUCRA)排序结果显示,在降低复发风险方面,依库珠单抗>利妥昔单抗>伊奈利珠单抗>萨特利珠单抗;在降低年复发率方面,依库珠单抗>萨特利珠单抗;在改善残疾进展方面,依库珠单抗>萨特利珠单抗>伊奈利珠单抗>利妥昔单抗>托珠单抗。安全性评方面的χ^(2)检验结果显示,各项研究总体不良事件及严重不良事件的发生风险与对照组比较,差异均无统计学意义(P>0.05),但利妥昔单抗组患者输液反应、恶心呕吐及依库珠单抗组患者上呼吸道感染发生率显著高于安慰剂组(P<0.05)。结论依库珠单抗在上述3种结局指标上的效果均为最优;在改善残疾进展方面,依库珠单抗、萨特利珠单抗及伊奈利珠单抗效果优于其他2种药物;安全性方面,部分不同分级及单项不良事件存在显著性差异,但未发现其与已有的文献及药品说明书的报告结果不一致。

OBJECTIVE To indirectly compare and evaluate the efficacy and safety of rituximab,tocilizumab,eculizumab,inebilizumab and satralizumab in preventing the relapse of neuromyelitis optica spectrum disorders,so as to provide reference for clinical drug use.METHODS Retrieved from Embase,Medline,PubMed,CNKI,ClinicalTrials.gov,UMIN Clinical Trials Registry and Chinese Clinical Trial Registry,randomized controlled trials(RCTs)about five monoclonal antibodies(trial group)versus placebo or other therapeutic scheme(control group)were collected during the inception to Apr.2022.Two reviewers independently screened literature,extracted data,and assessed the quality of included literature with Cochrane risk bias assessment tool.OpenBUGS software was used for network meta-analysis.In terms of safety,Chi-square test was performed for adverse events(AEs)in trial group and control group.RESULTS A total of 7 RCTs were included,involving 793 patients.The results of surface under the cumulative ranking curve(SUCRA)showed the order of capabilities decreasing relapse risk was:eculizumab>rituximab>inebilizumab>satralizumab;the order of capabilities reducing the annual recurrence rate was:eculizumab>satralizumab;the order of capabilities improving the progress of disability was:eculizumab>satralizumab>inebilizumab>rituximab>tocilizumab.In terms of safety,the results ofχ^(2) test showed that there were no statistically significant differences in the risk of total AEs and serious AEs in each study between trial groups and control groups(P>0.05);the incidence of infusion reaction,nausea and vomiting in rituximab group,and that of upper respiratory tract infection in eculizumab group were significantly higher than placebo group(P<0.05).CONCLUSIONS The effect of eculizumab is more optimal in three outcomes;in terms of improving the progress of disability,eculizumab,satralizumab and inebilizumab are more effective than the other two drugs;in terms of safety,there are significant differences in some AEs with different grades and individual AEs,but it is not found that they are inconsistent with the reported results of the existing literature and drug instructions.