芦可替尼治疗激素难治性移植物抗宿主病有效性和安全性的meta分析

Efficacy and safety of ruxolitinib in the treatment of steroid-refractory graft-versus-host disease:a meta-analysis

目的:系统评价芦可替尼治疗激素难治性移植物抗宿主病的疗效和安全性。方法:计算机检索PubMed、Embase、Cochrane图书馆及ClinicalTrials.gov英文数据库、中国期刊全文数据库(CNKI)、维普和万方数据库,检索截至日期2020年8月。根据研究特点对纳入研究进行质量评价后采用R软件进行统计分析。结果:最终纳入21篇文献,共609例患者。Meta分析结果显示,芦可替尼治疗激素难治性移植物抗宿主病患者的有效率(ORR)为79%(95%CI 72%~85%),完全缓解率(CR)为29%(95%CI 19%~42%),部分缓解率(PR)为46%(95%CI 37%~56%)。其中,急性移植物抗宿主病的ORR为76%(95%CI 67%~82%),CR率为33%(95%CI 24%~45%),PR率为42%(95%CI 34%~49%);慢性移植物抗宿主病的ORR为81%(95%CI 70%~89%),CR率为26%(95%CI 11%~49%),PR率为51%(95%CI 34%~67%)。在安全性方面,使用芦可替尼后骨髓抑制、巨细胞病毒再激活及其他感染的不良反应率增加,血细胞减少发生率为17%(95%CI 10%~28%),巨细胞病毒再激活率为21%(95%CI 15%~29%),其他感染发生率为18%(95%CI 9%~33%)。结论:芦可替尼用于成人急性GVHD和慢性GVHD患者的挽救性治疗,可获得较高的有效率,需关注骨髓抑制和感染的发生。

Objective:To systematically evaluate the efficacy and safety of ruxolitinib in patients with steroid-refractory graft-versus-host disease(SR-GVHD).Methods:The database including PubMed,Embase,Cochrane Library,ClinicalTrials.gov in English,CNKI,CBM,VIP and Wanfang were searched,and the references of the included studies were retrieved manually,with the retrieval time from inception to August 2020.The quality evaluation of included criteria based on the characteristics of the literature was evaluated,and the meta-analysis was conducted by using R version3.5 software.Results:A total of 21 studies involving 609 patients were included.The results of meta-analysis showed that the overall response rate(ORR),complete remission(CR)rate and partial remission(PR)rate of ruxolitinib in the treatment of SR-GVHD were 79%(95%CI 72%-85%),29%(95%CI 19%-42%),46%(95%CI 37%-56%),respectively.For patients with SR-aGVHD,the ORR,CR rate and PR rate were 76%(95%CI 67%-82%),33%(95%CI 24%-45%)and 42%(95%CI 34%-49%),while for patients with SR-cGVHD,the ORR,CR rate and PR rate were 81%(95%CI 70%-89%),26%(95%CI 11%-49%)and 51%(95%CI 34%-67%).In terms of safety,the adverse events of myelosuppression,cytomegalovirus reactivation and other infections increased after the use of ruxolitinib.The incidence of hemocytopenia was 17%(95%CI 10%-28%),and the reactivation rate of cytomegalovirus was 21%(95%CI 15%-29%),while the incidence of other infections was 18%(95%CI 9%-33%).Conclusion:Ruxolitinib can obtain high effective rate in the salvage treatment of adult patients with aGVHD and cGVHD.Attention should be paid to the occurrence of bone marrow suppression and infection.