芦可替尼治疗中国人群难治性移植物抗宿主病效果和安全性的Meta分析

Efficacy and safety of ruxolitinib for refractory graft-versus-host disease in Chinese population:a Meta-analysis

目的系统评价芦可替尼治疗中国人群难治性移植物抗宿主病(SR-GVHD)的效果及安全性。方法以"芦可替尼""移植物抗宿主病""ruxolitinib""Graft vs Host Disease""graft versus host disease""Graft-Versus-Host Disease"为关键词,检索中国知网、万方、维普、中国生物医学文献数据库、PubMed、Ebscore Medline、EMBASE、Web of Science核心合集以及Cochrane Library,检索时限为自建库起至2021年12月7日。根据纳入及排除标准筛选芦可替尼治疗中国人群SR-GVHD的相关文献,并提取文献特征;结局指标为总体客观缓解率(ORR)、激素减量及停用比例、生存指标、不良反应发生率等。采用Stata 16.0软件或R3.6.3软件对ORR、受累器官缓解率、12个月总生存率、总体死亡率和因移植物抗宿主病死亡率进行Meta分析;对患者激素使用情况和不良反应进行统计。结果纳入19篇关于芦可替尼治疗中国人群SR-GVHD的文献,共775例患者。Meta分析结果显示,芦可替尼治疗急性移植物抗宿主病(aGVHD)患者ORR为84%(285/339),各研究间具有中等异质性(I2=62.04%,P<0.01),其中完全缓解(CR)率、部分缓解(PR)率和未缓解(NR)率分别为56%(190/339)、28%(95/339)和14%(47/339);治疗慢性移植物抗宿主病(cGVHD)患者的ORR为77%(332/431),各研究间具有中等异质性(I2=50.17%,P=0.02),其中CR率、PR率和NR率分别为36%(155/431)、41%(177/431)和21%(91/431)。aGVHD患者中有46.5%激素减量,34.9%激素停用;cGVHD患者中有28.2%激素减量,36.9%激素停用。SR-GVHD患者经芦可替尼治疗后的12个月总生存率为71%(95%CI:63%~79%,I2=72.70%,P<0.01)。共发生各类不良反应760例次,其中病毒感染[287例次(36.0%)]和血细胞减少[269例次(34.7%)]是最常见的不良反应。结论芦可替尼可有效治疗中国人群SR-GVHD,有助于减少激素依赖,延长患者生存期。

Objective To systematically evaluate the efficacy and safety of ruxolitinib in the treatment of Chinese patients with refractory graft-versus-host disease(SR-GVHD)by using meta-analysis.Methods China National Knowledge Infrastructure(CNKI),WanFang database,VIP database,China Biology Medicine disc,PubMed,Ebscore Medline,EMBASE,Web of Science Core Collection and Cochrane Library were searched by using"ruxolitinib""Graft vs Host Disease""graft versus host disease""Graft-Versus-Host Disease"as key words.The retrieve time was from the establishment of the database to December 7th,2021.The related literatures of ruxolitinib for Chinese patients with SR-GVHD were screened according to inclusion and exclusion criteria,and the characteristics of the literatures were extracted.Outcomes indexes included overall objective response rate(ORR),proportion of hormone reduction and discontinuation,survival indexes and incidence of adverse events.Meta-analysis of ORR,remission rate of affected organs,12-month overall survival rate,overall mortality and mortality due to graft-versus-host disease(GVHD)were performed by using Stata 16.0 software or R3.6.3 software.The statistics analysis was performed on the hormone usage and adverse events.Results A total of 19 literatures involving 775 Chinese patients with SR-GVHD treated by ruxolitinib were included.Meta analysis showed that the ORR of ruxolitinib for treatment of acute GVHD(aGVHD)was 84%(285/339),with moderate heterogeneity among studies(I2=62.04%,P<0.01),and the complete remission(CR)rate,partial remission(PR)rate and non-remission(NR)rate was 56%(190/339),28%(95/339),and 14%(47/339),respectively.The ORR of ruxolitinib for treatment of chronic GVHD(cGVHD)was 77%(332/431),with moderate heterogeneity among studies(I2=50.17%,P=0.02),and the CR rate,PR rate and NR rate was 36%(155/431),41%(177/431)and 21%(91/431),respectively.As for hormone usage,46.51%of aGVHD patients had steroid reduction and 34.88%patients had steroid discontinuation.Similarly,28.2%of patients with cGVHD had steroid reduction and 36.9%had steroid discontinuation.The overall 12-month survival rate of patients with SR-GVHD after the treatment of ruxolitinib was 71%(95%CI:63%-79%,I2=72.70%,P<0.01).Adverse events occurred for 760 times in total,among which 287 times(36.0%)of viral infection and 269 times(34.7%)of hemocytopenia were the most common adverse events.Conclusions Ruxolitinib is effective in the treatment of Chinese patients with SR-GVHD,and it helps reduce hormone-dependency and prolong the survival time.