摘要
目的 系统评价艾曲泊帕联合免疫抑制治疗(IST)对重型再生障碍性贫血(SAA)的疗效和安全性,为临床治疗SAA提供循证依据。方法 系统检索PubMed、Embase、Cochrane Library、ClinicalTrials.gov、维普网、中国知网、万方数据库,检索时限为建库至2023年5月。收集艾曲泊帕联合IST(试验组)对比单纯IST(对照组)的随机对照试验(RCT)和队列研究,对纳入研究进行资料提取、质量评价(Cochrane手册5.1.0)后,采用RevMan 5.4软件进行Meta分析、亚组分析、敏感性分析和发表偏倚分析。结果 共纳入12项研究,共计1 344例患者。与对照组相比,试验组患者3个月时的客观缓解率(ORR)(RR=1.34,95%CI为1.06~1.69,P=0.01)及完全缓解率(CRR)(RR=1.88,95%CI为1.31~2.71,P=0.000 6)、6个月时的ORR(RR=1.33,95%CI为1.23~1.43,P<0.000 01)及CRR(RR=1.88,95%CI为1.57~2.25,P<0.000 01)均显著升高;而2组患者12个月时的ORR(RR=0.99,95%CI为0.82~1.18,P=0.88)、12个月时的CRR(RR=1.02,95%CI为0.78~1.34,P=0.87)、2年总生存率(HR=0.61,95%CI为0.31~1.22,P=0.17)、2年无事件生存率(HR=0.81,95%CI为0.61~1.07,P=0.14)、克隆进化率(RR=1.01,95%CI为0.51~2.00,P=0.98)和肝/肾功能不全、皮疹等不良反应的发生率比较,差异均无统计学意义(P>0.05)。亚组分析结果显示,RCT和队列研究亚组中,试验组患者6个月时的ORR、6个月时的CRR均显著高于对照组(P<0.05),而试验组患者的2年总生存率、2年无事件生存率、克隆进化率与对照组比较,差异均无统计学意义(P>0.05)。敏感性分析和发表偏倚分析结果显示,本研究所得结果基本稳定且存在发表偏倚的可能性较小。结论 在SAA的IST方案中添加艾曲泊帕可以提高患者早期血液学缓解率,对短期生存无明显影响,且不会增加不良反应和克隆进化的发生。
OBJECTIVE To systematically evaluate the efficacy and safety of eltrombopag combined with immunosuppressive therapy(IST)for severe aplastic anemia(SAA),and to provide evidence-based basis for clinical treatment of SAA.METHODS Retrieved from PubMed,Embase,Cochrane Library,ClinicalTrials.gov,VIP,CNKI and Wanfang data,randomized controlled trials(RCTs)and cohort studies about eltrombopag combined with IST(trial group)versus IST alone(control group)were collected from the inception to May 2023.After data extraction and quality evaluation(Cochrane manual 5.1.0)of included studies,meta-analysis,subgroup analysis,sensitivity analysis and publication bias analysis were performed by using RevMan 5.4 software.RESULTS A total of 12 studies were screened,including 1344 patients.Compared with control group,objective remission rate(ORR)(RR=1.34,95%CI was 1.06-1.69,P=0.01)and complete response rate(CRR)(RR=1.88,95%CI was 1.31-2.71,P=0.0006)at 3 months,ORR(RR=1.33,95%CI was 1.23-1.43,P<0.00001)and CRR(RR=1.88,95%CI was 1.57-2.25,P<0.00001)at 6 months were significantly increased in trial group.There was no statistically significant difference between the two groups in ORR(RR=0.99,95%CI was 0.82-1.18,P=0.88)and CRR(RR=1.02,95%CI was 0.78-1.34,P=0.87)at 12 months,two-year overall survival(OS)rate(HR=0.61,95%CI was 0.31-1.22,P=0.17),two-year event-free survival(EFS)rate(HR=0.81,95%CI was 0.61-1.07,P=0.14),clone evolution rate(RR=1.01,95%CI was 0.51-2.00,P=0.98)or the incidence of adverse drug reactions such as liver/renal insufficiency,rash(P>0.05).Results of subgroup analysis showed that ORR and CRR of trial group at 6 months were higher than those of the control group in RCT and the cohort study subgroups(P<0.05).There was no statistically significant difference in the two-year OS rate,two-year EFS rate or clone evolution rate between trial group and control group in the two subgroups(P>0.05).The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small.CONCLUSIONS The addition of eltrombopag in the IST regimen of SAA can improve the early hematological remission rate of patients,has no significant impact on short-term survival,and will not increase the occurrence of adverse drug reactions and clonal evolution.
作者
李碧云
韩亚辉
殷楚云
杜伟闯
李远方
王叨
LI Biyun;HAN Yahui;YIN Chuyun;DU Weichuang;LI Yuanfang;WANG Dao(Dept.of Children’s Hematology and Oncology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Dept.of Pediatric Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中国药房》
CAS
北大核心
2023年第15期1891-1898,共8页
China Pharmacy
基金
河南省高等学校重点科研项目资助计划(No.22A320050)。
关键词
再生障碍性贫血
艾曲泊帕
免疫抑制治疗
不良反应
severe aplastic anemia
eltrombopag
immunosuppressive therapy
adverse reaction
