第三代非甾体类芳香化酶抑制剂治疗矮身材儿童有效性与安全性的系统评价  

Efficacy and safety of the third-generation non-steroidal aromatase inhibitors for children with short stature:a systematic review

作　　者：刘峥 杨春松[1,2,3,4] 曾力楠[1,2,3,4] 贾知军[1,2,3,4,6] 成果 余勤[4,9] 吴瑾 张伶俐 LIU Zheng;YANG Chunsong;ZENG Linan;JIA Zhijun;CHENG Guo;YU Qin;WU Jin;ZHANG Lingli(Department of Pharmacy,West China Second University Hospital,Sichuan University,Chengdu 610041,P.R.China;Evidence-Based Pharmacy Center,West China Second University Hospital,Sichuan University,Chengdu 610041,P.R.China;NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation,Chengdu 610041,P.R.China;Key Laboratory of Birth Defects and Related Diseases of Women and Children,Sichuan University,Ministry of Education,Chengdu 610041,P.R.China;West China School of Medicine,Sichuan University,Chengdu 610041,P.R.China;West China School of Pharmacy,Sichuan University,Chengdu 610041,P.R.China;Department of Pediatrics,West China Second University Hospital,Sichuan University,Chengdu 610041,P.R.China;Laboratory of Molecular Translational Medicine,Center for Translational Medicine,Sichuan University,Chengdu 610041,P.R.China;National Drug Clinical Trial Institute,West China Second University Hospital,Sichuan University,Chengdu 610041,P.R.China;Chinese Evidence-based Medicine Center,West China Hospital,Sichuan University,Chengdu 610041,P.R.China)

机构地区：[1]四川大学华西第二医院药学部,成都610041 [2]四川大学华西第二医院循证药学中心,成都610041 [3]国家药品监督管理局药物制剂体内外相关性技术研究重点实验室,成都610041 [4]出生缺陷与相关妇儿疾病教育部重点实验室,成都610041 [5]四川大学华西临床医学院,成都610041 [6]四川大学华西药学院,成都610041 [7]四川大学华西第二医院儿科,成都610041 [8]四川大学转化医学中心分子转化医学实验室,成都610041 [9]四川大学华西第二医院国家药物临床试验机构,成都610041 [10]四川大学华西医院中国循证医学中心,成都610041

出　　处：《中国循证医学杂志》2024年第4期429-438,共10页Chinese Journal of Evidence-based Medicine

基　　金：四川大学华西医学中心医学交叉项目(国家妇幼医疗资源配置优化关键技术研究)。

摘　　要：目的青春中晚期矮身材儿童的生长潜能可能受限于雌激素对骨骺闭合的影响,近年来有临床研究将第三代非甾体类芳香化酶抑制剂(AIs)用于治疗矮身材儿童,但属超说明书用药。本研究旨在系统评价第三代非甾体类AIs治疗矮身材儿童的有效性与安全性,为临床合理用药提供循证证据。方法计算机检索PubMed、Embase、Cochrane Library、CNKI、WanFang Data、VIP和CBM数据库,搜集重组人生长激素(rhGH)联合或不联合第三代非甾体类AIs治疗矮身材儿童的相关临床研究,检索时限均从建库至2022年12月28日。由两名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险,采用RevMan 5.3软件进行Meta分析。结果最终纳入文献18篇,共9项随机对照试验和9项队列研究,包括患者1053例。Meta分析结果显示:在有效性方面,试验组患者的最终成年身高[MD=2.48,95%CI(2.02,2.94),P<0.01]、治疗结束时的预测成年身高[MD=4.27,95%CI(2.71,5.83),P<0.01]、预测成年身高差值[MD=4.26,95%CI(3.23,5.28),P<0.01]、骨龄[MD=-0.62,95%CI(-0.89,-0.36),P<0.01]、骨龄差值/实际年龄差值[MD=-0.47,95%CI(-0.56,-0.37),P<0.01]、生长速率[MD=1.34,95%CI(0.89,1.78),P<0.01]均优于对照组,但两组治疗结束时的身高[MD=4.03,95%CI(-0.01,8.06),P=0.05]差异无统计学意义;在安全性方面,试验组的不良事件总发生率[RR=2.10,95%CI(1.48,2.99),P<0.01]高于对照组,其中两组的内分泌系统不良事件、皮肤及皮下组织系统不良事件发生率差异有统计学意义(P<0.05),两组的肝胆系统、肾脏泌尿系统、代谢及营养类、胃肠道系统、肌肉骨骼系统、血液与淋巴系统、血管与淋巴管系统及神经精神系统不良事件的发生率差异则无统计学意义(P>0.05)。结论现有证据表明,第三代非甾体类AIs联合rhGH可有效改善矮身材儿童的最终成年身高,但可能增加不良事件的发生率。受纳入研究质量及随访时间的限制,未来�Objective The growth potential of children with short stature in middle and late adolescence may be limited by the effect of estrogen on epiphyseal closure.In recent years,the third generation of non-steroidal aromatase inhibitors(AIs)have been used in the treatment of short stature but with off-label.This study aimed to systematically review the efficacy and safety of the third-generation non-steroidal AIs in the treatment of children with short stature,and to provide evidences for rational drug use in clinical practice.Methods We searched PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP and CBM from inception to December 28,2022.Relevant studies on the treatment for children with short stature using the recombinant human growth hormone(rhGH)combined with or without the thirdgeneration non-steroidal AIs were collected.Two reviewers independently screened the literature,extracted data,and evaluated the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.3 software.Results A total of 18 articles were finally included,involving 9 randomized controlled trials and 9 cohort studies,with a total of 1053 patients.The Meta-analysis showed that:(1)in terms of efficacy,the final adult height(MD=2.48,95%CI 2.02 to 2.94,P<0.01),predicted adult height(MD=4.27,95%CI 2.71 to 5.83,P<0.01),predicted adult height difference(MD=4.26,95%CI 3.23 to 5.28,P<0.01),bone age(MD=−0.62,95%CI−0.89 to−0.36,P<0.01),bone age difference/actual age difference(MD=−0.47,95%CI−0.56 to−0.37,P<0.01),and growth velocity(MD=1.34,95%CI 0.89 to 1.78,P<0.01)at the end of treatment in the experimental group were better than those in the control group,but there was no statistical difference in the height at the end of treatment between the two groups(MD=4.03,95%CI−0.01 to 8.06,P=0.05).(2)in terms of safety,the total incidence of adverse events in the experimental group(RR=2.10,95%CI 1.48 to 2.99,P<0.01)was higher than that in the control group,among which the incidence of adverse events in the endocrine system an

关 键 词：芳香化酶抑制剂 来曲唑 阿那曲唑 重组人生长激素 矮身材 系统评价 

分 类 号：R725.8[医药卫生—儿科] R969.3[医药卫生—临床医学]