他克莫司治疗儿童重症肌无力的疗效研究  

Clinical effect of tacrolimus in the treatment of myasthenia gravis in children

作　　者：李久伟[1] 方方[1] 任晓暾[1] 张炜华[1] 杨欣英[1] 任长红[1] 巩帅[1] 吕俊兰[1] 王晓慧[1] 王旭[1] 吴沪生[1] 丁昌红[1] LI Jiu-Wei;FANG Fang;REN Xiao-Tun;ZHANG Wei-Hua;YANG Xin-Ying;REN Chang-Hong;GONG Shuai;LYU Jun-Lan;WANG Xiao-Hui;WANG Xu;WU Hu-Sheng;DING Chang-Hong(Department of Neurology,Beijing Children's Hospital Capital Medical University,National Center for Children's Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心/首都医科大学附属北京儿童医院神经内科,北京100045

出　　处：《中国当代儿科杂志》2020年第9期964-969,共6页Chinese Journal of Contemporary Pediatrics

摘　　要：目的评价他克莫司治疗儿童重症肌无力(MG)的疗效及安全性。方法采用他克莫司治疗28例MG儿童,运用重症肌无力日常生活(MG-ADL)量表于治疗1、3、6、9、12个月时评估他克莫司的疗效及安全性。结果他克莫司治疗1、3、6、9、12个月时的MG-ADL绝对评分与基线水平相比均降低(P<0.05),且呈逐渐降低趋势。他克莫司治疗1、3、6、9、12个月时的有效率分别为59%、81%、84%、88%、88%。他克莫司治疗6、9、12、18个月时累计停用泼尼松4、13、14、15例。所有患儿治疗期间均未出现病情反复。主要不良反应/事件有无症状血镁降低(5例);尿潜血阳性(1例),后自行转为阴性;均未因不良反应/事件停药。1例患儿因反复呕吐自行停药。根据CYP3A5基因型分为慢代谢组(慢代谢型,n=19)、非慢代谢组(快代谢型+中间型,n=9),慢代谢组患儿他克莫司剂量低于非慢代谢组(P<0.05),非慢代谢组他克莫司血药谷浓度低于慢代谢组(P<0.05),慢代谢组有效率高于非慢代谢组(P<0.05)。结论他克莫司治疗儿童MG疗效显著、安全性好,是需要免疫抑制剂治疗的MG患儿的良好选择。CYP3A5基因型对他克莫司使用剂量有一定的指导意义。Objective To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis(MG).Methods A total of 28 children with MG were treated with tacrolimus.MG-Activities of Daily Living(MGADL)scale was used to assess clinical outcome and safety after 1,3,6,9,and 12 months of treatment.Results After tacrolimus treatment,the MG-ADL score at 1,3,6,9 and 12 months was lower than that at baseline(P<0.05),and the MGADL score showed a gradually decreasing trend.The response rates to tacrolimus treatment at 1,3,6,9,and 12 months were 59%,81%,84%,88%,and 88%respectively.At 6,9,12,and 18 months of treatment,4,13,14,and 15 children respectively were withdrawn from prednisone.No recurrence was observed during treatment.Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child,which turned negative without special treatment,and tacrolimus was not stopped due to such adverse reactions/events.One child was withdrawn from tacrolimus due to recurrent vomiting.According to CYP3 A5 genotypes,all of the patients were divided into two groups:slow metabolic type(n=19)and non-slow metabolic type(fast metabolic type+intermediate type;n=9).The non-slow metabolism group received a higher dose of tacrolimus,but had a lower trough concentration of tacrolimus than the slow metabolism group(P<0.05).The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group(P<0.05).Conclusions Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy.CYP3 A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.

关 键 词：重症肌无力 免疫抑制剂 他克莫司 CYP3A5 儿童 

分 类 号：R746.1[医药卫生—神经病学与精神病学]