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 (MG-ADL) 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 MG-ADL 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 At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone.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 One child was withdrawn from tacrolimus due to recurrent vomiting.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 CYP3A5 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. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.
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。