应用机器学习分析吡仑帕奈单药治疗儿童局灶性癫痫临床疗效的影响因素

Analysis of influencing factors for clinical efficacy of Perampanel monotherapy in children with focal epilepsy based on machine learning

目的分析吡仑帕奈单药治疗儿童局灶性癫痫临床疗效的影响因素,促进临床合理用药。方法应用回顾性研究方法分析2021年6月至2022年8月在华中科技大学同济医学院附属武汉儿童医院确诊为癫痫局灶性发作的患儿资料。以吡仑帕奈单药治疗第3、6、12个月疗效为因变量,患儿性别、起病年龄、吡仑帕奈单药治疗的初始年龄、病程、体重、体重指数(BMI)、发作频率、癫痫综合征、病因、既往史、发育迟滞、起始剂量及维持剂量、血药浓度、CYP3A4、CYP3A5基因突变情况等因素为自变量,采用Cox比例风险回归分析各项因素对吡仑帕奈单药治疗疗效的影响;采用机器学习随机森林模型及决策树模型分析影响疗效因素的重要性序列并寻找最佳分类界值切点。结果本研究共纳入43例患儿(男31例,女12例),起病年龄为(7.6±2.1)岁,开始使用吡仑帕奈单药治疗年龄为(7.8±2.7)岁。Cox比例风险回归分析提示患儿BMI数值越大,吡仑帕奈治疗局灶性癫痫的疗效越差(HR=0.74,95%CI:0.55~0.99,P=0.045),且通过机器学习发现患儿的BMI是影响临床疗效的显著性协变量,当BMI≥21.8 kg/m^(2)时负向影响疗效更显著。结论吡仑帕奈单药治疗儿童局灶性癫痫的临床疗效与患儿的BMI值相关,单药治疗肥胖癫痫患儿可能需适当增加吡仑帕奈剂量以控制发作。

Objective To analyze influencing factors for the clinical efficacy of Perampanel monotherapy in children with focal epilepsy and promote rational clinical use of Perampanel.Methods Children who were diagnosed with focal epilepsy and treated with Perampanel monotherapy in Wuhan Children′s Hospital,Tongji Medical College,Huazhong University of Science&Technology from June 2021 to August 2022 were included in this retrospective study.Efficacy at 3,6 and 12 months after treatment was taken as the dependent variable.The gender,age at onset,age at initiation of Perampanel monotherapy,course of disease,weight,body mass index(BMI),seizure frequency,epilepsy syndrome,etiology,previous clinical history,developmental retardation,starting and maintenance doses,blood concentration,CYP3A4 and CYP3A5 gene mutations were taken as the independent variables.The effects of these factors on the efficacy of Perampanel monotherapy were analyzed using the Cox proportional hazards regression.The random forest and decision tree models were used to sequence the significance of the influencing factors and find the optimal cut-point for classification.Results A total of 43 children(31 boys and 12 girls)were enrolled in this study.The average age at onset was(7.6±2.1)years,and the average age at initiation of Perampanel monotherapy was(7.8±2.7)years.The Cox proportional hazards regression analysis indicated that the greater the BMI,the worse the efficacy of Perampanel(HR=0.74,95%CI:0.55-0.99,P=0.045).Through machine learning,the BMI was found to be a significant covariate affecting the efficacy,and when BMI≥21.8 kg/m^(2),the negative effect was more significant.Conclusions The clinical efficacy of Perampanel monotherapy in children with focal epilepsy is related to BMI.The dose of Perampanel for obese children with epilepsy may need to appropriately increase.