吡仑帕奈单药治疗局灶性癫痫患者的疗效及安全性研究

Efficacy and safety of perampanel monotherapy for focal epilepsy

目的探讨吡仑帕奈(PER)单药治疗局灶性癫痫患者的疗效及安全性。方法选取浙江大学医学院附属第二医院2020年1月至2022年12月期间使用PER单药治疗的≥4岁的局灶性癫痫患者,纳入完成1年随访及血药浓度检测的病例进行回顾性分析,计算患者随访1年的无发作率、有效率及不良反应发生率。并统计分析PER的疗效及安全性与药物血药浓度之间的相关性。结果本研究共纳入41例接受PER单药治疗的局灶性癫痫患者。药物维持剂量中位数为4 mg。改良意向性分析显示,PER单药治疗1年随访时患者的无发作率和有效率分别为58%和66%。伴有局灶扩展至双侧强直阵挛发作及睡眠相关发作癫痫病程较短的患者1年随访时无发作率更高,无发作的患者癫痫病程更短。有睡眠相关发作及癫痫病程较短的患者1年随访时的有效率更高。41例患者中10例(24%)出现不良反应,常见的不良反应有头晕、易怒及肝功能损害等,其中2例因不良反应停药。41例患者的PER平均血药浓度为318.27 ng/mL(范围53~689 ng/mL),平均剂量为3.83 mg(范围2~6 mg),血药浓度与剂量之间呈正相关(r=0.646,P<0.001)。治疗有效的患者的PER血药浓度低于无效者(P<0.05)。结论低剂量PER单药治疗局灶性癫痫患者在随访1年时具有较好的疗效及耐受性,其无发作率及有效率与癫痫患者的一些临床特征相关。

Objective To investigate efficacy and safety of perampanel(PER)monotherapy for focal epilepsy.Methods Patients aged≥4 years with focal epilepsy who received PER monotherapy,completed one-year follow-up and blood drug concentration detection were selected from the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2020 to December 2022.Retrospective analysis was performed on clinical data of these patients.The seizure-free rates,responder rates,and adverse events(AE)rates were calculated at one-year follow-up.Association of the efficacy and safety of PER with blood drug concentration was analyzed.Results A total of 41 patients with focal epilepsy who received PER monotherapy were included in this study.The median maintenance dose of the drug was 4 mg.Modified intent-to-treat analysis demonstrated that the seizure-free rate and responder rates of PER monotherapy at one-year follow-up were 58%and 66%,respectively.The patients with focal to bilateral tonic-clonic seizures and sleep-related seizures had a high seizure-free rate at one-year follow-up,while the patients with seizure-free had a shorter duration of epilepsy.The patients with sleep-related seizures and short duration of seizures had much high responder rate at one-year follow-up.Among 41 patients,10 patients(24%)had adverse reactions.Common adverse reactions included dizziness,irritability and abnormal liver function.Two patients stopped taking medication due to adverse reactions.The average blood PER concentration of 41 patients was 318.27 ng/mL(range 53~689 ng/mL),and the average dose was 3.83 mg(range 2~6 mg).There was a positive correlation between blood drug concentration and dose(r=0.646,P<0.001).Blood drug concentration of PER with effective treatment was lower than who with ineffective treatment(P<0.05).Conclusion Low dose PER monotherapy has good efficacy and tolerability in patients with focal epilepsy at one-year follow-up,and its seizure-free rate and responder rate are related to some clinical characteristics of patients with epilepsy.Blood drug concentration of PER of patients with effective treatment was lower than who with ineffective treatment(P<0.05).