中国循证儿科杂志 ›› 2021, Vol. 16 ›› Issue (4): 269-274.

• 论著 • 上一篇    下一篇

基于随访6个月疗效结局的加用吡仑帕奈治疗儿童药物难治性癫的单中心前瞻性队列研究

张捷, 谢涵邓泂许晗刘先禹林泽鸿常旭婷吴晔   

  1. 北京大学第一医院 北京,100034
  • 收稿日期:2021-08-25 修回日期:2021-08-25 出版日期:2021-08-25 发布日期:2021-08-25
  • 通讯作者: 吴晔

Perampanel in the treatment of children with drug-resistant epilepsy based on the follow-up of 6-month efficacy:A single-center prospective cohort study

ZHANG Jie, XIE Han, DENG Jiong, XU Han, LIU Xianyu, LIN Zehong, CHANG Xuting, WU Ye   

  1. Peking University First Hospital, Beijing 100034, China
  • Received:2021-08-25 Revised:2021-08-25 Online:2021-08-25 Published:2021-08-25
  • Contact: WU Ye

摘要: 目的:探讨吡仑帕奈治疗儿童药物难治性癫的疗效与安全性。 设计:前瞻性队列研究。 方法:以2020年1~12月于北京大学第一医院就诊、年龄0~18岁、确诊为药物难治性癫、加用吡仑帕奈治疗的患儿为队列人群,以治疗至少6个月为队列终点,并以疗效为因变量,以性别、病因、综合征、基线发作频率、起病年龄、加药时年龄、加药时病程、用药剂量及抗癫治疗种数为自变量,行单因素分析及多因素Logistic回归分析疗效相关因素,并观察吡仑帕奈治疗儿童药物难治性癫的不良反应。 主要结局指标:末次随访时(近1月内)较基线期发作频率减少≥50%。 结果:(1)基线信息:①共纳入50例,男34例,女16例,均随访至少6个月。②13例明确诊断癫综合征,包括婴儿痉挛症6例、Lennox-Gastaut综合征2例、睡眠中癫性电持续状态相关脑病3例、Rasmussen脑炎2例。③33例(66.0%)存在明确的癫病因,包括结构性19例、遗传性9例、免疫性4例、代谢性1例。④基线发作频率为2周发作1次至每天数百次,其中9例(18.0%)发作<1次/d,18例(36.0%)发作~10次/d,16例(32.0%)发作~100次/d,7例(14.0%)发作>100次/d。⑤基线期合并抗癫治疗种数3(1~6)种,既往治疗种数3(0~10)种。(2)吡仑帕奈用药信息:加用时年龄64.5月(4月至18岁);加用时病程22.0月(2月至17.3年);末次随访时为加用吡仑帕奈后8.0(6.0~14.0)月。末次随访时每日最大剂量为0.175(0.06~0.5)mg·kg-1·d-1或4(0.5~12)mg·d-1。(3)疗效及相关因素分析:有效率46.0%(23/50),末次随访时41例(82.0%)保留吡仑帕奈,9例停药均因疗效不佳。未发现吡仑帕奈疗效与性别、病因、综合征、基线发作频率、起病年龄、加药时年龄、加药时病程、用药剂量、治疗种数相关。(4)安全性:6例(12.0%)在用药期间有情绪烦躁、嗜睡表现,未观察到其他严重不良反应。 结论:吡仑帕奈治疗儿童药物难治性癫总体有效率为46.0%,安全性及耐受性相对较好,未发现影响疗效相关因素。

关键词: 吡仑帕奈, 癫痫, 儿童

Abstract: Background: There are few studies on the efficacy and safety of perampanel in children with drug-resistant epilepsy, and the efficacy and safety are not clear. Objective: To investigate the efficacy and safety of perampanel in the treatment of children with drug-resistant epilepsy. Design: Cohort study. Methods: Children aged 0-18 years who were diagnosed with drug-resistant epilepsy and treated with perampanel in Peking University First Hospital from January to December 2020 were included in the cohort study, and the end point was at least 6 months' treatment. Efficacy was the dependent variable, and the gender, etiology, epileptic syndrome, baseline frequency of seizures, age at onset, age at time of dosing, course of disease at dosing, dosage of drugs, number of treatments were independent variables. The univariate and multivariate logistic regression analysis were used to analyze the related factors of efficacy. The adverse reactions of perampanel in the treatment of children with drug-resistant epilepsy were also analyzed. Main outcome measures: The frequency of seizures decreased ≥50% from baseline at the last follow-up (within 1 month) . Results: A total of 50 patients were included (34 males and 16 females),and all the patients were followed up at least 6 months. The epileptic syndromes included infantile spasms in 6 cases, Lennox-Gastaut syndrome in 2 cases, epileptic encephalopathy with electrical status epilepticus during sleep in 3 cases, and Rasmussen encephalitis in 2 cases. Specific causes of epilepsy were found in 66.0% (33/50) of the patients, including structural causes in 19 cases, genetic causes in 9 cases, immunological causes in 4 cases, and metabolic causes in 1 case. The baseline frequency of seizures ranged form once per 2 weeks to hundreds of times per day. Eighteen percent (9/50) of the patients had seizure less than once a day, 36.0% (18/50) of the patients with seizures of 1-10 times per day, 32.0% (16/50) with seizures of 1-10 times per day, 14.0% (7/50) with seizures of more than 100 times per day. Three types of treatments (range from 1 to 6 types) were used in combination with perampanel, and three types of treatments (range from 0-10 types) were previously used. The age at time of dosing was 64.5 months (4 months to 18 years), and course of disease at dosing was 22.0 months (2 months to 17.3 years). The duration of perampanel at the last follow-up was 8.0 (6.0-14.0) months. At the last follow-up, the maximum daily dose of perampanel was 0.175 (0.06-0.5) mg·kg-1·d-1 and 4 (0.5-2) mg·d-1.The rate of efficacy was 46.0%(23/50). At the last follow-up, 41 patients were treated with perampanel, and the retention rate was 82.0%. Nine patients stopped treatments because of poor efficacy. No correlation was found between the efficacy and gender, etiology, epileptic syndrome, baseline frequency of seizures, age at onset, age at time of dosing, course of disease at dosing, dosage of drugs, or number of treatments. Six patients (12.0%) were observed with irritability and drowsiness during the treatment, and no other serious adverse reactions were observed. Conclusion: The overall rate of efficacy of using perampanel to treat drug-resistant epilepsy was 46%. The safety and tolerability of perampanel in the treatment of children with drug-resistant epilepsy were relatively good, and no related factors with efficacy were found.

Key words: Perampanel, Epilepsy, Children