拉考沙胺添加治疗在中国儿童局灶性癫痫发作中的安全性与有效性——一项全球多中心单臂研究期中分析  

Safety and efficacy of oral Lacosamide as an add-on therapy in Chinese children with partial-onset seizures:an interim analysis of a global multicenter single-arm study

作　　者：姜玉武[1] 王艺 钟建民[3] 廖建湘[4] 江佩芳[5] 蒋莉[6] 梁建民[7] 高玲玲 孙薇薇 李霄茜 陈思杰 Jiang Yuwu;Wang Yi;Zhong Jianmin;Liao Jianxiang;Jiang Peifang;Jiang Li;Liang Jianmin;Gao Lingling;Sun Weiwei;Li Xiaoqian;Chen Sijie(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Neurology,Children′s Hospital of Fudan University,Shanghai 201102,China;Department of Neurology,Jiangxi Provincial Children′s Hospital,Nanchang 330006,China;Department of Neurology,Shenzhen Children′s Hospital,Shenzhen 518038,China;Department of Neurology,Children′s Hospital of Zhejiang University School of Medicine,Hangzhou 310052,China;Department of Neurology,Children′s Hospital of Chongqing Medical University,Chongqing 400014,China;Department of Pediatric Neurology,the First Hospital of Jilin University,Changchun 130021,China;UCB Pharma,Shanghai 200001,China)

机构地区：[1]北京大学第一医院儿科,北京100034 [2]复旦大学附属儿科医院神经内科,上海201102 [3]江西省儿童医院神经内科,南昌330006 [4]深圳市儿童医院神经内科,深圳518038 [5]浙江大学医学院附属儿童医院神经内科,杭州310052 [6]重庆医科大学附属儿童医院神经内科,重庆400014 [7]吉林大学第一医院小儿神经内科,长春130021 [8]优时比制药,上海200001

出　　处：《中华实用儿科临床杂志》2023年第11期850-856,共7页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的评估拉考沙胺添加治疗用于中国局灶性癫痫发作儿童的安全性、耐受性和有效性。方法SP848是一项全球多中心单臂研究,收集2018年4月至2019年5月在全国7所医院接受拉考沙胺添加治疗的4~17岁中国局灶性癫痫发作患儿60例,在足疗程且至少使用2种抗癫痫发作药(同期或序贯)治疗后,观察到患儿局灶性癫痫仍然控制不佳;添加口服拉考沙胺口服溶液(糖浆)或片剂。最低起始口服剂量为2 mg/(kg·d),研究期间最大允许服用剂量为12 mg/(kg·d)或600 mg/d,研究者根据患儿的耐受性和癫痫发作控制水平调整服用剂量。记录自基线期至末次访视每28 d局灶性癫痫的发作频率及中位变化百分比,包括50%应答率及75%应答率。结果60例中国患儿进入期中分析,患儿平均年龄9.18(4.00~15.40)岁,男39例,女21例,平均癫痫病程为5.04(0.50~15.20)年。其中43例(71.7%)仍在接受治疗,1例(1.7%)完成了6个月至1年的随访,14例(23.3%)完成了6个月随访。自基线期至末次访视,患儿每28 d局灶性癫痫发作频率中位变化为-2.91,百分比变化中位数为-25.46%,50%和75%应答率分别为40.0%、28.3%。共有52例(86.7%)发生265起治疗中出现的不良事件(TEAE),其中11例(18.3%)发生19起严重TEAE,37例(61.7%)发生127起药物相关TEAE,11例(18.3%)发生16起导致终止研究的TEAE。最常见的TEAE为上呼吸道感染(20例,33.3%)、嗜睡(16例,26.7%)、头晕(15例,25.0%)和呕吐(13例,21.7%)。治疗期间未发现具有临床意义的心电图异常变化。结论对其他药物控制不佳的≥4岁中国局灶性癫痫患儿,拉考沙胺是一种有效的添加治疗药物,耐受性良好。安全性特征与儿童和成人已报道的研究一致,未发现新的安全性问题。Objective To evaluate the long-term safety,tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially,partial seizures were still poorly controlled and Lacosamide oral solution(syrup)or tablets were added.The minimum initial oral dose was 2 mg/(kg·d),and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded,including 50%responder rate and 75%responder rate.Results A total of 60 Chinese children with the mean age of 9.18(4.00-15.40)years were included in this interim analysis,involving 39 males and 21 females.The mean course of epilepsy was 5.04(0.50-15.20)years.A total of 43 patients(71.7%)still have been treated.One patient(1.7%)has completed the 6-12 months of follow-up,and 14 patients(23.3%)have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was-2.91,with its median percentage as-25.46%,and the proportions of≥50%,while≥75%responder rate were 40.0%and 28.3%,respectively.A total of 52 patients(86.7%)had 265 treatment emergent adverse events(TEAE),11 patients(18.3%)had 19 serious TEAE,37 patients(61.7%)had 127 drug-related TEAE,and 11 patients(18.3%)had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections(20 cases,33.3%),followed by drowsiness(16 cases,26.7%),dizziness(15 cases,25.0%)and vomiting(13 c

关 键 词：抗癫痫发作药 拉考沙胺 癫痫 局灶性发作 安全性 有效性 

分 类 号：R742.1[医药卫生—神经病学与精神病学]