Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial
Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial
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DOI：
10.1016/s2352-4642(18)30099-3
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发表时间：
2018-07-01
影响因子：
36.4
通讯作者：
French, Jacqueline A.
中科院分区：
文献类型：
--
作者：
Curatolo, Paolo;Franz, David N.;French, Jacqueline A.
癫痫发生在结节性硬化症患者的70 - 90%。我们的目的是评估的疗效和安全性，连续依维莫司治疗难治性癫痫发作与结节性硬化症复杂的儿科患者参加了EXIST-3试验，双盲，安慰剂对照，随机，3期study.Methods这事后分析集中在儿科患者（年龄= 48周），并在99个中心在全球25个国家。简单地说，患有结节性硬化症综合征相关的难治性癫痫发作的患者，正在接受1 - 3种稳定剂量的抗癫痫药物，被随机分配（1：1：1）接受安慰剂，低暴露的依维莫司（3 - 7 ng/mL）或高暴露的依维莫司（9 - 15 ng/mL）。在核心阶段之后，患者可以进入扩展阶段，在最后一名患者完成核心阶段后48周内接受3 - 15 ng/mL的目标暴露范围的依维莫司。疗效终点为反应率（每周平均癫痫发作频率较基线降低>= 50%）和核心期12周维持期内以及整个扩展期间隔12周时癫痫发作频率降低的中位百分比。该研究注册于www.example.com，编号NCT 01713946。结果在2013年7月3日至2015年5月29日期间，299名儿科患者入组了该试验。在年轻亚组（= 6岁至
Background Epilepsy occurs in 70-90% of patients with tuberous sclerosis complex. We aimed to assess the efficacy and safety of adjunctive everolimus for treatment-refractory seizures associated with tuberous sclerosis complex in paediatric patients enrolled in the EXIST-3 trial, a double-blind, placebo-controlled, randomised, phase 3 study.Methods This post-hoc analysis focused on paediatric patients (age = 48 weeks) and was done at 99 centres in 25 countries worldwide. Briefly, patients with tuberous sclerosis complex-associated treatment-refractory seizures, who were receiving a stable dose of one to three antiepileptic drugs, were randomly assigned (1: 1: 1) to receive placebo, low-exposure everolimus (3-7 ng/mL), or high-exposure everolimus (9-15 ng/mL). Following the core phase, patients could enter the extension phase to receive everolimus at a targeted exposure range of 3-15 ng/mL up to 48 weeks after the last patient had completed the core phase. Efficacy endpoints were response rate (>= 50% of reduction from baseline in average weekly seizure frequency) and median percentage reduction in seizure frequency during the 12-week maintenance period of the core phase, and at 12-week intervals throughout the extension phase. This study is registered with ClinicalTrials.gov,number NCT01713946.Findings Between July 3, 2013, and May 29, 2015, 299 paediatric patients enrolled in the trial. In the younger subgroup (= 6 years to