Sperling Michael R, Harvey Jay, Grinnell Todd, Cheng Hailong, Blum David
Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
Epilepsia. 2015 Apr;56(4):546-55. doi: 10.1111/epi.12934. Epub 2015 Feb 16.
To assess the efficacy and safety of eslicarbazepine acetate (ESL) as monotherapy in North American patients with partial-onset seizures (POS).
This multicenter, randomized, double-blind "withdrawal to monotherapy" study used historical control data as the comparator. Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy. Following an 8-week baseline period, patients were randomized 2:1 to receive ESL 1,600 mg (n = 128) or 1,200 mg QD (n = 65) for 18 weeks. The primary end point was the proportion of patients meeting predefined exit criteria (signifying worsening seizure control). Treatment was considered effective if the 95% upper confidence limit (UCL) for the Kaplan-Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control (65.3%).
Kaplan-Meier estimated exit rates were: ESL 1,600 mg, 28.7% (95% CI 21.2-38.1%) and 1,200 mg, 44.4% (32.5-58.3%). The difference between doses was not significant (p = 0.07). For both doses, the 95% UCLs for the exit rate were ˂ 65.3%; ESL monotherapy was considered superior to the historical control. There was no statistically significant increase in the risk of study exit related to carbamazepine use. Nine (7.6%) and five patients (8.3%) remained seizure-free during the 10-week monotherapy period, while taking ESL 1,600 and 1,200 mg, respectively. The reductions in median standardized seizure frequency (seizures per 28 days) between baseline and the 18-week treatment period were: ESL 1,600 mg, 42% and 1,200 mg, 31%. Treatment-emergent adverse events (TEAEs) occurring in ≥ 10% of patients were dizziness, headache, fatigue, somnolence, nausea, and nasopharyngitis. The TEAE most frequently leading to discontinuation was hyponatremia (2.1%).
ESL was efficacious and well tolerated as monotherapy in North American patients, and led to a reduction in seizure frequency. Exit rates for ESL 1,600 and 1,200 mg QD were superior to the historical control; the difference in exit rates between doses was not statistically significant.
评估醋酸艾司利卡西平（ESL）作为北美部分性发作（POS）患者单药治疗的疗效和安全性。
这项多中心、随机、双盲“撤药至单药治疗”研究采用历史对照数据作为比较对象。使用一至两种抗癫痫药物治疗后病情仍未得到有效控制的POS成年患者逐渐转换为ESL单药治疗。在为期8周的基线期之后，患者按2:1随机分组，分别接受1600 mg ESL（n = 128）或每日1200 mg ESL（n = 65）治疗18周。主要终点是达到预定义退出标准（表明癫痫控制恶化）的患者比例。如果Kaplan-Meier估计退出率的95%置信上限（UCL）低于根据历史对照计算得出的退出率阈值（65.3%），则认为治疗有效。
Kaplan-Meier估计退出率分别为：1600 mg ESL组为28.7%（95%CI 21.2 - 38.1%），1200 mg ESL组为44.4%（32.5 - 58.3%）。剂量之间的差异无统计学意义（p = 0.07）。对于两种剂量，退出率的95%UCL均˂ 65.3%；ESL单药治疗被认为优于历史对照。与使用卡马西平相关的研究退出风险没有统计学上的显著增加。在10周的单药治疗期内，分别有9名（7.6%）和5名患者（8.3%）在服用1600 mg和1200 mg ESL时无癫痫发作。基线期至18周治疗期之间，标准化癫痫发作频率中位数（每28天发作次数）的降低幅度分别为：1600 mg ESL组为42%，1200 mg ESL组为31%。≥10%的患者出现的治疗中出现的不良事件（TEAE）有头晕、头痛、疲劳、嗜睡、恶心和鼻咽炎。最常导致停药的TEAE是低钠血症（2.1%）。
ESL作为北美患者的单药治疗有效且耐受性良好，并导致癫痫发作频率降低。每日1600 mg和1200 mg ESL的退出率优于历史对照；剂量之间的退出率差异无统计学意义。
