Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University Salzburg, Salzburg, Austria.
Center for Cognitive Neuroscience, Salzburg, Austria.
Epilepsia. 2018 Feb;59(2):479-491. doi: 10.1111/epi.13993. Epub 2018 Jan 25.
We assessed the efficacy and safety of once-daily eslicarbazepine acetate in comparison with twice-daily (BID) controlled-release carbamazepine (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients.
This randomized, double-blind, noninferiority trial (NCT01162460) utilized a stepwise design with 3 dose levels. Patients who remained seizure-free for the 26-week evaluation period (level A: eslicarbazepine acetate 800 mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period. If a seizure occurred during the evaluation period, patients were titrated to the next target level (level B: eslicarbazepine acetate 1200 mg/carbamazepine-CR 400 mg BID, level C: eslicarbazepine acetate 1600 mg/carbamazepine-CR 600 mg BID) and the evaluation period began again. The primary endpoint was the proportion of seizure-free patients for 6 months after stabilization in the per protocol set. The predefined noninferiority criteria were -12% absolute and -20% relative difference between treatment groups.
Eight hundred fifteen patients were randomly assigned; 785 (388 in the eslicarbazepine acetate group and 397 in the carbamazepine-CR group) were included in the per protocol set, and 813 (401 in the eslicarbazepine acetate group and 412 in the carbamazepine-CR group) were included in the full analysis set for the primary analysis. Overall, 71.1% of eslicarbazepine acetate-treated patients and 75.6% of carbamazepine-CR-treated patients were seizure-free for ≥6 months at the last evaluated dose (average risk difference = -4.28%, 95% confidence interval [CI] = -10.30 to 1.74; relative risk difference = -5.87%, 95% CI = -13.50 to 2.44) in the per protocol set. Rates of treatment-emergent adverse events were similar between groups for patients in the safety set. Noninferiority was also demonstrated in the full analysis set, as 70.8% of patients with eslicarbazepine acetate and 74.0% with carbamazepine-CR were seizure-free at the last evaluated dose (average risk difference = -3.07, 95% CI = -9.04 to 2.89).
Treatment with eslicarbazepine acetate was noninferior to BID carbamazepine-CR. With its once-daily formulation, eslicarbazepine acetate provides a useful option for first-line monotherapy for adults with newly diagnosed epilepsy and focal onset seizures.
我们评估了每日一次的依沙佐双丙戊酸钠与每日两次（BID）卡马西平控释片（卡马西平-CR）单药治疗新诊断的局灶性癫痫患者的疗效和安全性。
这是一项随机、双盲、非劣效性试验（NCT01162460），采用逐步设计，有 3 个剂量水平。在 26 周评估期间无癫痫发作的患者（A 级：依沙佐双丙戊酸钠 800mg/卡马西平-CR 200mg BID）进入 6 个月的维持期。如果在评估期间发生癫痫发作，患者将滴定至下一个目标剂量（B 级：依沙佐双丙戊酸钠 1200mg/卡马西平-CR 400mg BID，C 级：依沙佐双丙戊酸钠 1600mg/卡马西平-CR 600mg BID），然后再次开始评估期。主要终点是在方案设定中稳定后 6 个月内无癫痫发作患者的比例。预设的非劣效性标准为治疗组之间 -12%的绝对差异和 -20%的相对差异。
共纳入 815 例患者，785 例（依沙佐双丙戊酸钠组 388 例，卡马西平-CR 组 397 例）纳入方案设定，785 例（依沙佐双丙戊酸钠组 401 例，卡马西平-CR 组 412 例）纳入主要分析的全分析集。总体而言，在最后评估剂量时，依沙佐双丙戊酸钠治疗组 71.1%和卡马西平-CR 治疗组 75.6%的患者癫痫无发作≥6 个月（平均风险差异=-4.28%，95%置信区间[CI]为-10.30 至 1.74；相对风险差异=-5.87%，95%CI 为-13.50 至 2.44）。在安全性组中，两组患者的治疗中出现的不良事件发生率相似。在全分析集也显示了非劣效性，因为依沙佐双丙戊酸钠治疗组 70.8%的患者和卡马西平-CR 治疗组 74.0%的患者在最后评估剂量时无癫痫发作（平均风险差异=-3.07，95%CI=-9.04 至 2.89）。
依沙佐双丙戊酸钠的治疗与 BID 卡马西平-CR 相当。依沙佐双丙戊酸钠每日一次的制剂为新诊断为癫痫和局灶性发作的成人提供了一种有用的一线单药治疗选择。
