Department of Neurology, Beaumont Hospital, Dublin, Ireland.
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
Epilepsia. 2023 May;64(5):1225-1235. doi: 10.1111/epi.17549. Epub 2023 Feb 27.
Recent clinical trials have shown that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy (DRE). However, little is known about cenobamate's performance in highly active (≥20 seizures/month) and ultra-refractory focal epilepsy (≥6 failed epilepsy treatments, including antiseizure medications [ASMs], epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a "real-world" severe DRE cohort.
We conducted a single-center retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment-emergent adverse events, and adjustments to concomitant ASMs were analyzed.
Fifty-seven patients received cenobamate for at least 3 months (median duration, 11 months). The median cenobamate dose was 250 mg/day (range 75-350 mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra-refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75%-99% reduction in seizures (42.1% of cohort), and 16 had a 50%-74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic-clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ≥250 mg/day. Three-fourths of patients reported at least one side-effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ≥250 mg/day. Side-effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine, and perampanel.
Patients with highly active and ultra-refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250 mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.
最近的临床试验表明，依诺佐胺可显著改善局灶性发作耐药性癫痫（DRE）的癫痫发作控制。然而，对于依诺佐胺在高度活跃（≥20 次癫痫发作/月）和超难治性局灶性癫痫（≥6 种失败的癫痫治疗方法，包括抗癫痫药物[ASM]、癫痫手术和迷走神经刺激）中的表现知之甚少。在这里，我们研究了依诺佐胺在“真实世界”严重 DRE 患者中的疗效和耐受性。
我们对 2020 年 10 月至 2022 年 9 月期间接受依诺佐胺治疗的连续成年患者进行了单中心回顾性分析。所有患者均通过早期获取计划接受依诺佐胺治疗。分析了依诺佐胺的保留率、癫痫发作结局、治疗中出现的不良事件以及对伴随的 ASM 的调整。
57 名患者接受依诺佐胺治疗至少 3 个月（中位治疗时间 11 个月）。依诺佐胺的中位剂量为 250mg/天（范围 75-350mg）。基线人口统计学特征与高度活跃（中位癫痫发作频率 60 次/月）和超难治性癫痫（中位既往失败的 ASM 数量 9 种）一致。大多数（87.8%）患者有癫痫手术和/或迷走神经刺激史。6 名患者因疗效不佳和/或不良事件而停止依诺佐胺治疗。1 名患者因与依诺佐胺无关的因素死亡。在继续接受依诺佐胺治疗的患者中，3 名患者癫痫发作完全停止（占队列的 5.3%），24 名患者癫痫发作减少 75%-99%（占队列的 42.1%），16 名患者癫痫发作减少 50%-74%（占队列的 28.1%）。依诺佐胺使 55.6%（36/65）的局灶性到双侧强直阵挛性癫痫发作患者发作停止。在治疗有反应的患者中，67.4%（29/43）的患者接受了≥250mg/天的依诺佐胺剂量。四分之三的患者报告至少有一种副作用，最常见的是疲劳和嗜睡。不良事件最常出现在依诺佐胺剂量≥250mg/天。通过减少总体 ASM 负担（最常见的是氯巴占、埃斯利卡朋和吡仑帕奈），部分可以控制副作用。
高度活跃和超难治性局灶性癫痫患者在依诺佐胺治疗中获得了有意义的癫痫发作结局。在 250mg/天以上剂量出现不良事件可能会限制依诺佐胺剂量更高时对癫痫发作控制的进一步改善。
