Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca 71, 60020, Ancona, Italy.
Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria.
CNS Drugs. 2020 Nov;34(11):1105-1120. doi: 10.1007/s40263-020-00759-9.
Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. This drug can enhance the inactivated state of voltage-gated sodium channels, preferentially inhibiting the persistent component of the sodium channel current, and acts as a positive allosteric modulator of GABA receptors, binding at a non-benzodiazepine site.
We assessed the efficacy and safety of adjunctive cenobamate for the treatment of focal-onset seizures in adult patients with epilepsy using meta-analytical techniques.
We systematically searched (May, week 4, 2020) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ). There were no date limitations or language restrictions. Randomized, placebo-controlled, single or double-blinded, add-on trials of cenobamate in adult patients with uncontrolled focal-onset seizures were identified. Main outcomes included the proportion of patients with ≥ 50 and 100% reduction in seizure frequency during the maintenance treatment period compared with baseline and the incidence of treatment withdrawal and adverse events (AEs). Risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome.
Two trials were included, overall enrolling 659 patients (442 for the add-on cenobamate group and 217 for the add-on placebo group). Seizure frequency reduction by at least 50% occurred during the maintenance phase in 50.1% of the patients randomized to cenobamate and 23.5% of the placebo-treated participants (RR 2.18, 95% CI 1.67-2.85; p < 0.001). The pooled estimated RR to achieve seizure freedom for the cenobamate group in comparison with placebo was 3.71 (95% CI 1.93-7.14; p < 0.001). Withdrawal from randomized treatment occurred in 16.7 and 11.1% of participants receiving cenobamate and placebo, respectively (RR 1.34, 95% CI 0.85-2.09; p = 0.205). Treatment was discontinued due to AEs in 12.2 and 4.1% of the patients in the active and control arms (RR 2.27, 95% CI 1.08-4.79; p = 0.031). AEs were reported in 76.9 and 66.8% of the patients during treatment with cenobamate and placebo (RR 1.14, 95% CI 1.02-1.26; p = 0.021). The cenobamate-associated AEs included somnolence, dizziness, fatigue, balance disorder, and diplopia.
Adjunctive cenobamate in adult patients with uncontrolled focal-onset seizures is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo.
依诺巴比妥是一种新型的四唑衍生氨基甲酸酯化合物，具有双重作用机制。该药可增强电压门控钠通道的失活状态，优先抑制钠通道电流的持续成分，并作为 GABA 受体的正变构调节剂，结合在非苯二氮䓬结合位点。
我们使用荟萃分析技术评估了添加依诺巴比妥治疗成人癫痫局灶性发作的疗效和安全性。
我们系统地检索了（2020 年 5 月，第 4 周，星期四）MEDLINE（通过 PubMed 访问）、Cochrane 对照试验中心注册库（CENTRAL）和美国国立卫生研究院临床试验注册处（http://www.clinicaltrials.gov）。没有日期限制或语言限制。确定了成人局灶性发作性癫痫患者中添加依诺巴比妥的随机、安慰剂对照、单盲或双盲、附加试验。主要结局包括与基线相比，维持治疗期间至少减少 50%和 100%的发作频率的患者比例，以及治疗退出和不良事件（AE）的发生率。使用 95%置信区间（CI）的风险比（RR）来估计每个结局。
共纳入两项试验，共纳入 659 例患者（442 例接受附加依诺巴比妥治疗，217 例接受附加安慰剂治疗）。在维持阶段，50.1%的随机接受依诺巴比妥治疗的患者和 23.5%的安慰剂治疗患者的癫痫发作频率至少减少 50%（RR 2.18，95%CI 1.67-2.85；p<0.001）。与安慰剂相比，依诺巴比妥组达到无癫痫发作的估计 RR 为 3.71（95%CI 1.93-7.14；p<0.001）。分别有 16.7%和 11.1%的接受依诺巴比妥和安慰剂治疗的患者退出随机治疗（RR 1.34，95%CI 0.85-2.09；p=0.205）。因 AE 而停止治疗的患者分别为 12.2%和 4.1%（RR 2.27，95%CI 1.08-4.79；p=0.031）。依诺巴比妥组和安慰剂组分别有 76.9%和 66.8%的患者在治疗期间出现 AE（RR 1.14，95%CI 1.02-1.26；p=0.021）。依诺巴比妥相关 AE 包括嗜睡、头晕、疲劳、平衡障碍和复视。
在成人局灶性发作性癫痫患者中，添加依诺巴比妥可较安慰剂更显著地降低癫痫发作频率，且不良反应发生率更高。
