Angelini Pharma UK-I, Napier House, 24 High Holborn, London WC1V 6AZ, UK.
Putnam Associates, LLC., Toronto, Canada.
Seizure. 2024 May;118:80-90. doi: 10.1016/j.seizure.2024.04.004. Epub 2024 Apr 5.
To compare the efficacy, safety, and tolerability of cenobamate with other newer anti-seizure medications (ASMs) including brivaracetam, eslicarbazepine, lacosamide, perampanel, and zonisamide, approved for adjunctive treatment of drug-resistant focal-onset seizures (FOS) in adults with epilepsy.
A systematic literature review (SLR) was conducted to obtain relevant efficacy, safety, and tolerability data for ASMs for the treatment of drug-resistant FOS. All studies were thoroughly assessed for potential sources of heterogeneity and analysed via Bayesian network meta-analyses (NMAs). Efficacy outcomes were ≥50 % responder rate and seizure freedom during the maintenance period, which were modelled simultaneously using a multinomial Bayesian NMA. Safety and tolerability outcomes were the proportion of patients who experienced at least one treatment-emergent adverse event (TEAE) and the proportion who experienced at least one TEAE leading to discontinuation.
The SLR identified 76 studies, of which 23 were included in the Bayesian NMAs. Cenobamate was associated with statistically significant higher rates for the ≥50 % responder rate and seizure freedom outcomes compared with all ASMs analysed. The point estimates indicated that cenobamate was associated with higher rates of experiencing at least one TEAE and at least one TEAE leading to discontinuation compared with brivaracetam, lacosamide, and zonisamide; however, no results were statistically significant.
Cenobamate was associated with increased efficacy compared with all ASMs analysed. There were no statistically significant differences in the safety and tolerability outcomes. The results presented corroborate the conclusions drawn from previous published NMAs, which also highlight the notable efficacy of cenobamate in comparison with other ASMs.
比较加巴喷丁、依佐加滨、拉科酰胺、吡仑帕奈和左乙拉西坦等新的抗癫痫药物(AEDs)与cenobamate 治疗成人耐药性局灶性癫痫发作(FOS)的疗效、安全性和耐受性,这些药物均被批准用于辅助治疗。
进行系统文献回顾(SLR)以获得 AEDs 治疗耐药性 FOS 的相关疗效、安全性和耐受性数据。对所有研究进行了彻底评估,以确定潜在的异质性来源,并通过贝叶斯网络荟萃分析(NMA)进行分析。疗效结局为维持期≥50%的应答率和无癫痫发作,使用多项贝叶斯 NMA 同时对其进行建模。安全性和耐受性结局为经历至少一次治疗相关不良事件(TEAE)和至少一次因 TEAE 而停药的患者比例。
SLR 确定了 76 项研究,其中 23 项研究被纳入贝叶斯 NMA。与分析的所有 AED 相比,cenobamate 与≥50%的应答率和无癫痫发作结局的发生率更高相关。点估计表明,与 brivaracetam、拉科酰胺和佐尼沙胺相比,cenobamate 与经历至少一次 TEAE 和至少一次因 TEAE 而停药的发生率更高;然而,没有结果具有统计学意义。
与分析的所有 AED 相比,cenobamate 具有更高的疗效。在安全性和耐受性结局方面无统计学差异。结果与之前发表的 NMA 得出的结论一致,这些结论也强调了 cenobamate 与其他 AEDs 相比具有显著的疗效。