Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：比较疗效，安全,和其他较新的抗癫痫药物（ASM），包括brivaracetam的耐受性，艾司利卡西平,拉科沙胺,Perampanel,和唑尼沙胺，批准用于成人癫痫患者的耐药性局灶性发作性癫痫发作（FOS）的辅助治疗。
方法：进行系统文献综述（SLR）以获得相关疗效，安全,ASM治疗耐药FOS的耐受性数据。所有研究均全面评估异质性的潜在来源，并通过贝叶斯网络荟萃分析（NMA）进行分析。在维持期内，疗效结果为≥50%的应答率和癫痫发作自由度，使用多项贝叶斯NMA同时建模。安全性和耐受性结果是经历至少一个治疗紧急不良事件(TEAE)的患者比例和经历至少一个导致停药的TEAE的患者比例。
结果：SLR确定了76项研究，其中23个被包括在贝叶斯NMA中。与所有分析的ASM相比，Cenobamate在≥50％的应答率和癫痫发作自由结局方面具有统计学意义的较高比率。点估计表明，与布立拉西坦相比，西诺巴特与经历至少一种TEAE和至少一种TEAE导致停药的更高比率相关。拉科沙胺,和唑尼沙胺；然而，结果无统计学意义.
结论：与所有分析的ASM相比，赛诺巴米特与疗效增加相关。安全性和耐受性结果没有统计学上的显着差异。提出的结果证实了从以前发表的NMA得出的结论，与其他ASM相比，这也突出了西诺坦的显着功效。
方法：进行系统文献综述（SLR）以获得相关疗效，安全,ASM治疗耐药FOS的耐受性数据。所有研究均全面评估异质性的潜在来源，并通过贝叶斯网络荟萃分析（NMA）进行分析。在维持期内，疗效结果为≥50%的应答率和癫痫发作自由度，使用多项贝叶斯NMA同时建模。安全性和耐受性结果是经历至少一个治疗紧急不良事件(TEAE)的患者比例和经历至少一个导致停药的TEAE的患者比例。
结果：SLR确定了76项研究，其中23个被包括在贝叶斯NMA中。与所有分析的ASM相比，Cenobamate在≥50％的应答率和癫痫发作自由结局方面具有统计学意义的较高比率。点估计表明，与布立拉西坦相比，西诺巴特与经历至少一种TEAE和至少一种TEAE导致停药的更高比率相关。拉科沙胺,和唑尼沙胺；然而，结果无统计学意义.
结论：与所有分析的ASM相比，赛诺巴米特与疗效增加相关。安全性和耐受性结果没有统计学上的显着差异。提出的结果证实了从以前发表的NMA得出的结论，与其他ASM相比，这也突出了西诺坦的显着功效。
