Abstract：
OBJECTIVE: To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice.
METHODS: Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs).
RESULTS: Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0-74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0-100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings.
CONCLUSIONS: In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile.
METHODS: Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs).
RESULTS: Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0-74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0-100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings.
CONCLUSIONS: In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile.
摘要：
目的：确定在常规临床实践中高度难治性局灶性癫痫患者队列中使用西诺比特的有效性和安全性。
方法：观察性，回顾性,在三个西班牙中心接受cenobamate的受试者的4期研究。主要终点是最后一次随访时的保留率。主要次要终点是3个月和最后一次随访时50%的应答者和无癫痫发作率。其他次要终点是全球临床印象改善（CGI-I）评分和治疗引起的不良事件（TEAE）。
结果：51例高度难治性局灶性癫痫患者，病程24.7年，十个以前尝试过的ASM，并纳入了23.5%的既往癫痫手术.末次随访保留率为80.4%。三个月局灶性癫痫发作的50％应答率为56.5％（每月减少51％，0-74.6；p<0.0001），双侧强直阵挛性癫痫发作为63.6％（每月中位数减少89％，0-100；p=0.022）。共有54.3%的受试者报告局灶性癫痫发作强度降低,和66％表现出临床上显著的满意度。Cenobamate允许伴随的ASM显着减少，尤其是钠通道阻滞剂。在43.1%的个体中报告了TEAE，85%的人解决或改善，没有新的安全性发现。
结论：在本分析中，根据标准的临床实践，使用西诺巴酯治疗的高度难治性局灶性癫痫患者，有证据表明癫痫发作的频率和强度都有很高的降低，具有可管理的安全性。
方法：观察性，回顾性,在三个西班牙中心接受cenobamate的受试者的4期研究。主要终点是最后一次随访时的保留率。主要次要终点是3个月和最后一次随访时50%的应答者和无癫痫发作率。其他次要终点是全球临床印象改善（CGI-I）评分和治疗引起的不良事件（TEAE）。
结果：51例高度难治性局灶性癫痫患者，病程24.7年，十个以前尝试过的ASM，并纳入了23.5%的既往癫痫手术.末次随访保留率为80.4%。三个月局灶性癫痫发作的50％应答率为56.5％（每月减少51％，0-74.6；p<0.0001），双侧强直阵挛性癫痫发作为63.6％（每月中位数减少89％，0-100；p=0.022）。共有54.3%的受试者报告局灶性癫痫发作强度降低,和66％表现出临床上显著的满意度。Cenobamate允许伴随的ASM显着减少，尤其是钠通道阻滞剂。在43.1%的个体中报告了TEAE，85%的人解决或改善，没有新的安全性发现。
结论：在本分析中，根据标准的临床实践，使用西诺巴酯治疗的高度难治性局灶性癫痫患者，有证据表明癫痫发作的频率和强度都有很高的降低，具有可管理的安全性。
