Abstract：
BACKGROUND: Adjunctive cenobamate was effective and safe for the treatment of uncontrolled focal onset seizures in a randomized, double-blind, placebo-controlled, phase 2 study (YKP3089C017; NCT01866111). This post-hoc analysis assessed the efficacy of adjunctive cenobamate in the treatment of patients with different epileptic etiologies during the study.
METHODS: Adult patients with uncontrolled focal seizures who previously received 1 to 3 antiseizure medications (ASMs) were randomly assigned in a ratio of 1:1:1:1 to receive placebo or cenobamate 100, 200 or 400 mg/day. Patients were further stratified based on their etiologic causes as genetic/presumed genetic, unknown cause, structural cause, and not reported (NR) groups. The frequency per 28 days for an 18-week double-blind treatment period, responder rates (≥50 %, ≥75 %, ≥90 %, and 100 %) during the maintenance phase (12 weeks), and safety were assessed.
RESULTS: A total of 394 patients were categorized into the genetic/presumed genetic (n = 9; 2.28 %), unknown cause (n = 199; 50.51 %), structural cause (n = 177; 44.92 %), and NR (n = 13; 3.30 %) groups, with 4 patients were classified into either of the two etiological causes each. The baseline characteristics were comparable. The percentage of reduction in seizure frequency per 28 days was significantly higher in the cenobamate-treated structural (p = 0.01) and unknown cause (p = 0.0003) groups compared with the placebo group. Responder rates of ≥50 %, ≥75 %, ≥90 %, and 100 % were also higher with cenobamate therapy. Notably, no serious treatment-emergent adverse events (TEAEs) were observed in the genetic/presumed genetic group treated with cenobamate. The most common TEAEs (≥10 %) occurring in patients treated with cenobamate were nervous system disorders by system organ class, and somnolence was the most commonly reported TEAE.
CONCLUSIONS: Cenobamate reduces seizures in adult patients previously treated with ASMs, with high responder rates and acceptable safety, regardless of underlying causes.
METHODS: Adult patients with uncontrolled focal seizures who previously received 1 to 3 antiseizure medications (ASMs) were randomly assigned in a ratio of 1:1:1:1 to receive placebo or cenobamate 100, 200 or 400 mg/day. Patients were further stratified based on their etiologic causes as genetic/presumed genetic, unknown cause, structural cause, and not reported (NR) groups. The frequency per 28 days for an 18-week double-blind treatment period, responder rates (≥50 %, ≥75 %, ≥90 %, and 100 %) during the maintenance phase (12 weeks), and safety were assessed.
RESULTS: A total of 394 patients were categorized into the genetic/presumed genetic (n = 9; 2.28 %), unknown cause (n = 199; 50.51 %), structural cause (n = 177; 44.92 %), and NR (n = 13; 3.30 %) groups, with 4 patients were classified into either of the two etiological causes each. The baseline characteristics were comparable. The percentage of reduction in seizure frequency per 28 days was significantly higher in the cenobamate-treated structural (p = 0.01) and unknown cause (p = 0.0003) groups compared with the placebo group. Responder rates of ≥50 %, ≥75 %, ≥90 %, and 100 % were also higher with cenobamate therapy. Notably, no serious treatment-emergent adverse events (TEAEs) were observed in the genetic/presumed genetic group treated with cenobamate. The most common TEAEs (≥10 %) occurring in patients treated with cenobamate were nervous system disorders by system organ class, and somnolence was the most commonly reported TEAE.
CONCLUSIONS: Cenobamate reduces seizures in adult patients previously treated with ASMs, with high responder rates and acceptable safety, regardless of underlying causes.
摘要：
背景：在一项随机研究中，辅助cenobamate治疗不受控制的局灶性发作性癫痫发作是有效和安全的，双盲,安慰剂对照,2期研究（YKP3089C017；NCT01866111）。这项事后分析评估了在研究过程中，辅助性cenobamate治疗不同癫痫病因患者的疗效。
方法：先前接受过1-3种抗癫痫药物（ASM）的局灶性癫痫发作不受控制的成年患者，以1：1：1：1的比例随机分配接受安慰剂或西诺巴酯100、200或400mg/天。根据病因将患者进一步分层为遗传/假定遗传，不明原因,结构性原因，和未报告（NR）组。18周双盲治疗期每28天的频率，响应者比率(≥50%，≥75%,≥90%,和100%)在维护阶段(12周)，和安全性进行了评估。
结果：共有394名患者被归类为遗传/假定遗传（n=9；2.28％），不明原因（n=199；50.51%），结构性原因(n=177；44.92%)，和NR(n=13；3.30%)组，4例患者被分为两种病因之一。基线特征具有可比性。每28天癫痫发作频率减少的百分比显着高于安慰剂组（p=0.01）和未知原因组（p=0.0003）。应答率≥50%,≥75%,≥90%,和100％也更高与西尼obamate治疗。值得注意的是,在接受西尼obamate治疗的遗传/假定遗传组中未观察到严重的治疗引起的不良事件(TEAE).最常见的TEAEs（≥10％）发生在接受西诺膦酸治疗的患者中，是按系统器官类别划分的神经系统疾病，嗜睡是最常报道的TEAE。
结论：Cenobamate减少了先前接受ASM治疗的成年患者的癫痫发作，具有较高的响应率和可接受的安全性，不管潜在的原因。
方法：先前接受过1-3种抗癫痫药物（ASM）的局灶性癫痫发作不受控制的成年患者，以1：1：1：1的比例随机分配接受安慰剂或西诺巴酯100、200或400mg/天。根据病因将患者进一步分层为遗传/假定遗传，不明原因,结构性原因，和未报告（NR）组。18周双盲治疗期每28天的频率，响应者比率(≥50%，≥75%,≥90%,和100%)在维护阶段(12周)，和安全性进行了评估。
结果：共有394名患者被归类为遗传/假定遗传（n=9；2.28％），不明原因（n=199；50.51%），结构性原因(n=177；44.92%)，和NR(n=13；3.30%)组，4例患者被分为两种病因之一。基线特征具有可比性。每28天癫痫发作频率减少的百分比显着高于安慰剂组（p=0.01）和未知原因组（p=0.0003）。应答率≥50%,≥75%,≥90%,和100％也更高与西尼obamate治疗。值得注意的是,在接受西尼obamate治疗的遗传/假定遗传组中未观察到严重的治疗引起的不良事件(TEAE).最常见的TEAEs（≥10％）发生在接受西诺膦酸治疗的患者中，是按系统器官类别划分的神经系统疾病，嗜睡是最常报道的TEAE。
结论：Cenobamate减少了先前接受ASM治疗的成年患者的癫痫发作，具有较高的响应率和可接受的安全性，不管潜在的原因。
