Comprehensive Epilepsy Care Center for Children and Adults, St. Louis, MO, USA.
SK Life Science, Inc, Paramus, NJ, USA.
Epilepsy Res. 2022 Jul;183:106940. doi: 10.1016/j.eplepsyres.2022.106940. Epub 2022 May 5.
To report post-hoc efficacy data by focal seizure subtypes from 10 US study sites from a large, global, open-label, phase 3 study of adjunctive cenobamate.
Patients 18-70 years old with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals (target dose 200 mg/day). Further increases to 400 mg/day by 50-mg/day increments every other week were allowed.
240 patients were evaluated; 27 (11.3%), 224 (93.3%), and 56 (23.3%) patients had focal aware motor (FAM), focal impaired awareness (FIA), and focal to bilateral tonic-clonic (FBTC) seizures, respectively (patients may have had ≥ 1 seizure subtype). Median baseline seizure frequencies/28 days were 10.5, 2.3, and 0.9 for FAM, FIA, and FBTC seizure subtypes. Reductions in median percent seizure frequency/28 days from baseline were observed during Months 1-3 (55.0%, 52.4%, and 94.1% for FAM, FIA, and FBTC). Greater reductions were observed during Months 4-5 (88.2%, 81.0%, and 100%) and during Months 25-27 (98.1%, 100%, and 100%). The percentage of patients achieving 100% seizure reduction in the FAM, FIA, and FBTC seizure subtypes was 22.2% (6/27), 21.5% (48/223), and 50% (28/56) during Months 1-3 and increased to 47.8% (11/23), 54.3% (88/162), and 90.5% (38/42) during Months 25-27, respectively. The most common treatment-emergent adverse events (≥ 20%) were fatigue, dizziness, and somnolence. No cases of DRESS were reported.
Seizure reductions occurred in all focal seizure subtypes with cenobamate over time through Months 25-27, with the earliest onset in the FBTC group. Results from this subset analysis of the phase 3 study support the long-term efficacy of cenobamate across focal seizure types.
报告来自 10 个美国研究地点的一项大型、全球性、开放性、3 期临床试验中附加用依佐加滨的局灶性癫痫发作亚组的事后疗效数据。
接受 1-3 种抗癫痫药物稳定剂量治疗且伴有未控制的局灶性癫痫发作的 18-70 岁患者，以 2 周间隔（目标剂量 200mg/天）递增日剂量（起始剂量 12.5、25、50、100、150、200mg/天）给予依佐加滨。允许每隔一周增加 50mg/天，进一步增加至 400mg/天。
评估了 240 例患者；27 例（11.3%）、224 例（93.3%）和 56 例（23.3%）患者分别有局灶性意识运动（FAM）、局灶性意识障碍（FIA）和局灶性双侧强直-阵挛（FBTC）发作（患者可能有≥1 种癫痫发作类型）。基线时 FAM、FIA 和 FBTC 发作类型的 28 天内中位癫痫发作频率分别为 10.5、2.3 和 0.9 次。在第 1-3 个月期间，观察到中位癫痫发作频率从基线降低了 55.0%、52.4%和 94.1%（FAM、FIA 和 FBTC）。在第 4-5 个月和第 25-27 个月期间观察到更大的降幅（88.2%、81.0%和 100%）。在第 1-3 个月期间，FAM、FIA 和 FBTC 发作类型中达到 100%癫痫发作减少的患者百分比分别为 22.2%（6/27）、21.5%（48/223）和 50%（28/56），在第 25-27 个月期间分别增加至 47.8%（11/23）、54.3%（88/162）和 90.5%（38/42）。最常见的治疗相关不良事件（≥20%）为疲劳、头晕和嗜睡。没有报告 DRESS 病例。
依佐加滨在第 1-3 个月内逐渐减少所有局灶性癫痫发作类型的癫痫发作，在 FBTC 组中最早出现。3 期研究的亚组分析结果支持依佐加滨在各种局灶性癫痫类型中的长期疗效。
