Lagae Lieven, Klotz Kerstin Alexandra, Fogarasi András, Floricel Florin, Reichel Christoph, Elshoff Jan-Peer, Fleyshman Sofia, Kang Harriet
Department of Development and Regeneration, Pediatric Neurology Section, University Hospitals Katholieke Universiteit Leuven, Leuven, Belgium.
Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany.
Epilepsia. 2023 Nov;64(11):2934-2946. doi: 10.1111/epi.17754. Epub 2023 Sep 5.
This study was undertaken to evaluate the long-term safety, tolerability, and efficacy of adjunctive brivaracetam (BRV) treatment in pediatric patients with epilepsy.
A phase 3, open-label, multicenter, long-term follow-up trial (N01266; NCT01364597) was conducted on patients (aged 1 month to <17 years at core trial entry; direct enrollers aged 4 to <17 years) treated with BRV. Outcomes included treatment-emergent adverse events (TEAEs), behavior assessments (Achenbach Child Behavior Checklist [CBCL], Behavior Rating Inventory of Executive Function [BRIEF]/BRIEF-Preschool version [BRIEF-P]), and efficacy outcomes (percent change in focal seizure frequency, 50% responder rate for all seizure types for patient subgroups <2 years and ≥2 years of age using daily record card data).
Of 257 patients with ≥1 dose of BRV (141 [54.9%] male; mean age = 8.0 years [SD = 4.5]), 36 patients were <2 years of age, and 72.0% of patients had a history of focal seizures. Mean BRV exposure was 3.2 patient-years. At least one TEAE occurred in 93.4% patients, and 32.3% had serious TEAEs. Seven patients died during the trial; no deaths were considered treatment-related. Patients ≥2 years of age had a median decrease in 28-day adjusted focal seizure frequency of 62.9%, and 50.9% had a ≥50% response in all seizures. Patients <2 years of age had a median decrease in 28-day adjusted focal seizure frequency of 96.9%, and 68.2% had a ≥50% response in all seizures. Kaplan-Meier estimated treatment retention was 72.7%, 64.5%, 57.8%, 53.3%, 50.1%, and 44.8% at 1, 2, 3, 4, 5, and 6 years, respectively. Mean changes (baseline to last evaluation) for all Achenbach CBCL and BRIEF-P/BRIEF subscale scores were negative, reflecting stability/slight improvement.
Long-term adjunctive BRV treatment was generally well tolerated and efficacious in reducing seizure frequency, and had high retention rates, with generally stable cognitive/behavioral scores in pediatric patients with epilepsy.
本研究旨在评估辅助使用布瓦西坦（BRV）治疗癫痫患儿的长期安全性、耐受性和疗效。
对接受BRV治疗的患者（核心试验入组时年龄为1个月至<17岁；直接入组者年龄为4至<17岁）进行了一项3期、开放标签、多中心、长期随访试验（N01266；NCT01364597）。观察指标包括治疗中出现的不良事件（TEAE）、行为评估（阿肯巴克儿童行为量表 [CBCL]、执行功能行为评定量表 [BRIEF]/学前版 [BRIEF-P]）以及疗效指标（局灶性癫痫发作频率的百分比变化，使用每日记录卡数据，对年龄<2岁和≥2岁的患者亚组所有癫痫发作类型的50%缓解率）。
257例接受≥1剂BRV治疗的患者中（141例 [54.9%] 为男性；平均年龄 = 8.0岁 [标准差 = 4.5]），36例患者年龄<2岁，72.0%的患者有局灶性癫痫发作史。BRV的平均暴露时间为3.2患者年。93.4%的患者发生了至少1次TEAE，32.3%的患者发生了严重TEAE。7例患者在试验期间死亡；无死亡被认为与治疗相关。≥2岁的患者28天调整后的局灶性癫痫发作频率中位数下降了62.9%，50.9%的患者所有癫痫发作有≥50%的缓解。<2岁的患者28天调整后的局灶性癫痫发作频率中位数下降了96.9%，68.2%的患者所有癫痫发作有≥50%的缓解。Kaplan-Meier估计的治疗保留率在1、2、3、4、5和6年时分别为72.7%、64.5%、57.8%、53.3%、50.1%和44.8%。所有阿肯巴克CBCL和BRIEF-P/BRIEF子量表评分从基线到最后评估的平均变化均为负数，反映出稳定性/略有改善。
长期辅助使用BRV治疗通常耐受性良好，在降低癫痫发作频率方面有效，保留率高，癫痫患儿的认知/行为评分总体稳定。
