先前抗癫痫药物数量对附加使用布瓦西坦控制局灶性发作效果和耐受性的影响：事后分析。
Effect of Number of Previous Antiseizure Medications on Efficacy and Tolerability of Adjunctive Brivaracetam for Uncontrolled Focal Seizures: Post Hoc Analysis.
机构信息
Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-Gu, Seoul, 03080, South Korea.
Department of Neurology, Yonsei University College of Medicine, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
出版信息
Adv Ther. 2021 Jul;38(7):4082-4099. doi: 10.1007/s12325-021-01816-5. Epub 2021 Jun 21.
INTRODUCTION
The aim was to evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with severely drug-resistant focal seizures versus adults with less drug-resistant disease.
METHODS
Data were pooled from patients with focal seizures on 1-2 concomitant antiseizure medications (ASMs) randomized to BRV 50, 100, 200 mg/day, or placebo in 3 phase 3 trials (N01252 [NCT00490035], N01253 [NCT00464269], and N01358 [NCT01261325]) with a 12-week treatment period. Outcomes were assessed in patients with ≥ 5 and 0-4 previous ASMs (stopped before trial drug initiation).
RESULTS
In ≥ 5 previous ASMs subgroup (BRV 50, 100, 200 mg/day: n = 26, n = 137, n = 120; placebo: n = 151), percentage reduction over placebo in 28-day adjusted focal seizure frequency was 13.0% for 50 mg/day (p = 0.38), 18.1% for 100 mg/day (p = 0.006), 19.8% for 200 mg/day (p = 0.004), and 17.0% for all BRV-treated patients (p = 0.001). The 50% responder rate was 26.9%, 29.9%, 30.0%, and 29.7% for BRV 50, 100, 200, and 50-200 mg/day, respectively (placebo: 13.2%); odds ratios versus placebo were statistically significant (p < 0.05) for BRV 100, 200, and 50-200 mg/day. In 0-4 previous ASMs subgroup (BRV 50, 100, 200 mg/day: n = 135, n = 195, n = 129; placebo: n = 267), all BRV dosages showed statistically significant (1) percentage reduction over placebo in 28-day adjusted focal seizure frequency (21.4-28.7%); (2) differences from placebo in median percentage reduction in 28-day adjusted focal seizure frequency from baseline (35.5-45.9%; placebo: 21.3%); and (3) odds ratios versus placebo (favoring BRV) for 50% responder rates. In BRV-treated patients, treatment-emergent adverse event (TEAE) incidence (73.8% [217/294] vs. 64.6% [329/509]) and discontinuation due to TEAEs (10.5% vs. 4.5%) were higher in the ≥ 5 versus 0-4 previous ASMs subgroup; serious TEAEs were rare in both subgroups (≥ 5 previous ASMs: 3.1%; 0-4 previous ASMs: 2.9%).
CONCLUSION
Adjunctive BRV showed efficacy and was generally well tolerated in adults with focal seizures independent of the number of previous ASMs.
简介
本研究旨在评估辅助使用溴维曲坦（BRV）治疗药物反应严重的局灶性癫痫成人患者（n=50、100、200mg/天）与药物反应较轻的患者（n=137、120）的疗效和耐受性。
方法
共有来自 3 项 3 期临床试验（N01252[NCT00490035]、N01253[NCT00464269]和 N01358[NCT01261325]）的患者纳入研究，这些患者正在服用 1-2 种抗癫痫药物，随机接受 BRV 50、100、200mg/天或安慰剂治疗，疗程 12 周。评估在有≥5 次（BRV 50、100、200mg/天：n=26，n=137，n=120；安慰剂：n=151）和 0-4 次（BRV 50、100、200mg/天：n=135，n=195，n=129；安慰剂：n=267）抗癫痫药物治疗史的患者中，28 天调整后的局灶性癫痫发作频率相对于安慰剂的降低百分比。
结果
在有≥5 次抗癫痫药物治疗史的患者亚组中，BRV 50、100、200mg/天组的 28 天调整后局灶性癫痫发作频率相对于安慰剂的降低百分比分别为 13.0%（p=0.38）、18.1%（p=0.006）、19.8%（p=0.004）和 17.0%（p=0.001）；BRV 所有治疗组的 50%应答率分别为 26.9%、29.9%、30.0%和 29.7%（安慰剂：13.2%），BRV 100、200 和 50-200mg/天的比值比与安慰剂相比均有统计学意义（p<0.05）。在有 0-4 次抗癫痫药物治疗史的患者亚组中，BRV 50、100、200mg/天组的 28 天调整后局灶性癫痫发作频率相对于安慰剂的降低百分比分别为 21.4%（p<0.001）、28.7%（p<0.001）、21.4%（p<0.001）；从基线到 28 天调整后局灶性癫痫发作频率的中位数降低百分比（35.5%-45.9%；安慰剂：21.3%）；BRV 50%应答率的比值比（有利于 BRV）。在 BRV 治疗患者中，治疗期不良事件（TEAE）发生率（73.8%[217/294]vs.64.6%[329/509]）和因 TEAEs 而停药（10.5%vs.4.5%）在有≥5 次与 0-4 次抗癫痫药物治疗史的患者亚组中较高；两个亚组均很少发生严重 TEAEs（≥5 次抗癫痫药物治疗史：3.1%；0-4 次抗癫痫药物治疗史：2.9%）。
结论
辅助使用溴维曲坦治疗局灶性癫痫成人患者，不论抗癫痫药物治疗史的数量如何，均具有疗效且总体耐受性良好。
Zotero 插件