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Abstract：
BACKGROUND: This article aimed to assess the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with focal-onset seizures on specific concomitant antiseizure medications (ASMs) taken as part of their treatment regimen.
METHODS: This was a post hoc analysis of pooled data from double-blind, placebo-controlled trials (N01252/NCT00490035, N01253/NCT00464269, and N01358/NCT01261325) in patients with uncontrolled focal-onset seizures randomized to BRV (50-200 mg/day) or placebo on the most common concomitant ASMs at trial initiation.
RESULTS: Nine concomitant ASMs were analyzed: carbamazepine (CBZ), lamotrigine (LTG), valproate (VPA), oxcarbazepine (OXC), topiramate (TPM), phenytoin (PHT), lacosamide (LCM), clobazam (CLB), and phenobarbital (PHB). Reduction over placebo in focal-onset seizure frequency per 28 days with BRV ranged from 11.7% (concomitant OXC) to 33.5% (concomitant PHB). The median percentage reduction from baseline in focal-onset seizure frequency per 28 days ranged from 25.5% to 42.8% in patients on BRV (placebo 4.4-21.2%); 50% responder rates ranged from 31.9% to 44.9% in patients on BRV (placebo 11.4-25.2%). In patients on BRV, seizure freedom ranged from 1.4% (concomitant PHT) to 12.5% (concomitant LCM); seizure freedom ranged from 0% to 1.2% in patients on placebo. All efficacy endpoints analyzed were consistently numerically higher in patients on BRV versus placebo. The overall incidence of treatment-emergent adverse events (TEAEs) was generally similar across subgroups by specific concomitant ASMs in patients on BRV (range 60.8-74.5%) or placebo (range 53.8-66.7%). Drug-related TEAEs were numerically higher across all subgroups by concomitant ASM in patients on BRV (range 35.2-48.3%) versus placebo (range 23.9-37.1%). Discontinuations due to TEAEs ranged from 2.9% to 13.3% in patients on BRV and was 0-5.7% for patients taking placebo across subgroups.
CONCLUSIONS: BRV was efficacious and well tolerated regardless of the specific concomitant ASMs used as part of their treatment regimen. These data show that in patients with focal-onset seizures, BRV provides additional efficacy to a broad range of ASMs.
METHODS: This was a post hoc analysis of pooled data from double-blind, placebo-controlled trials (N01252/NCT00490035, N01253/NCT00464269, and N01358/NCT01261325) in patients with uncontrolled focal-onset seizures randomized to BRV (50-200 mg/day) or placebo on the most common concomitant ASMs at trial initiation.
RESULTS: Nine concomitant ASMs were analyzed: carbamazepine (CBZ), lamotrigine (LTG), valproate (VPA), oxcarbazepine (OXC), topiramate (TPM), phenytoin (PHT), lacosamide (LCM), clobazam (CLB), and phenobarbital (PHB). Reduction over placebo in focal-onset seizure frequency per 28 days with BRV ranged from 11.7% (concomitant OXC) to 33.5% (concomitant PHB). The median percentage reduction from baseline in focal-onset seizure frequency per 28 days ranged from 25.5% to 42.8% in patients on BRV (placebo 4.4-21.2%); 50% responder rates ranged from 31.9% to 44.9% in patients on BRV (placebo 11.4-25.2%). In patients on BRV, seizure freedom ranged from 1.4% (concomitant PHT) to 12.5% (concomitant LCM); seizure freedom ranged from 0% to 1.2% in patients on placebo. All efficacy endpoints analyzed were consistently numerically higher in patients on BRV versus placebo. The overall incidence of treatment-emergent adverse events (TEAEs) was generally similar across subgroups by specific concomitant ASMs in patients on BRV (range 60.8-74.5%) or placebo (range 53.8-66.7%). Drug-related TEAEs were numerically higher across all subgroups by concomitant ASM in patients on BRV (range 35.2-48.3%) versus placebo (range 23.9-37.1%). Discontinuations due to TEAEs ranged from 2.9% to 13.3% in patients on BRV and was 0-5.7% for patients taking placebo across subgroups.
CONCLUSIONS: BRV was efficacious and well tolerated regardless of the specific concomitant ASMs used as part of their treatment regimen. These data show that in patients with focal-onset seizures, BRV provides additional efficacy to a broad range of ASMs.
摘要：
背景：本文旨在评估辅助布立西坦（BRV）在局灶性发作性癫痫发作的成年人中的疗效和耐受性，这些药物作为治疗方案的一部分服用特定的合并抗癫痫药物（ASM）。
方法：这是对来自双盲的汇总数据的事后分析，安慰剂对照试验(N01252/NCT00490035,N01253/NCT00464269和N01358/NCT01261325)在试验开始时随机接受BRV(50-200mg/day)或安慰剂治疗的非受控局灶性发作性癫痫患者中进行随机治疗。
结果：分析了9个伴随的ASM：卡马西平（CBZ），拉莫三嗪(LTG),丙戊酸盐(VPA),奥卡西平（OXC），托吡酯(TPM),苯妥英(PHT),拉科沙胺(LCM),clobazam（CLB），和苯巴比妥（PHB）。与安慰剂相比，每28天BRV的局灶性发作发作发作频率的降低范围为11.7％（伴随的OXC）至33.5％（伴随的PHB）。BRV患者（安慰剂4.4-21.2％），每28天局灶性发作发作频率从基线降低的中位数百分比为25.5％至42.8％；BRV患者（安慰剂11.4-25.2％）的50％应答率范围为31.9％至44.9％。在BRV患者中，癫痫发作自由度为1.4%(伴随PHT)~12.5%(伴随LCM);安慰剂组患者的癫痫发作自由度为0%~1.2%.与安慰剂相比，BRV患者分析的所有疗效终点在数值上始终较高。在BRV（范围为60.8-74.5%）或安慰剂（范围为53.8-66.7%）的患者中，治疗引起的不良事件（TEAE）的总发生率在不同亚组之间通常相似。BRV患者（范围35.2-48.3％）与安慰剂（范围23.9-37.1％）伴随ASM在所有亚组中的药物相关TEAE数字上较高。在BRV患者中，由于TEAE引起的停药范围为2.9％至13.3％，在亚组中服用安慰剂的患者为0-5.7％。
结论：BRV有效且耐受性良好，无论作为其治疗方案的一部分的特定伴随ASM如何。这些数据表明，在局灶性癫痫发作的患者中，BRV为宽范围的ASM提供额外的功效。
方法：这是对来自双盲的汇总数据的事后分析，安慰剂对照试验(N01252/NCT00490035,N01253/NCT00464269和N01358/NCT01261325)在试验开始时随机接受BRV(50-200mg/day)或安慰剂治疗的非受控局灶性发作性癫痫患者中进行随机治疗。
结果：分析了9个伴随的ASM：卡马西平（CBZ），拉莫三嗪(LTG),丙戊酸盐(VPA),奥卡西平（OXC），托吡酯(TPM),苯妥英(PHT),拉科沙胺(LCM),clobazam（CLB），和苯巴比妥（PHB）。与安慰剂相比，每28天BRV的局灶性发作发作发作频率的降低范围为11.7％（伴随的OXC）至33.5％（伴随的PHB）。BRV患者（安慰剂4.4-21.2％），每28天局灶性发作发作频率从基线降低的中位数百分比为25.5％至42.8％；BRV患者（安慰剂11.4-25.2％）的50％应答率范围为31.9％至44.9％。在BRV患者中，癫痫发作自由度为1.4%(伴随PHT)~12.5%(伴随LCM);安慰剂组患者的癫痫发作自由度为0%~1.2%.与安慰剂相比，BRV患者分析的所有疗效终点在数值上始终较高。在BRV（范围为60.8-74.5%）或安慰剂（范围为53.8-66.7%）的患者中，治疗引起的不良事件（TEAE）的总发生率在不同亚组之间通常相似。BRV患者（范围35.2-48.3％）与安慰剂（范围23.9-37.1％）伴随ASM在所有亚组中的药物相关TEAE数字上较高。在BRV患者中，由于TEAE引起的停药范围为2.9％至13.3％，在亚组中服用安慰剂的患者为0-5.7％。
结论：BRV有效且耐受性良好，无论作为其治疗方案的一部分的特定伴随ASM如何。这些数据表明，在局灶性癫痫发作的患者中，BRV为宽范围的ASM提供额外的功效。
