Asadi-Pooya Ali A, Sperling Michael R, Chung Steve, Klein Pavel, Diaz Anyzeila, Elmoufti Sami, Schiemann Jimmy, Whitesides John
Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
Epilepsy Res. 2017 Mar;131:70-75. doi: 10.1016/j.eplepsyres.2017.02.007. Epub 2017 Feb 27.
Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV at enrollment were excluded from this analysis. Patients were categorized by their status of prior exposure to LEV, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LTG), to investigate any consistent trend towards reduced response in AED-exposed subgroups compared to AED-naïve subgroups, regardless of the mechanism of action. Study completion rates, percent reduction from baseline in focal seizure frequency over placebo, ≥50% responder rates, and tolerability were evaluated for each subgroup. A total of 1160 patients were investigated. Study completion rates were similar in the AED-exposed subgroups and AED-naïve subgroups. In subgroups with (531 patients) or without (629 patients) prior LEV exposure, ≥50% responder rates for each dose of BRV compared with placebo were generally higher among the LEV-naïve subgroups than the previously LEV-exposed subgroups. LEV-exposed subgroups receiving BRV doses ≥50mg/day showed greater ≥50% responder rates than those receiving placebo. Similar results were observed for CBZ, TPM, and LTG. Previous treatment failure with commonly prescribed AEDs (LEV, CBZ, TPM, or LTG) is associated with a reduced response to BRV irrespective of the mechanism of action. Hence, this post-hoc analysis indicates that previous treatment failure with LEV does not preclude the use of BRV in patients with epilepsy.
布立西坦（BRV）是一种针对突触小泡蛋白2A的选择性、高亲和力配体，是一种用于辅助治疗成年癫痫患者局灶性（部分性发作）癫痫的新型抗癫痫药物（AED）。进行这项事后分析旨在探讨辅助使用BRV在曾使用左乙拉西坦（LEV）的患者中的疗效，以及疗效变化是否与这两种药物相似的作用机制有关。数据来自三项III期研究（NCT00490035；NCT00464269；NCT01261325），研究对象为患有局灶性癫痫发作的成年人，他们服用1 - 2种抗癫痫药物，在12周的治疗期内接受安慰剂或每天50 - 200mg的BRV且未进行滴定。入组时正在服用LEV的患者被排除在该分析之外。根据患者既往接触LEV、卡马西平（CBZ）、托吡酯（TPM）或拉莫三嗪（LTG）的情况进行分类，以研究与未接触过抗癫痫药物的亚组相比，接触过抗癫痫药物的亚组中是否存在任何一致的反应降低趋势，而不考虑作用机制。对每个亚组评估研究完成率、与安慰剂相比局灶性癫痫发作频率从基线降低的百分比、≥50%反应者率和耐受性。总共调查了1160名患者。接触过抗癫痫药物的亚组和未接触过抗癫痫药物的亚组的研究完成率相似。在有（531例患者）或无（629例患者）既往LEV接触史的亚组中，与安慰剂相比，每个BRV剂量的≥50%反应者率在未接触过LEV的亚组中通常高于既往接触过LEV的亚组。接受≥50mg/天BRV剂量的既往接触过LEV的亚组显示出比接受安慰剂的亚组更高的≥50%反应者率。对于CBZ、TPM和LTG也观察到了类似结果。既往使用常用抗癫痫药物（LEV、CBZ、TPM或LTG）治疗失败与对BRV的反应降低相关，而不考虑作用机制。因此，这项事后分析表明，既往LEV治疗失败并不排除在癫痫患者中使用BRV。
