Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
West China Hospital, Sichuan, China.
CNS Neurosci Ther. 2021 Mar;27(3):330-340. doi: 10.1111/cns.13458.
This post hoc analysis assessed the efficacy and safety/tolerability of adjunctive perampanel in patients from China (aged ≥12 years) with focal seizures (FS), with/without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS).
Study centers in China were identified using data from five double-blind, randomized, phase III studies of adjunctive perampanel (2-12 mg/day) and their open-label extensions (OLEx). Efficacy assessments included median percent reduction in seizure frequency per 28 days, and 50% and 75% responder and seizure-freedom rates. Safety/tolerability assessments included monitoring of treatment-emergent adverse events (TEAEs).
Overall, 277 patients (placebo, n = 79; perampanel, n = 198) were included in the double-blind safety analysis set. The full analysis set comprised 274 patients (FS, n = 238 [placebo, n = 60; perampanel, n = 178]; FBTCS, n = 120 [placebo, n = 31; perampanel, n = 89]; GTCS, n = 36 [placebo, n = 18; perampanel, n = 18]). Median percent reductions in seizure frequency for placebo vs perampanel were as follows: 16.6% vs 32.4% (FS; P < 0.05) and 39.1% vs 48.2% (FBTCS; not significant [NS]) at 4-12 mg/day, and 37.9% vs 82.6% (GTCS; NS) at 8 mg/day; 50% responder rates were 31.7% vs 37.4% (FS; NS), 48.4% vs 51.9% (FBTCS; NS), and 33.3% vs 61.1% (GTCS; NS), respectively. Seizure-freedom rates were 1.7% vs 9.2%, 16.1% vs 25.3%, and 16.7% vs 44.4%, respectively (all NS). Overall, 262 patients entered the OLEx (FS, n = 228; GTCS, n = 34). Perampanel was efficacious for up to four years for FS and FBTCS and up to two years for GTCS. Across the double-blind and OLEx studies, TEAEs were reported in 65.7% and 81.3% of perampanel-treated patients, respectively; the most common was dizziness. Efficacy and safety/tolerability outcomes were generally similar between Chinese and non-Chinese patients.
Adjunctive perampanel (up to 12 mg/day) may be a suitable treatment for Chinese patients with FS, with/without FBTCS, or GTCS, with similar efficacy and safety/tolerability compared to non-Chinese patients.
本事后分析评估了在中国（年龄≥12 岁）局灶性发作（FS）、有/无局灶性到双侧强直阵挛发作（FBTCS）或全面强直阵挛发作（GTCS）的患者中，添加性吡仑帕奈的疗效和安全性/耐受性。
使用五项添加性吡仑帕奈（2-12mg/天）双盲、随机、III 期研究及其开放标签扩展（OLEx）的数据，确定中国的研究中心。疗效评估包括每 28 天的癫痫发作频率中位数降低百分比，以及 50%和 75%的应答者和无癫痫发作率。安全性/耐受性评估包括监测治疗出现的不良事件（TEAEs）。
总体而言，277 名患者（安慰剂，n=79；吡仑帕奈，n=198）被纳入双盲安全性分析集。全分析集包括 274 名患者（FS，n=238[安慰剂，n=60；吡仑帕奈，n=178]；FBTCS，n=120[安慰剂，n=31；吡仑帕奈，n=89]；GTCS，n=36[安慰剂，n=18；吡仑帕奈，n=18]）。安慰剂与吡仑帕奈的癫痫发作频率中位数降低百分比分别为：16.6%与 32.4%（FS；P<0.05）和 39.1%与 48.2%（FBTCS；无显著差异[NS]），在 4-12mg/天，和 37.9%与 82.6%（GTCS；NS）在 8mg/天；50%的应答率分别为 31.7%与 37.4%（FS；NS）、48.4%与 51.9%（FBTCS；NS）和 33.3%与 61.1%（GTCS；NS）。无癫痫发作率分别为 1.7%与 9.2%、16.1%与 25.3%和 16.7%与 44.4%（均 NS）。总体而言，262 名患者进入 OLEx（FS，n=228；GTCS，n=34）。吡仑帕奈对 FS 和 FBTCS 的疗效最长可达四年，对 GTCS 的疗效最长可达两年。在双盲和 OLEx 研究中，分别有 65.7%和 81.3%的吡仑帕奈治疗患者报告了 TEAEs；最常见的是头晕。疗效和安全性/耐受性结果在中、非中国患者之间通常相似。
添加性吡仑帕奈（最高 12mg/天）可能是中国 FS 伴/不伴 FBTCS 或 GTCS 患者的一种合适治疗方法，与非中国患者相比，具有相似的疗效和安全性/耐受性。
