在中国使用左乙拉西坦和卡马西平单药治疗部分性癫痫发作的比较:一项开放性、非劣效性试验的主要结果  

Comparison of levetiracetam and carbamazepine monotherapy for focal seizures in China:primary results of an open-label,noninferiority trial

作　　者：廖卫平[1] 周东[2] Toru Osakabe Christian Loesch 杜新鲁 Frank Tennigkeit 王学峰[6] LIAO Wei-ping;ZHOU Dong;Toru Osakabe(Department of Neurology,the Second Afiliated Hospital of Guangzhou Medical University,Grangzhou 510260,China)

机构地区：[1]广州医科大学附属第二医院神经内科,510260 [2]四川大学华西医院神经内科 [3]日本东京UCB Pharma [4]德国蒙海姆UCB Pharma [5]中国香港UCB Pharma [6]重庆医科大学附属第一医院神经内科

出　　处：《临床神经病学杂志》2020年第5期321-327,共7页Journal of Clinical Neurology

基　　金：UCB Pharma资助

摘　　要：目的针对≥16岁、新诊断或最近诊断为部分性癫痫发作的中国患者,比较左乙拉西坦和速释卡马西平(CBZ-IR)单药治疗的疗效。方法在Ⅲ期、随机分配、开放性试验N01364(NCT01954121)中,患者按1∶1的比例随机分配接受左乙拉西坦1 000 mg/d或CBZ-IR 400 mg/d,记录6个月无癫痫发作的患者比例及患者保留率、首次癫痫发作的时间、因不良事件或缺乏疗效导致首次癫痫发作/中止试验的时间、安全性和耐受性。结果在对符合方案集进行的分析中,接受左乙拉西坦治疗的186例患者中有88例(47.3%),接受CBZ-IR治疗的171例患者中有117例(68.4%)达到6个月无癫痫发作;校正后绝对差值为-22.9%(95%CI:-33.1%,-12.6%),其下限低于非劣效性界值-20%。左乙拉西坦组的患者保留率为48.4%,CBZ-IR组为70.2%。对于评估期首次癫痫发作时间,左乙拉西坦与CBZ-IR的风险比为2.686(95%CI:1.838,3.927);对于因不良事件或缺乏疗效导致首次癫痫发作/中止试验的时间,风险比为2.338(95%CI:1.629, 3.356)。使用左乙拉西坦在治疗中出现的不良事件(61.9%)略低于CBZ-IR(67.9%)。结论在低剂量单药治疗下,无法确定左乙拉西坦的疗效不低于CBZ-IR。左乙拉西坦的安全性/耐受性情况优于CBZ-IR。Objective To compare levetiracetam and immediate-release carbamazepine(CBZ-IR) as monotherapy for Chinese patients aged ≥16 years with newly or recently diagnosed focal seizures. Methods In the Phase Ⅲ, randomized, open-label trial N01364(NCT01954121), patients were randomized 1∶1 to levetiracetam 1 000 mg/d or CBZ-IR 400 mg/d. The percentage of patients achieving 6-month seizure freedom was recorded. So did the time to first seizure, and time to first seizure/discontinuation due to adverse events or lack of efficacy. And the safety/tolerability was also evaluated. Results In the Per-Protocol Set analysis, 88/186(47.3%) levetiracetam-treated patients and 117/171(68.4%) CBZ-IR-treated patients achieved 6-month seizure freedom. The adjusted absolute difference was-22.9%(95%CI:-33.1%,-12.6%), the lower bound of which was below the-20% noninferiority threshold. Retention was 48.4% for levetiracetam group and 70.2% for CBZ-IR group. The hazard ratio of levetiracetam versus CBZ-IR was 2.686(95%CI: 1.838, 3.927) for time to first seizure and 2.338(95%CI: 1.629, 3.356) for time to first seizure/discontinuation due to adverse events or lack of efficacy. Treatment-emergent adverse event incidence was slightly lower with levetiracetam(61.9%) versus CBZ-IR(67.9%). Conclusions Noninferiority of levetiracetam versus CBZ-IR could not be established as low-dose monotherapy. Levetiracetam showed a favorable safety/tolerability profile versus CBZ-IR.

关 键 词：卡马西平 疗效 部分性癫痫发作 左乙拉西坦 安全性/耐受性 

分 类 号：R742.1[医药卫生—神经病学与精神病学]