Long-term safety and efficacy of adjunctive lacosamide in the treatment of generalized onset tonic-clonic seizures: An open-label extension trial.

IF 6.6 1区医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2024-10-26 DOI:10.1111/epi.18158

David G Vossler, Mark Kristof Farkas, Irina Poverennova, Masako Watanabe, Peter Conrath, Svetlana Dimova, Carrie McClung, Robert Roebling, Paulette Williams, Terence J O'Brien

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Abstract

Objective: This study was undertaken to assess long-term safety, tolerability, and efficacy of lacosamide (LCM) as adjunctive therapy for generalized onset tonic-clonic seizures (GTCS) in patients aged ≥4 years with idiopathic generalized epilepsy (IGE).

Methods: EP0012 (NCT02408549) was a phase 3, multicenter, open-label extension (OLE) trial. Patients were enrolled from SP0982 (NCT02408523). Trial duration was ≥2 years (adults) and ≤5 years (children). The trial consisted of a treatment period, ≤4-week taper period, and 30-day safety follow-up. Safety (primary) variables were incidence of treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, incidence of onset of absence or myoclonic seizures, and increase in days with absence or myoclonic seizures per 28 days. Efficacy (secondary) variable was percent change in GTCS frequency per 28 days. Kaplan-Meier estimated retention rates and analyses by number of lifetime antiseizure medications (ASMs) were performed post hoc.

Results: Overall, 239 patients (mean age = 27.9 years, 56.1% female, 18.4% children) were enrolled and received ≥1 dose of LCM in this OLE (median treatment duration = 3.2 years); 157 (65.7%) completed the trial, and 82 (34.3%) discontinued. The most common reason for discontinuation (≥10%) was withdrawn consent (30 [12.6%]). Kaplan-Meier estimated retention rate was 87%, 72%, and 60% at 1, 3, and 5 years, respectively. Overall, 222 (92.9%) patients reported TEAEs; 19 (7.9%) discontinued due to TEAEs. Few patients had an increase in number of days with absence or myoclonic seizures, or incidence of new absence or myoclonic seizures. Median percent change in GTCS frequency per 28 days from the combined baseline was -88.6% (range = -100.0 to 465.4, n = 238). Post hoc analyses demonstrated small numerical differences between patients with 1, 2, and ≥3 lifetime ASMs.

Significance: The results support the use of long-term adjunctive LCM for GTCS in patients with IGE. Long-term adjunctive LCM was efficacious and well tolerated independent of the number of ASMs used before LCM initiation.

Clinical trial registration: ClinicalTrials.gov: NCT02408549.

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辅助拉科萨胺治疗全身强直阵挛发作的长期安全性和有效性：一项开放标签扩展试验。

研究目的本研究旨在评估拉科萨胺（LCM）作为特发性全身性癫痫（IGE）辅助疗法治疗年龄≥4岁的全身性强直-阵挛发作（GTCS）的长期安全性、耐受性和疗效：EP0012（NCT02408549）是一项3期、多中心、开放标签扩展（OLE）试验。患者从SP0982（NCT02408523）中招募。试验持续时间≥2年（成人）和≤5年（儿童）。试验包括治疗期、≤4 周的减量期和 30 天的安全性随访。安全性（主要）变量为治疗突发不良事件（TEAEs）发生率、因TEAEs而停药、失神或肌阵挛性癫痫发作发生率以及每28天失神或肌阵挛性癫痫发作天数的增加。疗效（次要）变量为每 28 天 GTCS 频率变化的百分比。Kaplan-Meier 估计保留率和按终生抗癫痫药物（ASM）数量进行的分析均为事后分析：总计有 239 名患者（平均年龄 = 27.9 岁，56.1% 为女性，18.4% 为儿童）入组并在该 OLE 中接受了≥1 次 LCM 治疗（中位治疗时间 = 3.2 年）；157 人（65.7%）完成了试验，82 人（34.3%）中止了试验。最常见的中止原因（≥10%）是撤销同意（30 [12.6%]）。据 Kaplan-Meier 估计，1、3 和 5 年的保留率分别为 87%、72% 和 60%。总体而言，222 名患者（92.9%）报告了 TEAEs；19 名患者（7.9%）因 TEAEs 而停药。失神或肌阵挛性发作天数或新的失神或肌阵挛性发作发生率增加的患者很少。与综合基线相比，每 28 天 GTCS 频率变化的中位百分比为-88.6%（范围 = -100.0 至 465.4，n = 238）。事后分析表明，终生有 1 次、2 次和≥3 次 ASM 的患者之间存在微小的数值差异：结果支持对 IGE 患者使用长期辅助 LCM 治疗 GTCS。长期辅助 LCM 具有良好的疗效和耐受性，与 LCM 开始前使用的 ASM 数量无关：临床试验注册：ClinicalTrials.gov：临床试验注册：ClinicalTrials.gov：NCT02408549。

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来源期刊

Epilepsia 医学-临床神经学

CiteScore

10.90

自引率

10.70%

发文量

319

审稿时长

2-4 weeks

期刊介绍： Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.