艾司利卡西平治疗成人新发局灶性癫痫的长期疗效和安全性：一项开放性扩展研究。

Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study.

机构信息

Department of Neurology, Centre for Cognitive Neuroscience, Christian-Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.

Institute of Public Health, Medical Decision-Making, and Health Technology Assessment, Private University for Health Sciences, Medical Informatics, and Technology, Hall in Tyrol, Austria.

出版信息

Epilepsia. 2020 Oct;61(10):2129-2141. doi: 10.1111/epi.16666. Epub 2020 Sep 17.

DOI:10.1111/epi.16666

PMID:32944934

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7693183/

Abstract

OBJECTIVE

To assess the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) monotherapy during long-term treatment.

METHODS

An open-label extension (OLE) study was conducted in adults completing a phase 3, randomized, double-blind, noninferiority trial, during which they had received monotherapy with either once-daily ESL or twice-daily controlled-release carbamazepine (CBZ-CR) for newly diagnosed focal epilepsy. In the OLE study, all patients received ESL (800-1600 mg/d) for 2 years. Primary efficacy outcome was retention time (from baseline of the OLE study). Secondary efficacy assessments included seizure freedom rate (no seizures during the OLE study) and responder rate (≥50% seizure frequency reduction from baseline of double-blind trial). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs).

RESULTS

Of 206 randomized patients, 96 who received ESL in the double-blind trial (ESL/ESL) and 88 who received CBZ-CR in the double-blind trial (CBZ-CR/ESL) were treated with ESL monotherapy (89.3% overall). Treatment retention time was similar between groups, with low probability of ESL withdrawal overall (<0.07 at any time). After 24 months, the probability of ESL withdrawal was 0.0638 (95% confidence interval [CI] = 0.0292-0.1366) in the ESL/ESL group and 0.0472 (95% CI = 0.0180-0.1210) in the CBZ-CR/ESL group. Seizure freedom rates were 90.6% (ESL/ESL) and 80.7% (CBZ-CR/ESL; P = .0531). Responder rates remained >80% in both groups throughout the study. Incidence of serious TEAEs was similar between groups (7.3% vs 5.7%; 0% vs 1.1% possibly related), as were the incidences of TEAEs considered at least possibly related to treatment (17.7% vs 18.2%) and TEAEs leading to discontinuation (3.1% vs 4.5%). The types of TEAEs were generally consistent with the known safety profile of ESL.

SIGNIFICANCE

ESL monotherapy was efficacious and generally well tolerated over the long term, including in patients who transitioned from CBZ-CR monotherapy. No new safety concerns emerged.

摘要

目的

评估醋酸艾司利卡西平（ESL）单药治疗的长期疗效、安全性和耐受性。

方法

在一项完成的 3 期、随机、双盲、非劣效性试验的成年患者中开展了一项开放标签扩展（OLE）研究，他们在该试验中接受了每日一次 ESL 或每日两次控释卡马西平（CBZ-CR）单药治疗，用于新发局灶性癫痫。在 OLE 研究中，所有患者均接受 ESL（800-1600mg/d）治疗 2 年。主要疗效结局为保留时间（从 OLE 研究的基线开始）。次要疗效评估包括无癫痫发作率（OLE 研究期间无癫痫发作）和应答率（双盲试验基线时癫痫发作频率降低≥50%）。安全性评估包括治疗后出现的不良事件（TEAE）的评估。

结果

在 206 名随机患者中，96 名在双盲试验中接受 ESL（ESL/ESL）治疗，88 名在双盲试验中接受 CBZ-CR 治疗（CBZ-CR/ESL），随后接受 ESL 单药治疗（总体为 89.3%）。两组的治疗保留时间相似，总体 ESL 停药的可能性较低（任何时间均＜0.07）。在 24 个月时，ESL/ESL 组 ESL 停药的概率为 0.0638（95%置信区间[CI] = 0.0292-0.1366），CBZ-CR/ESL 组为 0.0472（95% CI = 0.0180-0.1210）。无癫痫发作率分别为 90.6%（ESL/ESL）和 80.7%（CBZ-CR/ESL；P=0.0531）。在整个研究过程中，两组的应答率均保持在＞80%。两组严重不良事件（TEAE）的发生率相似（7.3%比 5.7%；0%比 1.1%可能相关），至少可能与治疗相关的 TEAE（17.7%比 18.2%）和导致停药的 TEAE（3.1%比 4.5%）发生率也相似。TEAE 的类型通常与 ESL 的已知安全性特征一致。