在第一种抗癫痫药物治疗失败后，应采用替代单药治疗还是联合治疗？一项 30 年队列研究的观察结果。

Should substitution monotherapy or combination therapy be used after failure of the first antiseizure medication? Observations from a 30-year cohort study.

机构信息

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.

出版信息

Epilepsia. 2023 May;64(5):1248-1258. doi: 10.1111/epi.17573. Epub 2023 Mar 21.

DOI:10.1111/epi.17573

PMID:36869855

Abstract

OBJECTIVES

To assess the temporal trends in the use of second antiseizure (ASM) regimens and compare the efficacy of substitution monotherapy and combination therapy after failure of initial monotherapy in people with epilepsy.

METHODS

This was a longitudinal observational cohort study conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. We included patients who were newly treated for epilepsy with ASMs between July 1982, and October 2012. All patients were followed up for a minimum of 2 years. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow up.

RESULTS

During the study period, 498 patients were treated with a second ASM regimen after failure of the initial ASM monotherapy, of whom 346 (69%) were prescribed combination therapy and 152 (31%) were given substitution monotherapy. The proportion of patients receiving second regimen as combination therapy increased during the study period from 46% in first epoch (1985-1994) to 78% in the last (2005-2015) (RR = 1.66, 95% CI: 1.17-2.36, corrected-p = .010). Overall, 21% (104/498) of the patients achieved seizure freedom on the second ASM regimen, which was less than half of the seizure-free rate on the initial ASM monotherapy (45%, p < .001). Patients who received substitution monotherapy had similar seizure-free rate compared with those who received combination therapy (RR = 1.17, 95% CI: 0.81-1.69, p = .41). Individual ASMs used, either alone or in combination, had similar efficacy. However, the subgroup analysis was limited by small sample sizes.

SIGNIFICANCE

The choice of second regimen used based on clinical judgment was not associated with treatment outcome in patients whose initial monotherapy failed due to poor seizure control. Alternative approaches such as machine learning should be explored to aid individualized selection of the second ASM regimen.

摘要

目的

评估第二抗癫痫药物（ASM）方案使用的时间趋势，并比较初始单药治疗失败后替代单药治疗与联合治疗的疗效。

方法

这是一项在苏格兰格拉斯哥西部医务室癫痫科进行的纵向观察性队列研究。我们纳入了 1982 年 7 月至 2012 年 10 月期间新接受 ASM 治疗的癫痫患者。所有患者的随访时间均至少为 2 年。无发作定义为末次随访时未服用任何药物且无发作至少 1 年。

结果

在研究期间，498 例初始 ASM 单药治疗失败后接受了第二种 ASM 方案治疗，其中 346 例（69%）接受了联合治疗，152 例（31%）接受了替代单药治疗。在研究期间，接受第二种方案作为联合治疗的患者比例从第一时期（1985-1994 年）的 46%增加到最后一个时期（2005-2015 年）的 78%（RR=1.66，95%CI：1.17-2.36，校正后 p=0.010）。总体而言，498 例患者中有 21%（104/498）在第二种 ASM 方案中实现了无发作，低于初始 ASM 单药治疗的无发作率（45%，p<0.001）。接受替代单药治疗的患者与接受联合治疗的患者无发作率相似（RR=1.17，95%CI：0.81-1.69，p=0.41）。单独使用或联合使用的各种 ASM 药物具有相似的疗效。然而，亚组分析受到样本量较小的限制。