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Abstract：
Selecting appropriate antiseizure medications (ASMs) for combination therapy in patients with drug-resistant epilepsy (DRE) is a complex task that requires an empirical approach, especially in patients receiving polytherapy. We aimed to analyze the effectiveness of various three-drug combinations in a group of patients with DRE under real-world conditions. This single-center, longitudinal observational study investigated patients with drug-resistant focal epilepsy who received three-drug regimens in the outpatient clinic of Tongji Hospital from September 2019 to December 2022. The effectiveness of each triple regimen was evaluated by the seizure-free rate and within-patient ratio of the seizure frequency (a seizure frequency ratio [SFR]<1 indicated superior efficacy). The independent t-test or Mann-Whitney U test was used for effectiveness analysis, and P values were adjusted by the Benjamini-Hochberg method for multiple comparisons. A total of 511 triple trials comprising 76 different regimens were conducted among 323 enrolled patients. Among these triple regimens, lamotrigine (LTG)/valproic acid (VPA)/topiramate (TPM) was the most frequently prescribed (29.4%, n = 95). At the last clinical visit, 14.9% (n = 48) of patients achieved seizure freedom after receiving triple therapy. LTG/VPA/TPM and LTG/VPA/levetiracetam (LEV) exhibited the highest seizure-free rates at 17.9% and 12.8%, respectively. These two regimens also had significantly lower median SFRs of 0.48 (interquartile range [IQR], 0.17-0.85; adjusted P < 0.001) and 0.63 (IQR, 0.21-1.04; adjusted P < 0.01), respectively. LTG/VPA/perampanel (PER) was another promising regimen that showed marginal effectiveness (median SFR = 0.67; adjusted P = 0.053). LTG/VPA/phenobarbital had the highest incidence of regimen-specific side effects (40.0%, 4/10), while the incidence of side effects from LTG/VPA/LEV was minimal (5.1%, 2/39). In conclusion, LTG/VPA/TPM and LTG/VPA/LEV exhibited superior efficacy and good tolerability in treating patients with DRE. Our results provide preliminary insights into the selection of ASMs for three-drug combination therapies in this clinically challenging population.
摘要：
选择合适的抗癫痫药物（ASM）用于耐药癫痫（DRE）患者的联合治疗是一项复杂的任务，需要经验方法。尤其是在接受综合疗法的患者中。我们旨在分析真实世界条件下一组DRE患者中各种三种药物组合的有效性。这个单一中心，纵向观察性研究调查了2019年9月至2022年12月在同济医院门诊接受三药治疗的耐药局灶性癫痫患者.通过无癫痫发作率和癫痫发作频率的患者内比率来评估每种三联方案的有效性（癫痫发作频率比[SFR]<1表明疗效优异）。有效性分析采用独立t检验或曼-惠特尼U检验，通过Benjamini-Hochberg方法调整P值进行多重比较。共有511个三联试验，包括76个不同的方案，在323名入选患者中进行。在这些三联疗法中，拉莫三嗪（LTG）/丙戊酸（VPA）/托吡酯（TPM）是最常见的处方（29.4％，n=95）。在上次临床就诊时，14.9%(n=48)的患者在接受三联疗法后实现了癫痫发作自由。LTG/VPA/TPM和LTG/VPA/左乙拉西坦（LEV）的无癫痫发作率最高，分别为17.9%和12.8%。分别。这两种方案的SFR中位数也显着较低，为0.48（四分位距[IQR]，0.17-0.85；调整后P<0.001)和0.63(IQR，0.21-1.04；调整后P<0.01)，分别。LTG/VPA/perampanel（PER）是另一种有希望的方案，显示出边际疗效（中位数SFR=0.67；调整后P=0.053）。LTG/VPA/苯巴比妥的方案特异性副作用发生率最高(40.0%,4/10),而LTG/VPA/LEV的副作用发生率最低(5.1%，2/39).总之,LTG/VPA/TPM和LTG/VPA/LEV在治疗DRE患者中表现出优异的疗效和良好的耐受性。我们的结果为在这个具有临床挑战性的人群中选择三药联合疗法的ASM提供了初步见解。
