WA Adult Epilepsy Service, Perth, WA, Australia.
Central Clinical School, Monash University, Melbourne, Vic., Australia.
Epilepsia. 2021 Jan;62(1):228-237. doi: 10.1111/epi.16765. Epub 2020 Nov 25.
Randomized studies in drug-resistant epilepsy (DRE) typically involve addition of a new anti-seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach.
Longitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time-to-event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution.
A total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow-up was 3.2 years. Substitution was more likely if the new ASM was enzyme-inducing or in patients with a greater number of concurrent ASMs. ASM add-on was more likely if a γ-aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add-on and substitution groups. No difference between the add-on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months.
Adding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics.
耐药性癫痫（DRE）的随机研究通常涉及添加新的抗癫痫药物（ASM）。然而，在临床实践中，如果患者已经服用多种 ASM，则通常会替换当前的一种 ASM，尽管很少有证据支持这种方法。
对 DRE 患者开始使用以前未尝试过的 ASM 后的癫痫发作结果进行纵向前瞻性研究。使用多变量时间事件和逻辑回归模型来评估新 ASM 通过添加或替换引入时的结果。
在 2010 年至 2018 年间，共分析了 436 例 DRE 成年患者的 816 次 ASM 变化。新 ASM 添加了 407 次（50.1%），替换了 409 次（49.9%）。平均患者随访时间为 3.2 年。如果新 ASM 是酶诱导剂或同时服用的 ASM 数量较多，则更有可能进行替换。如果引入 γ-氨基丁酸（GABA）激动剂或患者之前尝试过更多的 ASM，则更有可能添加 ASM。由于不耐受而停药的发生率在添加组和替换组之间相似。在 12 个月时≥50%癫痫发作减少的主要结局方面，添加和替换 ASM 引入策略之间没有差异。
在 DRE 中添加或替换新的 ASM 对癫痫发作结果的影响相同。这些发现证实，DRE 中的 ASM 改变可以根据同时进行的 ASM 治疗和患者特征进行个体化。
