首次抗癫痫药物治疗失败后的治疗方案反应。
Response to treatment schedules after the first antiepileptic drug failed.
机构信息
Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
出版信息
Epilepsia. 2018 Nov;59(11):2118-2124. doi: 10.1111/epi.14565. Epub 2018 Sep 24.
OBJECTIVE
After the failure of the first antiepileptic drug (AED) at doses > 50% defined daily dose (DDD), there are three options for patients with epilepsy: combination therapy, alternative therapy, and increased dosage of the first AED. However, present studies have not provided evidence for which option is best. Therefore, we conducted this retrospective observational cohort study to compare the effects of three treatment schedules.
METHODS
Patients diagnosed with newly diagnosed epilepsy at the epilepsy clinic of West China Hospital between August 2006 and February 2016 were evaluated for eligibility for this study. Patients who failed to respond to the first AED at doses > 50% DDD were included, and divided into three cohorts: increased dosage, combination therapy, and alternative therapy. Cumulative incidence curves for time to seizure freedom were compared for different cohorts by Gray test. Competing risk regression was conducted to evaluate the association of clinical predictors with seizure freedom.
RESULTS
Altogether, 502 patients (277 male, 55.2%) were included for further analysis, and the median duration of follow-up was 32 months (range = 8-127). The probability of seizure freedom was significantly higher in patients receiving combination therapy (n = 323) compared to the alternative therapy cohort (n = 76, P < 0.001) and increased dosage cohort (n = 103, P = 0.025). Competing risk regression analysis showed that combination therapy significantly increased the probability of seizure freedom (hazard ratio [HR] = 2.423, 95% confidence interval [CI] = 1.529-3.841, P < 0.001). In addition, male sex and generalized seizure were significantly associated with increased probability of seizure freedom (male sex: HR = 1.440, 95% CI = 1.106-1.880, P = 0.007; generalized seizure: HR = 1.543, 95% CI = 1.176-2.020, P = 0.002).
SIGNIFICANCE
Combination therapy may increase the probability of seizure freedom for patients with first AED failure due to lack of efficacy.
目的
在首次抗癫痫药物（AED）剂量> 50% 定义日剂量（DDD）失败后，癫痫患者有三种选择：联合治疗、替代治疗和增加首剂 AED 的剂量。然而，目前的研究并未提供哪种选择最好的证据。因此，我们进行了这项回顾性观察性队列研究，以比较三种治疗方案的效果。
方法
本研究评估了 2006 年 8 月至 2016 年 2 月在华西医院癫痫诊所新诊断为癫痫的患者是否符合入组条件。纳入对首剂 AED 剂量> 50% DDD 反应不佳的患者，并将其分为三组：增加剂量、联合治疗和替代治疗。通过 Gray 检验比较不同队列的无癫痫发作时间累积发生率曲线。采用竞争风险回归评估临床预测因素与无癫痫发作的相关性。
结果
共纳入 502 例患者（男 277 例，55.2%）进行进一步分析，中位随访时间为 32 个月（范围 8-127 个月）。与替代治疗组（n=76，P<0.001）和增加剂量组（n=103，P=0.025）相比，接受联合治疗（n=323）的患者无癫痫发作的概率显著更高。竞争风险回归分析显示，联合治疗显著增加了无癫痫发作的概率（风险比[HR] = 2.423，95%置信区间[CI] = 1.529-3.841，P<0.001）。此外，男性和全身性发作与无癫痫发作的概率增加显著相关（男性：HR=1.440，95%CI=1.106-1.880，P=0.007；全身性发作：HR=1.543，95%CI=1.176-2.020，P=0.002）。
意义
对于因疗效不佳而首次 AED 治疗失败的患者，联合治疗可能会增加无癫痫发作的概率。
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