Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Republic of Korea.
Seizure. 2013 Apr;22(3):185-8. doi: 10.1016/j.seizure.2012.12.002. Epub 2012 Dec 30.
The efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures.
We enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period.
A total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P=0.054). Based on Kaplan-Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months.
This study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.
抗惊厥药物左乙拉西坦（LEV）的疗效和安全性已得到充分证实，但很少有临床研究调查对 LEV 的耐受性。本研究旨在评估成人耐药性部分发作性癫痫患者对 LEV 初始疗效的丧失。
我们招募了开始接受附加 LEV 治疗的耐药性部分性癫痫患者。每三个月评估一次 LEV 的疗效，根据每月平均癫痫发作次数来决定癫痫发作频率。 responder 定义为癫痫发作频率较基线降低≥50%的患者。无癫痫发作定义为从 LEV 治疗开始到评估期无癫痫发作状态。初始疗效丧失定义为在 LEV 治疗的前三个月内从 responder 状态转变为非 responder 状态。
共分析了 95 例癫痫患者。在 LEV 治疗的前三个月中，95 例患者中有 50 例（52.6%）的癫痫发作减少≥50%。有 9 例（18.0%）患者在第二三个月期间出现初始疗效丧失。相比之下，在最初的三个月内无应答者中只有两例（4.0%）在接下来的三个月内成为应答者。然而，这一差异没有达到统计学意义（P=0.054）。基于 Kaplan-Meier 生存估计，在最初的三个月内对 LEV 治疗有反应的患者中，有 49.2%预计在 42 个月时会失去这种反应。LEV 治疗初始疗效丧失大多发生在 18 个月内。
本研究表明，尽管需要进行更大的前瞻性研究来证实这一观察结果，但耐受性的发生比治疗后期疗效的增加更为常见。
