Bootsma H P R, Ricker L, Diepman L, Gehring J, Hulsman J, Lambrechts D, Leenen L, Majoie M, Schellekens A, de Krom M, Aldenkamp A P
Department of Neurology, Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands.
Seizure. 2008 Jan;17(1):19-26. doi: 10.1016/j.seizure.2007.05.019. Epub 2007 Jul 6.
Two of the most commonly prescribed new antiepileptic drugs as add-on therapy for patients with chronic refractory epilepsies are topiramate and levetiracetam. In regulatory trials, both drugs were characterized as very promising new antiepileptic drugs. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice, also because head-to-head comparisons are lacking. Therefore, results from long-term open label observational studies that compare two or more new AEDs are crucial to determine the long-term performance of competing new antiepileptic drugs in clinical practice.
We analyzed all patients referred to a tertiary epilepsy centre who had been treated with topiramate from the introduction of the drug in spring 1993 up to a final assessment point mid-2002 and all patients who had been treated with LEV in the same centre from the introduction of the drug in early 2001 up to a final assessment point end-2003 using a medical information system.
Three hundred and one patients were included for levetiracetam and 429 patients for TPM. Retention rate after 1 year was 65.6% for LEV-treated patients and 51.7% for TPM-treated patients (p=0.0015). Similarly, retention rates for LEV were higher at the 24-month mark: 45.8% of LEV-treated patients and 38.3% of TPM-treated patients were still continuing treatment (p=0.0046). Adverse events led to drug discontinuation in 21.9% of TPM-treated patients compared to 6.0% of LEV-treated patients (p<0.001). The number of patients discontinuing treatment because of lack of efficacy was similar for both groups. Seizure freedom rates varied between 11.6 and 20.0% for TPM and between 11.1 and 14.3% for LEV per 6-months interval. Several important AED specific adverse events leading to drug discontinuation were identified, including neurocognitive side effects from TPM and mood disorders from LEV.
The retention rate for LEV is significantly higher than for TPM. LEV had a more favourable side effect profile than TPM with comparable efficacy. Patients on TPM discontinued treatment mainly because of neurocognitive side effects. In the treatment with LEV, the effects on mood must not be underestimated.
作为慢性难治性癫痫患者的附加治疗药物，托吡酯和左乙拉西坦是两种最常被处方的新型抗癫痫药物。在监管试验中，这两种药物均被视为非常有前景的新型抗癫痫药物。然而，这些高度受控的短期临床试验结果不能简单地外推至日常临床实践，部分原因还在于缺乏直接对比。因此，比较两种或更多新型抗癫痫药物的长期开放标签观察性研究结果对于确定竞争性新型抗癫痫药物在临床实践中的长期表现至关重要。
我们分析了自1993年春季该药引入至2002年年中最终评估点期间，在一家三级癫痫中心接受托吡酯治疗的所有患者，以及自2001年初该药引入至2003年底最终评估点期间，在同一中心接受左乙拉西坦治疗的所有患者，使用了一个医学信息系统。
纳入左乙拉西坦治疗的患者有301例，纳入托吡酯治疗的患者有429例。左乙拉西坦治疗组患者1年后的留存率为65.6%，托吡酯治疗组患者为51.7%（p = 0.0015）。同样，在24个月时左乙拉西坦的留存率更高：左乙拉西坦治疗组45.8%的患者和托吡酯治疗组38.3%的患者仍在继续治疗（p = 0.0046）。不良事件导致托吡酯治疗组21.9%的患者停药，而左乙拉西坦治疗组为6.0%（p < 0.001）。两组因疗效不佳而停药的患者数量相似。每6个月的无癫痫发作率在托吡酯组为11.6%至20.0%，在左乙拉西坦组为11.1%至14.3%。确定了几种导致停药的重要的抗癫痫药物特异性不良事件类型，包括托吡酯引起的神经认知副作用和左乙拉西坦引起的情绪障碍。
左乙拉西坦的留存率显著高于托吡酯。左乙拉西坦的副作用谱比托吡酯更有利，疗效相当。托吡酯治疗的患者停药主要是因为神经认知副作用。在左乙拉西坦治疗中，对情绪的影响不可低估。
