Toledo Manuel, Beale Rebecca, Evans Jennifer S, Steeves Sara, Elmoufti Sami, Townsend Rebecca, Whitesides John, Borghs Simon
Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
Costello Medical Consulting Ltd, Cambridge, UK.
Epilepsy Res. 2017 Dec;138:53-61. doi: 10.1016/j.eplepsyres.2017.10.008. Epub 2017 Oct 10.
Antiepileptic drug (AED) retention rates are frequently reported in the literature and used to inform clinical decision-making, but methodological differences in the determination of retention rates make comparisons between trials difficult. Open-label extension (OLE) studies of AEDs in patients with focal epilepsy were identified from the literature. Retention calculation methods were reviewed, and published AED retention rates qualitatively compared with corresponding data for brivaracetam (BRV), a synaptic vesicle protein 2A ligand. The search identified 40 publications (corresponding to 17 studies of nine AEDs: eslicarbazepine, gabapentin, lacosamide, levetiracetam, oxcarbazepine, perampanel, pregabalin, topiramate and zonisamide) meeting eligibility criteria for inclusion in the review. Three methodologies to estimate retention rate were identified, which differed in whether patients randomised to placebo in the preceding randomised controlled trials (RCTs) were included or analysed separately, and whether retention was measured from the start of the OLE or of active treatment exposure. The most robust, conservative approach included all patients and measured retention from start of active treatment exposure, whether during the blinded RCT or at the start of the OLE (placebo RCT patients). Data using this method was available for five AEDs in this review, including BRV. The corresponding BRV 52week retention rate (modal doses 50-200mg/day; therapeutic range) was 69.8% (63.3-66.7% for other AEDs at this time point). No statistical indirect comparison was performed, as study populations were clinically heterogeneous. To avoid inconsistencies in methodologies, and allow comparison between AEDs when OLE data are the only long-term data available, retention rate analyses would benefit from the development of consistent reporting standards and guidelines.
抗癫痫药物（AED）留存率在文献中经常被报道，并用于指导临床决策，但留存率测定方法上的差异使得不同试验之间难以进行比较。从文献中检索出了关于局灶性癫痫患者使用AED的开放标签扩展（OLE）研究。回顾了留存率的计算方法，并将已发表的AED留存率与突触囊泡蛋白2A配体布瓦西坦（BRV）的相应数据进行了定性比较。检索共识别出40篇符合纳入本综述标准的出版物（对应9种AED的17项研究：埃司利卡西平、加巴喷丁、拉科酰胺、左乙拉西坦、奥卡西平、吡仑帕奈、普瑞巴林、托吡酯和唑尼沙胺）。确定了三种估计留存率的方法，这些方法的不同之处在于是否纳入或单独分析在前一项随机对照试验（RCT）中随机分配到安慰剂组的患者，以及留存率是从OLE开始时还是从积极治疗暴露开始时进行测量。最稳健、保守的方法是纳入所有患者，并从积极治疗暴露开始时测量留存率，无论这是在盲法RCT期间还是在OLE开始时（安慰剂RCT患者）。本综述中有5种AED可获得使用该方法的数据，包括BRV。相应的BRV 52周留存率（模态剂量50 - 200mg/天；治疗范围）为69.8%（此时其他AED在该时间点的留存率为63.3 - 66.7%）。由于研究人群在临床上具有异质性，未进行统计学间接比较。为避免方法上的不一致，并在OLE数据是唯一可用的长期数据时允许AED之间进行比较，留存率分析将受益于制定一致的报告标准和指南。
