Baulac M, Byrnes W, Williams P, Borghs S, Webster E, De Backer M, Dedeken P
Pitié-Salpêtrière Hospital, IHU-ICM, Paris, France.
UCB Pharma, Raleigh, NC, USA.
Acta Neurol Scand. 2017 Apr;135(4):434-441. doi: 10.1111/ane.12691. Epub 2016 Oct 6.
To assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB.
In this open-label trial, LCM was initiated at 100 mg/day and up-titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks' maintenance (21-week treatment period). The primary outcome was retention rate on LCM.
Due to recruitment challenges, fewer than the planned 300 patients participated in the trial, resulting in the trial being underpowered. Overall, 120 patients (mean age 39.7 years) started and 93 completed the trial. The most frequently used SCBs were lamotrigine (39.2%), carbamazepine (30.8%) and oxcarbazepine (27.5%). Eighty-four patients adhered to protocol and discontinued their SCB after cross-titration, but there was insufficient evidence for 36 patients. Retention rate was 73.3% (88/120) for all patients and 83.3% (70/84) for those with evidence of SCB discontinuation. Seizure freedom for patients completing maintenance was 14.0% (13/93). Discontinuation due to adverse events (6.7%) and lack of efficacy (3.3%) occurred primarily during cross-titration. Most frequently reported adverse events during treatment were dizziness (23.3%), headache (15.0%) and fatigue (8.3%).
In patients with uncontrolled seizures on LEV/SCB, the LCM/LEV combination appeared to be effective and well tolerated. A cross-titration schedule-flexible LCM up-titration, concomitant SCB down-titration and stable background LEV-could present a feasible and practical approach to initiating LCM while minimizing pharmacodynamic interactions with a SCB.
前瞻性评估在左乙拉西坦（LEV）和钠通道阻滞剂（SCB）联合治疗效果不佳的局灶性癫痫患者中，在逐渐减少SCB剂量的同时添加拉科酰胺（LCM）至LEV治疗方案中的有效性。
在这项开放标签试验中，LCM起始剂量为100mg/天，并在9周内逐渐增加至200 - 600mg/天；当LCM剂量达到200mg/天时开始逐渐减少SCB剂量。患者维持稳定的LCM/LEV剂量12周（治疗期共21周）。主要结局指标为LCM的留存率。
由于招募困难，参与试验的患者少于计划的300例，导致试验效能不足。总体而言，120例患者（平均年龄39.7岁）开始试验，93例完成试验。最常用的SCB为拉莫三嗪（39.2%）、卡马西平（30.8%）和奥卡西平（27.5%）。84例患者遵循方案并在交叉滴定后停用SCB，但36例患者缺乏充分证据。所有患者的留存率为73.3%（88/120），有证据表明停用SCB的患者留存率为83.3%（70/84）。完成维持治疗的患者无癫痫发作率为14.0%（13/93）。因不良事件停药（6.7%）和因缺乏疗效停药（3.3%）主要发生在交叉滴定期间。治疗期间最常报告的不良事件为头晕（23.3%）、头痛（15.0%）和疲劳（8.3%）。
在LEV/SCB治疗下癫痫发作未得到控制的患者中，LCM/LEV联合治疗似乎有效且耐受性良好。一种交叉滴定方案——灵活增加LCM剂量、同时逐渐减少SCB剂量以及维持稳定的背景LEV治疗——可能是启动LCM治疗的一种可行且实用的方法，同时可最大程度减少与SCB的药效学相互作用。
