Kothare Sanjeev, Kluger Gerhard, Sachdeo Rajesh, Williams Betsy, Olhaye Omar, Perdomo Carlos, Bibbiani Francesco
Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Medical Center, 223 East 34th Street, New York, NY 10016, USA.
Neuropaediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Centre for Children and Adolescents, Schoen Klinik Vogtareuth Krankenhausstrasse, 20 D-83569 Vogtareuth, Germany; Paracelsus Medical University Salzburg, Salzburg, Austria.
Seizure. 2017 Apr;47:25-33. doi: 10.1016/j.seizure.2017.02.008. Epub 2017 Feb 17.
Lennox-Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, rufinamide dosing and titration may differ from the trial setting. Here, rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies.
Rufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared.
Results demonstrated that a rapid titration schedule (7 or 14 days) of rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic-atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study - somnolence, vomiting, and pyrexia - occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings.
A lower dose and slower titration schedule ("low and slow") may reduce incidence of AEs without compromising efficacy of rufinamide in LGS.
Lennox-Gastaut综合征（LGS）是一种罕见的、严重的儿童期起病的癫痫，难以控制。卢非酰胺适用于辅助治疗成人及≥1岁儿科患者中与LGS相关的癫痫发作。在临床实践中，卢非酰胺的给药和滴定可能与试验环境有所不同。在此，将卢非酰胺的临床试验数据与实际临床经验进行比较，以深入了解最佳给药和滴定策略。
回顾卢非酰胺III期和开放标签扩展（OLE）研究；分析滴定和剂量对不良事件（AE）及同时使用抗癫痫药物（AED）的影响。通过PubMed检索确定卢非酰胺在LGS中的实际临床研究。提取并比较临床数据。
结果表明，卢非酰胺快速滴定方案（7天或14天）对大多数患者是可耐受的，并导致全身强直 - 失张力发作总数显著减少，疗效和耐受性在3年中持续存在。III期研究中最常见的AE——嗜睡、呕吐和发热——发生在治疗的前3周，一小部分患者在这段时间内无法达到目标剂量。同时使用AED对卢非酰胺的血浆浓度无临床显著影响。实际临床研究的数据与III期和OLE研究结果一致。然而，相对于临床试验中使用的方案，实际临床中通常采用较低剂量和较慢的滴定方案。
较低剂量和较慢的滴定方案（“低剂量慢滴定”）可能会降低AE的发生率，而不影响卢非酰胺治疗LGS的疗效。
