Ohtsuka Yoko, Yoshinaga Harumi, Shirasaka Yukiyoshi, Takayama Rumiko, Takano Hiroki, Iyoda Kuniaki
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Epilepsy Res. 2014 Nov;108(9):1627-36. doi: 10.1016/j.eplepsyres.2014.08.019. Epub 2014 Sep 2.
To evaluate the efficacy, safety, and pharmacokinetics of rufinamide as an adjunctive therapy for patients with Lennox-Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial.
We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to rufinamide or placebo. The primary efficacy variable was the percent change in the tonic-atonic seizure frequency per 28 days.
Of the 59 patients, 29 were randomized to the rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the rufinamide group than in the placebo group; the median percent change in frequency of tonic-atonic seizures was -24.2% and -3.3%, respectively, (p=0.003) and that of total seizures was -32.9% and -3.1%, respectively (p<0.001). Subgroup analyses indicated that the efficacy of rufinamide was consistent independent of clinical background characteristics. The common treatment-related adverse events in the rufinamide group were decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%). Transient seizure aggravations were observed in 13 (22.0%) of the 59 patients, though a causal relationship with rufinamide was suspected in only one patient. All adverse events were mild to moderate in severity. The mean plasma concentration of rufinamide between 1 and 9 within 12h after administration was 17.2 μg/mL.
The present results showed a favorable risk-benefit profile for rufinamide as an adjunctive therapy for patients with LGS.
在一项随机、双盲、安慰剂对照试验中，评估鲁非酰胺作为辅助治疗药物用于伦诺克斯 - 加斯托综合征（LGS）患者的疗效、安全性和药代动力学。
我们开展了一项多中心临床试验，包括为期4周的基线期、2周的滴定期、10周的维持期，以及一次随访或进入开放标签扩展期。招募年龄在4至30岁、正在服用1至3种抗癫痫药物的LGS患者。在基线期之后，患者被随机分配至鲁非酰胺组或安慰剂组。主要疗效变量是每28天强直 - 失张力发作频率的变化百分比。
59例患者中，29例被随机分配至鲁非酰胺组，30例被分配至安慰剂组。鲁非酰胺组癫痫发作频率显著低于安慰剂组；强直 - 失张力发作频率的中位数变化百分比分别为 -24.2% 和 -3.3%（p = 0.003），总发作频率的中位数变化百分比分别为 -32.9% 和 -3.1%（p < 0.001）。亚组分析表明，鲁非酰胺的疗效不受临床背景特征影响，具有一致性。鲁非酰胺组常见的治疗相关不良事件包括食欲减退（17.2%）、嗜睡（17.2%）和呕吐（13.8%）。59例患者中有13例（22.0%）观察到短暂的癫痫发作加重，不过仅1例患者怀疑与鲁非酰胺存在因果关系。所有不良事件的严重程度均为轻度至中度。给药后12小时内1至9小时的鲁非酰胺平均血浆浓度为17.2μg/mL。
目前的结果表明，鲁非酰胺作为LGS患者的辅助治疗药物，具有良好的风险效益比。
