拉考沙胺添加治疗中国部分性癫■发作患者的疗效和安全性:一项随机双盲试验和开放标签扩展试验的亚组分析和事后分析

目的评估抗癫■药拉考沙胺添加治疗对控制不佳的部分性癫■发作成年患者的疗效和安全性。方法EP0008(NCT01710657)是一项为期24周在中国和日本16~70岁控制不佳的部分性癫■发作患者中开展的随机、双盲、安慰剂对照临床试验。在双盲试验中完成维持期的患者可进入开放标签扩展性试验EP0009(NCT01832038)。本研究针对两项试验中的中国536例部分性癫■发作患者进行分析,经剔除筛选失败的130例患者,共计406例中国部分性癫■发作患者入组,随机分为安慰剂组(136例)、拉考沙胺200 mg·d^-1组(136例)和拉考沙胺400 mg·d^-1组(134例)。结果406例中358例(88.2%)完成试验。从基线期至维持期,拉考沙胺400 mg·d^-1组和拉考沙胺200 mg·d^-1组每28 d癫■发作频次分别减少43.1%和33.6%,与安慰剂组比较,差异有显著统计学意义(P<0.001)。拉考沙胺400 mg·d^-1组、拉考沙胺200 mg·d^-1组、安慰剂组治疗期间发生率>10%的不良事件为头晕(分别为33.8%、14.7%、11.0%)和鼻咽炎(分别为11.3%、10.3%、8.8%)。同时联合使用钠离子通道阻滞剂(SCBs)患者的头晕发生率高于联合使用非SCBs患者。拉考沙胺联合使用SCBs时,滴定期患者的头晕发生率高于维持期。开放标签试验加量策略灵活,头晕发生率降低,患者的耐受性提高。结论拉考沙胺(200和400 mg·d^-1)用于中国控制不佳的部分性癫■发作患者有效,耐受性良好。

Hypersensitive syndrome reaction of antiepileptic drug: two case reports and literature review

Hypersensitivity syndrome reaction of antiepileptic drug （AED） can induce serious cutaneous, hematological and hepatic events. In severe cases, fulminant hepatic failure may necessitate liver transplantation, and most patients die due to the liver failure. Severe adverse cutaneous reactions, including Steven-Johnson syndrome （SJS）, toxic epidermal necrolysis （TEN） and hypersensitivity syndrome, are rare but life-threatening. Its morality rate is as high as 5%-50%. Accurate early diagnosis and timely treatment may contribute to decreased morality rate. In this paper, we reported cases of hypersensitive syndrome reaction to carbamazepine （CBZ） or phenobarbital （PB） in two patients with epilepsy. Clarification of the therapeutic process and the early manifestation of epilepsy may be helpful to improve the epilepsy therapy while avoiding the potential severe adverse cutaneous reactions of AED. The two reported cases highlighted that the therapeutic process of CBZ and PB might lead to the fatal allergic reaction, which was mainly caused by the absence of epoxide-hydroxylase and the defect of hepatocytes.