目的:Perampanel(PER)和Lacosamide(LCM)是新的第三代抗癫痫药物(ASM),已被批准用于中国四岁以上儿童局灶性癫痫的单一治疗。2021年。很少有研究分析PER单一疗法在4岁以上儿科患者中的应用,没有研究比较PER单药治疗与LCM单药治疗在局灶性癫痫患儿中的疗效和耐受性。本研究旨在调查疗效,耐受性,以及PER和LCM单药治疗对新诊断局灶性癫痫患儿行为和情绪的影响,这有利于临床医生有更多的选择来治疗小儿局灶性癫痫。
方法:这是一个前瞻性的,单中心,观察性研究涉及新诊断的局灶性癫痫患儿(发病年龄≥4岁),接受PER或LCM作为主要单药治疗。结果包括保留,作为响应者,以及3、6和12个月后的无癫痫发作率。在整个随访期间发现不良事件(AE)。在基线以及三个月和六个月后,使用Achenbach儿童行为清单(CBCL/4-16)评估行为结果。
结果:使用随机化,60名接受PER的患者(31名女性,29名男性,中位年龄:7.79[5.34,10.16]岁,中位剂量:3.0[2.0,4.0]mg/天)和60名接受LCM的患者(25名女性,35名男性,中位年龄:7.72[5.91,10.72]岁,中位剂量:150.0[100.0,200.0]mg/天)纳入研究。在12个月的随访中,PER和LCM组中的保留率,都是90.4%,应答率分别为65.4%和71.2%,而无癫痫发作率分别为57.7%和67.3%,分别。保留率没有显着差异,两组患者的反应率和无癫痫发生率比较(P>0.05)。BECTS患者的应答率没有显着差异,异常脑磁共振成像(MRI),两组癫痫发作类型比较(P>0.05)。在PER组中,28.8%(15/52)的患者出现不良事件,其中最常报告的是易怒(n=7;13.5%),头晕(n=5;9.6%),嗜睡(n=3;5.8%),共济失调(n=1;1.9%),头痛(n=1;1.9%),和皮疹(n=1;1.9%)。在LCM组中,15.4%(8/52)的患者出现不良事件,包括头痛(n=4;7.5%),头晕(n=4;7.5%),恶心(n=2;3.8%),嗜睡(n=2;3.8%),烦躁(n=1;1.9%),胃痛(n=1;1.9%),呕吐(n=1;1.9%)。PER组的烦躁发生率明显高于LCM组(13.5%vs.1.9%,P=0.031),主要发生在给药后8周内。通过父母在生活中的观察评估,易怒的患者对周围的人没有危险。症状在几个月内自发缓解。总分的结果,内化分数,在基线和3个月和6个月之间,在PER和LCM组中,CBCL的外部化评分未显示出统计学上的显著差异.接受PER和LCM单药治疗的患者的行为和情绪特征没有实质性变化。
结论:本研究记录了PER和LCM与新诊断的局灶性癫痫患儿的单一治疗相似的良好疗效和良好耐受性,并且没有行为或情绪影响。根据CBCL的评估。尽管在药物开始后不久,PER单药治疗的烦躁发生率可能高于LCM单药治疗。这种副作用似乎在几个月内自发消退。目前,这项研究是关于PER和LCM单药治疗小儿新诊断局灶性癫痫疗效评估的第一个研究,耐受性,以及在中国的行为。
Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in
China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy.
This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4-16) at baseline and after three and six months.
Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy.
The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in
China.