目的:报告来自两个双盲患者的辅助西诺膦酸盐和伴随的抗癫痫药物(ASM)对体重的影响,安慰剂对照,第二阶段研究(YKP3089C013[C013]和YKP3089C017[C017])及其开放标签扩展(OLE),从长期来看,开放标签阶段3安全性研究,YKP3089C021(C021)。
背景:Cenobamate是美国和欧盟批准用于治疗成人局灶性癫痫发作的ASM。一些ASM与体重增加相关(例如,丙戊酸盐,加巴喷丁,普瑞巴林),这会对患者健康产生负面影响。
方法:在每项研究中纳入不受控制的局灶性癫痫发作患者,服用稳定剂量的1-3种ASM。在C013中,将西诺膦酸滴定至200mg/天的目标剂量(最大OLE剂量400mg/天)。在C017中,患者被随机分配至西诺本100、200或400mg/天(最大OLE剂量400mg/天)。在C021中,锡溴酸铵被滴定至200mg/天的目标剂量(最大剂量400mg/天)。事后分析了距基线1年和2年时的中位体重变化。
结果:分析包括来自C013、C017(联合剂量组)的39、206和1054名患者,和C021,分别。从基线开始的平均体重变化范围为1年-0.2至-0.9kg,2年-1.0至+1.0kg。在停用丙戊酸钠1(-13.0kg,C013,n=1)或2年(-24.5千克,C017,n=2)和停用加巴喷丁1(-7.1kg,C017,n=2)或2年(-7.0千克,C017,n=2)。否则,同时接受丙戊酸钠的患者的中位体重相对于基线的变化,加巴喷丁,1年或普瑞巴林的范围为-3.1至2.6kg,2年为-1.6至2.7kg。
结论:在接受1年和2年治疗的患者中,辅助性cenobamate与体重相对于基线的临床显着变化无关。包括那些同时接受丙戊酸盐的人,加巴喷丁,或者普瑞巴林.
BACKGROUND: Clinical trials have shown that cenobamate (CNB) is an efficacious and safe anti-seizure medication (ASM) for drug-resistant focal epilepsy. Here, we analyzed one of the largest real-world cohorts, covering the entire spectrum of epilepsy syndromes, the efficacy and safety of CNB, and resulting changes in concomitant ASMs.
METHODS: We conducted a retrospective observational study investigating CNB usage in two German tertiary referral centers between October 2020 and June 2023 with follow-up data up to 27 months of treatment. Our primary outcome was treatment response. Secondary outcomes comprised drug response after 12 and 18 months, seizure freedom rates, CNB dosage and retention, adverse drug reactions (ADRs), and changes in concomitant ASMs.
RESULTS: 116 patients received CNB for at least two weeks. At 6 months, 98 patients were eligible for evaluation. Thereof 50% (49/98) were responders with no relevant change at 12 and 18 months. Seizure freedom was achieved in 18.4% (18/98) at 6 months, 16.7% (11/66), and 3.0% (1/33) at 12 and 18 months. The number of previous ASMs did not affect the seizure response rate. Overall, CNB was well-tolerated, however, in 7.7% (9/116), ADRs led to treatment discontinuation. The most frequent changes of concomitant ASMs included the discontinuation or reduction of sodium channel inhibitors, clobazam reduction, and perampanel discontinuation, while brivaracetam doses were usually left unchanged.
CONCLUSIONS: CNB proved to be a highly effective and generally well-tolerated ASM in patients with severe drug-resistant epilepsy, comprising a broad array of epilepsy syndromes beyond focal epilepsy.