Cenobamate上市后治疗局灶性癫痫的经验:一项多中心队列研究。

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
CNS drugs Pub Date : 2025-03-01 Epub Date: 2025-02-15 DOI:10.1007/s40263-025-01158-8
Adam Strzelczyk, Felix von Podewils, Hajo M Hamer, Susanne Knake, Felix Rosenow, Kerstin Alexandra Klotz, Gerhard Kurlemann, Nico Melzer, Elisa Buhleier, Catrin Mann, Laurent M Willems, Johann Philipp Zöllner, Bernadette Gaida, Jeanne Cuny, David Bellaire, Ilka Immisch, Leena Kämppi, Andreas Brunklaus, Susanne Schubert-Bast
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引用次数: 0

摘要

背景:在随机对照试验中,佐剂cenobamate (CNB)已被证明可降低耐药局灶性癫痫患者的癫痫发作频率。在现实环境中进行的研究提供了有价值的补充数据,以进一步表征该药物的特征。目的:评价佐剂CNB (adjuvant cenobamate, CNB)在局灶性癫痫临床治疗中的疗效、保留性和耐受性,并探讨可能预测这些结果的因素。方法:这项多中心、回顾性队列研究纳入了2020年10月至2023年4月期间在7个癫痫中心开始CNB治疗的所有患者。从患者病历中收集基线和随访数据,包括临床特征和结局数据,如癫痫发作频率、CNB剂量、医生评估的临床总体印象变化、治疗后出现的不良事件(teae)、CNB保留和停药原因。结果:共234例患者[平均年龄40.7±14岁,中位40岁,范围11 ~ 82岁;5名18岁以下的青少年;99例(42.3%)男性。研究入组时的平均癫痫持续时间为23.2±14.5年(中位21年,范围0.75-63年),癫痫发作的平均年龄为17.5±13.0岁(中位17年,范围0.1-71年)。患者在开始CNB前平均服用2.6±0.8(中位数3)次抗癫痫药物(asm),既往抗癫痫药物(asm)平均失败6±3.3(中位数6)次。CNB暴露时间从5天到1162天不等,总暴露时间为264.7年。3个月时保留率为92.6%,6个月时为87.2%,12个月时为77.8%。3个月时,52.6%的患者癫痫发作减少50%,14.5%的患者癫痫发作自由;到12个月时,47.7%的患者维持50%的有效率,11.9%的患者无癫痫发作。在性别、病因、发作部位、asm次数或靶剂量的基础上,没有观察到应答率的显著差异。平均最大CNB剂量为236.7±97.4 mg(中位200 mg,范围12.5-450 mg), 28例患者(12.0%)滴定至400 mg或以上。在CNB治疗期间,43.6%的患者能够停药,另外24.4%的患者能够减少伴随ASM的剂量。在CNB治疗期间,144例(61.5%)患者发生teae。最常见的teae是镇静(n = 84, 35.9%)、头晕(n = 58, 24.8%)和共济失调(n = 23, 9.8%)。结论:CNB具有较高的临床有用的50%应答率(47.7%)和1年总保留率(77.8%)。我们无法确定反应和保留的具体预测因素,这表明CNB可能对有多次失败的asm病史、大量并发asm和任何局灶性癫痫定位或病因的患者有益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Post-marketing Experience with Cenobamate in the Treatment of Focal Epilepsies: A Multicentre Cohort Study.

Background: In randomised controlled trials, adjunctive cenobamate (CNB) has been shown to reduce seizure frequency in patients with drug-resistant focal epilepsy. Studies conducted in real-world settings provide valuable complementary data to further characterise the drug's profile.

Objective: To assess the efficacy, retention and tolerability of adjunctive cenobamate (CNB), and to identify factors that might predict these outcomes in the clinical treatment of focal epilepsies.

Methods: This multicentre, retrospective cohort study included all patients who began CNB treatment between October 2020 and April 2023 at seven participating epilepsy centres. Baseline and follow-up data were collected from patients' medical records, covering clinical characteristics and outcome data such as seizure frequency, dosing of CNB, physician-assessed Clinical Global Impression of Change, treatment-emergent adverse events (TEAEs), CNB retention and reasons for discontinuation.

Results: A total of 234 patients [mean age 40.7 ± 14 years, median 40 years, range 11-82 years; five adolescents under 18 years; 99 (42.3%) males] were analysed. The mean epilepsy duration at study entry was 23.2 ± 14.5 years (median 21 years, range 0.75-63 years), with the average age of epilepsy onset being 17.5 ± 13.0 years (median 17 years, range 0.1-71 years). The patients were taking a mean of 2.6 ± 0.8 (median 3) anti-seizure medications (ASMs) before starting CNB, and had failed a mean of 6 ± 3.3 (median 6) of further ASMs in the past. CNB exposure ranged from 5 to 1162 days, amounting to a total exposure time of 264.7 years. The retention rate was 92.6% at 3 months, 87.2% at 6 months and 77.8% at 12 months. At 3 months, 52.6% achieved a 50% seizure reduction, with 14.5% reporting seizure freedom; by 12 months, 47.7% maintained a 50% response rate and 11.9% were seizure-free. No significant differences in responder rates were observed based on sex, aetiology, seizure localisation, number of ASMs or target dose. The mean maximum CNB dose was 236.7 ± 97.4 mg (median 200 mg, range 12.5-450 mg), with 28 patients (12.0%) titrated up to 400 mg or above. During CNB treatment, 43.6% of patients were able to discontinue, and a further 24.4% were able to reduce the dose of a concomitant ASM. During CNB treatment, 144 patients (61.5%) experienced TEAEs. The most common TEAEs were sedation (n = 84, 35.9%), dizziness (n = 58, 24.8%) and ataxia (n = 23, 9.8%).

Conclusions: CNB showed a relatively high and clinically useful 50% responder rate of 47.7% and an overall retention of 77.8% at 1 year. We were unable to identify specific predictors for response and retention, indicating that CNB may be beneficial for patients with a history of multiple failed ASMs, a high number of concomitant ASMs and any localisation or aetiology of focal epilepsy.

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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
审稿时长
6-12 weeks
期刊介绍: CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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