Cenobamate as an Early Adjunctive Treatment in Drug-Resistant Focal-Onset Seizures: An Observational Cohort Study

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY CNS drugs Pub Date : 2024-08-03 DOI:10.1007/s40263-024-01109-9

Yaroslav Winter, Raya Abou Dargham, Susana Patiño Tobón, Sergiu Groppa, Sven Fuest

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Abstract

Background and Objectives

Cenobamate (CNB) is a new antiseizure medication (ASM) to treat drug-resistant, focal-onset seizures. Data on its use in early therapy lines are not yet available, and clinicians frequently consider CNB to be a later ASM drug choice. We investigated the efficacy and safety of CNB as an early adjunctive treatment in drug-resistant, focal-onset seizures.

Methods

The study population were patients with drug-resistant, focal-onset seizures who were initiated with CNB after they did not respond to two or three lifetime ASMs, including all prior and concomitant ASMs. These patients were matched (1:2) by sex, age, and seizure frequency to controls who were initiated with any ASM other than CNB. All participants participated in the Mainz Epilepsy Registry. We evaluated the retention rate after 12 months of CNB and after each new adjunctive ASM in the control group. In addition, seizure freedom and the response rate (reduction of seizure frequency by ≥ 50% from baseline) after 12 months were estimated.

Results

We included 231 patients aged 44.4 ± 15.8 years. Of these, 33.3% (n = 77) were on CNB, 19.0% (n = 44) on valproate (VPA), 17.3% (n = 40) on lacosamide (LCS), 16.4% (n = 38) on levetiracetam (LEV), and 13.9% (n = 32) on topiramate (TPM). The highest retention rate after 12 months since the beginning of the early adjunctive therapy was observed on CNB (92.0%), compared with LCS (80.0%), LEV (73.3%), VPA (68.2%), or TPM (62.5%) (p < 0.05). Seizure freedom and response rate were also the best on CNB (19.5% and 71.4%, respectively) compared with other ASMs (8.3% and 52.5%, respectively; p < 0.05). No significant differences in adverse events between CNB and other ASMs were observed.

Conclusions

Our study provides evidence that CNB is an effective ASM with a good safety profile in the early therapy lines of drug-resistant, focal-onset seizures. This data should support medical decision making in the management of patients with refractory epilepsy.

Clinical Trial ID

NCT05267405.

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塞诺巴马特作为药物耐药性局灶性发作的早期辅助治疗：观察性队列研究

背景和目的塞诺巴马特（CNB）是一种新型抗癫痫药物（ASM），用于治疗耐药的局灶性癫痫发作。目前还没有关于该药在早期治疗方案中使用的数据，临床医生通常将 CNB 作为后期抗癫痫药物的选择。我们研究了 CNB 作为耐药、局灶性发作的早期辅助治疗药物的有效性和安全性。研究对象为耐药、局灶性发作患者，他们在接受了两到三次终生 ASM（包括所有先前和伴随的 ASM）治疗无效后开始使用 CNB。这些患者按性别、年龄和癫痫发作频率与对照组进行了配对（1:2），对照组患者开始使用除 CNB 以外的任何 ASM。所有参与者都参加了美因茨癫痫登记。我们评估了对照组患者在接受 CNB 治疗 12 个月后以及每次使用新的辅助 ASM 后的保留率。此外，我们还估算了 12 个月后的发作自由度和反应率（发作频率比基线降低≥50%）。其中，33.3%（n = 77）服用 CNB，19.0%（n = 44）服用丙戊酸钠（VPA），17.3%（n = 40）服用拉科萨胺（LCS），16.4%（n = 38）服用左乙拉西坦（LEV），13.9%（n = 32）服用托吡酯（TPM）。早期辅助治疗开始 12 个月后，CNB（92.0%）的保留率最高，而 LCS（80.0%）、LEV（73.3%）、VPA（68.2%）或 TPM（62.5%）的保留率最低（p <0.05）。与其他 ASMs（分别为 8.3% 和 52.5%；p < 0.05）相比，CNB 的癫痫发作自由度和反应率也是最好的（分别为 19.5% 和 71.4%）。结论我们的研究提供了证据，证明 CNB 是一种有效的 ASM，在耐药、局灶性癫痫发作的早期治疗中具有良好的安全性。这些数据应能为难治性癫痫患者的医疗决策提供支持。

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

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.