Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

IF 6.6 1区医学 Q1 CLINICAL NEUROLOGY

Epilepsia Pub Date : 2024-08-14 DOI:10.1111/epi.18091

Roberta Roberti, Giovanni Assenza, Francesca Bisulli, Giovanni Boero, Laura Canafoglia, Valentina Chiesa, Carlo Di Bonaventura, Giancarlo Di Gennaro, Maurizio Elia, Edoardo Ferlazzo, Alfonso Giordano, Angela La Neve, Claudio Liguori, Stefano Meletti, Francesca Felicia Operto, Nicola Pietrafusa, Monica Puligheddu, Patrizia Pulitano, Eleonora Rosati, Ilaria Sammarra, Elena Tartara, Giampaolo Vatti, Flavio Villani, CNB EAP Italy Study Group, Emilio Russo, Simona Lattanzi

{"title":"Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program","authors":"Roberta Roberti, Giovanni Assenza, Francesca Bisulli, Giovanni Boero, Laura Canafoglia, Valentina Chiesa, Carlo Di Bonaventura, Giancarlo Di Gennaro, Maurizio Elia, Edoardo Ferlazzo, Alfonso Giordano, Angela La Neve, Claudio Liguori, Stefano Meletti, Francesca Felicia Operto, Nicola Pietrafusa, Monica Puligheddu, Patrizia Pulitano, Eleonora Rosati, Ilaria Sammarra, Elena Tartara, Giampaolo Vatti, Flavio Villani, CNB EAP Italy Study Group, Emilio Russo, Simona Lattanzi","doi":"10.1111/epi.18091","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 236 subjects with a median age of 38 (Q<sub>1</sub>–Q<sub>3</sub> = 27–49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q<sub>1</sub>–Q<sub>3</sub> = 2.50–4.47) at baseline to 2.50 (Q<sub>1</sub>–Q<sub>3</sub> = 1.67–3.50) at 12 months (<i>p</i> < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel.</p>\n </section>\n \n <section>\n \n <h3> Significance</h3>\n \n <p>Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.</p>\n </section>\n </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"65 10","pages":"2909-2922"},"PeriodicalIF":6.6000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18091","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epilepsia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/epi.18091","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy.

Methods

This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses.

Results

A total of 236 subjects with a median age of 38 (Q₁–Q₃ = 27–49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q₁–Q₃ = 2.50–4.47) at baseline to 2.50 (Q₁–Q₃ = 1.67–3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel.

Significance

Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.

Abstract Image

查看原文本刊更多论文

对局灶性癫痫发作患者辅助使用仙诺巴马特：意大利扩大使用计划的启示。

研究目的本研究旨在评估仙诺巴马酯辅助治疗的有效性/耐受性、同时服用的抗癫痫药物（ASM）负荷的变化以及局灶性癫痫患者临床反应的预测因素：这是一项回顾性研究，在参与意大利扩大准入计划的 21 个中心进行。疗效结果包括保留率和应答率（基线癫痫发作频率降低≥50%和100%）。耐受性/安全性结果包括因不良事件（AEs）而中断治疗的比率及其发生率。药物总负荷量化为同时服用的 ASM 数量和定义的日总剂量 (DDD)。此外，还根据其作用机制和药代动力学相互作用对同时服用的 ASM 进行了分类，以进行探索性亚组分析：共纳入 236 名受试者，中位年龄为 38（Q1-Q3 = 27-49）岁。12个月后，西诺巴马特的保留率为78.8%，应答者为57.5%。在3、6、9和12个月时，前3个月的无发作率分别为9.8%、12.2%、16.3%和14.0%。在接受氯巴扎姆治疗的受试者中，有反应者的比例较高，但差异无统计学意义。在 236 名受试者中，133 人共发生了 223 例 AE，8.5% 的受试者因此停用了氯巴马特。12 个月时，分别有 42.6% 和 4.3% 的受试者减少了一种或两种并发 ASM。所有同时服用的 ASM 的总 DDD 中位数从基线时的 3.34（Q1-Q3 = 2.50-4.47）降至 12 个月时的 2.50（Q1-Q3 = 1.67-3.50）（P 有学意义：在难以治疗的成人局灶性癫痫患者中，辅用仙诺巴马特与减少癫痫发作频率和并发ASM的负担有关。除了氯巴扎铵有良好的趋势外，相关的 ASM 类型并不影响疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Epilepsia 医学-临床神经学

CiteScore

10.90

自引率

10.70%

发文量

319

审稿时长

2-4 weeks

期刊介绍： Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.