Post-marketing Experience with Cenobamate in the Treatment of Focal Epilepsies: A Multicentre Cohort Study

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

In randomised controlled trials, adjunctive cenobamate (CNB) has been shown to reduce seizure frequency in patients with drug-resistant focal epilepsy. Studies conducted real-world settings provide valuable complementary data further characterise the drug's profile. To assess efficacy, retention and tolerability of (CNB), identify factors that might predict these outcomes clinical treatment epilepsies. This multicentre, retrospective cohort study included all who began CNB between October 2020 April 2023 at seven participating epilepsy centres. Baseline follow-up were collected from patients' medical records, covering characteristics outcome such as frequency, dosing CNB, physician-assessed Clinical Global Impression Change, treatment-emergent adverse events (TEAEs), reasons for discontinuation. A total 234 [mean age 40.7 ± 14 years, median 40 range 11–82 years; five adolescents under 18 99 (42.3%) males] analysed. The mean duration entry was 23.2 14.5 years (median 21 0.75–63 years), average onset being 17.5 13.0 17 0.1–71 years). taking a 2.6 0.8 3) anti-seizure medications (ASMs) before starting had failed 6 3.3 6) ASMs past. exposure ranged 5 1162 days, amounting time 264.7 years. rate 92.6% 3 months, 87.2% months 77.8% 12 months. At 52.6% achieved 50% reduction, 14.5% reporting freedom; by 47.7% maintained response 11.9% seizure-free. No significant differences responder rates observed based on sex, aetiology, localisation, number or target dose. maximum dose 236.7 97.4 mg 200 mg, 12.5–450 mg), 28 (12.0%) titrated up 400 above. During treatment, 43.6% able discontinue, 24.4% concomitant ASM. 144 (61.5%) experienced TEAEs. most common TEAEs sedation (n = 84, 35.9%), dizziness 58, 24.8%) ataxia 23, 9.8%). showed relatively high clinically useful an overall 1 year. We unable specific predictors retention, indicating may be beneficial history multiple ASMs, any localisation aetiology

Language: Английский

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Exploring the Effectiveness of Adjunctive Cenobamate in Focal Epilepsy: A Time-Based Analysis

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

A growing body of evidence supports the effectiveness cenobamate (CNB). This study aimed to assess clinical response add-on CNB through a time-to-event approach and explore potential contribution concomitant classes antiseizure medications (ASMs) improve use. is subgroup analysis larger retrospective, multicenter on adults with focal-onset seizures participating in Italian Expanded Access Program at five pre-established centers. The primary endpoint was time-to-baseline seizure count; secondary endpoints included rates response, freedom (defined as no seizures' occurrence since least previous follow-up visit), treatment discontinuation, adverse events (AEs). Data 92 participants were extracted, median age 44 (first quartile (Q1)–third (Q3): 29.25–50.75) years. number recorded during 90-day baseline reached by 59/92 (64.1%) subjects 12-month follow-up. higher, but not statistically significant probability reaching count shown subgroups taking sodium channel blockers (SCBs) (hazard ratio [HR] 2.75; 95% confidence interval [CI] 0.79–9.61, p = 0.112) both SCBs GABAergics (HR 1.48; CI 0.43–5.09, 0.536) compared without SCBs. At 12 months, seizure-freedom, discontinuation 42.0%, 13.6%, 23.9%, respectively. total 47/92 (51.1%) experienced AEs (mainly somnolence, dizziness, balance disorders) time 61 (Q1–Q3: 30–101) days. There risk treated those 2.24; 0.51–9.82, 0.286 HR 1.40; 0.31–6.39, 0.661, respectively) main limitations are retrospective design small sample size. added new insights currently available about real-world CNB. Explorative estimates suggested favorable trends for SCBs, who seemed reach experience less frequently later than other ASMs. Further studies needed identify best combinations ASMs maximize control tolerability.

Language: Английский

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Real‐world effectiveness and tolerability of cenobamate in drug‐resistant epilepsy: A retrospective analysis of the patients included into the Early Access Programs (EAP) in Germany, France, and United Kingdom

Epilepsia Open, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Abstract Objective Investigate real‐world outcomes in drug‐resistant epilepsy (DRE) patients treated with cenobamate as adjunctive treatment to other antiseizure medications (ASMs) within the Early Access Programs (EAP) Germany, France, and United Kingdom. Methods DRE adults uncontrolled focal‐onset seizures were included from 19 hospitals participating EAP this retrospective study. Data sourced clinical records. Participants evaluated at baseline, 1 months, 3 months start, 3, 6, 12 after maintenance. The primary effectiveness endpoint was 50% responder rate, defined reduction seizure frequency ≥50%. Results collected 298 who received least one dose of cenobamate; efficacy on 216 data available. At median duration 22.2 years, 41.9% had previous surgery, including vagus nerve stimulation, a nine previously failed ASMs. number seizures/month 8.8. After maintenance, rate (primary endpoint) 49.3%; percentage baseline 49.1%. A total 100%, ≥90%, ≥75% reported 13.6%, 20.0%, 33.6% patients, respectively. Both steadily increased during observation period. 6‐month seizure‐free 24.2%. retention assessed by Kaplan–Meier decreased 96.6% 1‐month start 69.7% 12‐month Adverse Drug Reactions (ADRs) occurred 30.9% asthenia, dizziness, somnolence being most frequent; majority mild‐to‐moderate resolved period; three (1.0%) experienced seven serious ADRs, all titration. Significance In study, demonstrated be an effective option for people even multiple ASMs or failure surgery. Plain Language Summary This study involved epilepsy, continued despite using two (ASMs). Patients (Ontozry) Program An allows receive promising new drugs under supervision before they are commercially 6 49.3% their cut half more, 13.6% became seizure‐free. undesirable reaction cenobamate, mostly resolved; frequent somnolence.

Language: Английский

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Increase of Brivaracetam serum concentration with introduction of Cenobamate

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 1, 2025

Introduction Cenobamate is a new antiseizure medication approved for polytherapy of focal epilepsy with complex hepatic metabolism and effects on liver enzymes. So far, data are limited regard to possible interactions other medications. We here report serum levels Brivaracetam, SV2-agent modulating presynaptic neurotransmitter release. Methods Retrospective analysis Brivaracetam concentrations introduction as constant baseline in 19 patients epilepsy. Statistical using paired Fisher´s exact t-Test. Results New lead statistically significant increase mean by 27%. This was infrequently accompanied adverse effects. Discussion pre-existing regimen containing leads considerably increases probably related inhibition CYP2C19. needs be taken into account when interpreting changes treatment efficacy, but also relating potential vs. newly introduced treatment.

Language: Английский

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Cenobamate: A Review in Focal-Onset Seizures

CNS Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

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Effectiveness and safety of adjunctive cenobamate in people with focal‐onset epilepsy: Interim results after 24‐week observational period from the BLESS study

Epilepsia, Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Abstract Objective Cenobamate is an antiseizure medication (ASM) with a dual mechanism of action that was recently approved for the treatment focal seizures in adults. This analysis aimed to describe outcomes at 12 and 24 weeks after starting cenobamate therapy real‐world setting. Methods BLESS [NCT05859854] ongoing, observational, retrospective prospective cohort study evaluate effectiveness safety adjunctive adults uncontrolled epilepsy. Subgroup performed subjects 2 3 previous ASMs (early users) those >3 (late users). Results The second interim included 388 participants median (interquartile range) age 43.0 (31.0–54.0) years. They had 6.0 (4.0–9.0) prior 7.2 (3.0–20.6) monthly baseline. seizure frequency reduced by 59.9% (19.2%–87.3%) from baseline weeks; 229 (59.0%) ≥50% reduction, 44 (11.3%) showed sustained freedom. proportion taking ≤2 concomitant increased 217 (56.5%) 239 (65.7%) weeks. Among early users ( n = 76, 19.6%), reduction 78.0% (50.0–97.1%), 76.3% response rate. adverse drug reactions (ADRs) 5.3% 23.4% late users. most frequent ADRs were somnolence, dizziness, balance disorder; occurrence ADRs, 63.5% maintained prescribed dose, 5.2% permanently discontinued treatment. Significance effective reducing setting manageable profile. also burden both

Language: Английский

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Impact of lifetime antiepileptic drug history on cenobamate efficacy in adults with focal epilepsy

Seizure, Journal Year: 2024, Volume and Issue: 125, P. 94 - 98

Published: Dec. 20, 2024

Language: Английский

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