Effect of Cenobamate on Cognition in Patients with Drug-Resistant Epilepsy with Focal Onset Seizures: An Exploratory Study
Pedro J Serrano-Castro,
Teresa Ramírez-García,
Pablo Cabezudo-Garcia
et al.
Abstract:Background and Objective
Most second and third generation antiseizure medications (ASMs) are associated with cognitive adverse events, which are a major concern for patients. However, the profile of cognitive adverse events differs between ASMs. This study investigated the effects of cenobamate on cognition in patients with drug-resistant epilepsy (DRE) within the Spanish Expanded Access Program (EAP).
Methods
This was a retrospective, observational study. Inclusion cri… Show more
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.
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.
ObjectiveThis 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.MethodsThis 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.ResultsA 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.SignificanceAdjunctive 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.
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