Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study

Beltrán-Corbellini, Álvaro; Romeral-Jiménez, María; Mayo, Pablo; Sánchez-Miranda Román, Irene; Iruzubieta, Pablo; Chico-García, Juan Luis; Parra-Díaz, Paloma; García-Morales, Irene; Toledano, Rafael; Aledo-Serrano, Ángel; Gil-Nagel, Antonio

doi:10.1016/j.seizure.2023.07.026

Cited by 13 publications

(21 citation statements)

References 22 publications

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“…The open-label extension data and some real-world studies support this view [20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 60%

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Steinhoff,

Georgiou,

Dietmann

et al. 2024

JCM

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Objective: Cenobamate is approved by the European Medicine Agency for the treatment of adult patients with epilepsy (PWEs) with ongoing focal-onset seizures despite appropriate treatment with at least two established antiseizure medications. Pivotal trials and post-marketing real-world observational studies suggest high efficacy with unusually high seizure-free rates. The authors sought to investigate the plasma levels of cenobamate under steady-state conditions in seizure-free versus non-responding PWEs, and in PWEs who experienced adverse events versus those who did not. Methods: Blood samples were collected from adult PWEs who were treated with adjunct cenobamate under steady-state conditions. Daily doses, concomitant medications, efficacy, and tolerability were assessed. The plasma cenobamate levels of seizure-free versus non-responding PWEs and between PWEs with and those without clinical adverse events were compared. Results: Samples from 101 PWEs were included. Thirty-six PWEs were seizure-free and 65 were non-responders. In 31 PWEs, adverse events were apparent, whereas in the remaining 70, no tolerability issues were reported. A linear correlation was found between the daily doses (range: 100 mg–400 mg) and the plasma levels (3.8 mg/L–54.6 mg/L). Neither the daily doses nor the plasma levels differed significantly between the investigated subgroups. The main reason for this result was that the individual therapeutic ranges varied widely: seizure freedom and adverse effects were observed alongside low doses and plasma levels in some PWEs. Conversely, there were examples of PWEs who did not respond or who reported no tolerability issues at high doses or plasma levels. Conclusions: To evaluate the individual therapeutic range and to better understand the influence of other drugs in cases where concomitant medications are used, the therapeutic drug monitoring of cenobamate may be useful. A general therapeutic range cannot be defined.

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“…The open-label extension data and some real-world studies support this view [20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 60%

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Steinhoff,

Georgiou,

Dietmann

et al. 2024

JCM

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“…23,24 On the other hand, while the Italian experts also acknowledged that seizure freedom could sometimes be achieved with doses of cenobamate as low as 50-100 mg/day, 24 we recommend comedication be managed in order to achieve the maximal potential effectiveness. Last, according to our experience, slower titration does not appear to improve tolerability, and this is supported by data from clinical trials and real-world evidence 21,25 ; however, individualizing therapy is recommended. As in other therapeutic scenarios with ASMs, when achieving seizure freedom after the addition of cenobamate, the risks and benefits of transitioning to monotherapy could be considered.…”

Section: Discussionmentioning

confidence: 79%

“…Patients with highly drug‐resistant focal epilepsy might benefit from a higher dose of cenobamate (>200 mg). Slower titration does not appear to improve tolerability, as seen in clinical trials and real‐world evidence, 21 , 25 while co‐medication management appears to be a key aspect of improving tolerability 20 , 21 , 22 ; nevertheless, individualization of therapy is recommended.…”

Section: Resultsmentioning

confidence: 99%

“…Evidence from clinical trials and real‐world studies suggests that most adverse impacts on patients receiving cenobamate in combination with other ASMs can be effectively managed by decreasing the dose of, or completely discontinuing, the concomitant ASMs. 19 , 20 , 21 , 22 Tapering of concomitant ASMs is an acknowledged method of reducing AEs in patients taking multiple ASMs including cenobamate. 17 Reducing the dose or discontinuing concomitant ASMs has been shown to resolve AEs spontaneously in some patients, 20 while not doing so is thought to exacerbate AEs.…”

Section: Introductionmentioning

confidence: 99%

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Spanish consensus on the management of concomitant antiseizure medications when using cenobamate in adults with drug‐resistant focal seizures

Carreño,

Gil‐Nagel,

Serratosa

et al. 2024

Epilepsia Open

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ObjectiveCenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate dose for maximal potential effectiveness while avoiding or minimizing drug‐related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug‐resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate.MethodsA three‐stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration.ResultsThe expert panel agreed that tailored titration and close follow‐up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period.SignificanceCenobamate is an effective ASM with a dose‐dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co‐medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co‐medication in cenobamate‐treated patients with DRE and a high drug load.Plain Language SummaryPatients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug‐resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate.

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“…. Furthermore, several real-world studies substantiate its significant benefits in treating many drug-resistant epilepsy patients (Beltran-Corbellini et al, 2023;Schmitz et al, 2023). Despite the broad therapeutic potential of cenobamate in managing epilepsy, attention should be directed towards its safety.…”

mentioning

confidence: 99%

Safety assessment of cenobamate: real-world adverse event analysis from the FAERS database

Chen,

Fang,

Zhao

et al. 2024

Front. Pharmacol.

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Objective:This study aims to analyze adverse drug events (ADEs) associated with cenobamate from the FAERS database, covering the third quarter of 2020 to the second quarter of 2023.Methods:Data related to cenobamate-associated ADEs from the third quarter of 2020 to the second quarter of 2023 were collected. After standardizing the data, various signal quantification techniques, including ROR, MHRA, BCPNN, and MGPS, were employed for analysis.Results:Among 2535 ADE reports where cenobamate was the primary suspected drug, 94 adverse reactions involving 11 different System Organ Class (SOC) categories were identified through the application of four signal quantification techniques. More specifically, neurological disorders and injuries resultant from complications are frequent adverse reactions associated with cenobamate.Conclusion:Our research findings align with established results, affirming the favorable safety profile of cenobamate. Effective prevention of adverse reactions induced by cenobamate can be achieved through the establishment of efficient blood concentration monitoring and dose adjustments.

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Cenobamate in patients with highly refractory focal epilepsy: A retrospective real-world study

Cited by 13 publications

References 22 publications

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Cenobamate Plasma Levels in Patients with Epilepsy: Correlation with Efficacy and Tolerability?

Spanish consensus on the management of concomitant antiseizure medications when using cenobamate in adults with drug‐resistant focal seizures

Safety assessment of cenobamate: real-world adverse event analysis from the FAERS database

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