Tackling the Unmet Therapeutic Needs in Nonsurgical Treatments for Epilepsy

Steriade, Claude; French, Jacqueline

doi:10.1001/jamaneurol.2022.2635

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Symptomatic pharmacological treatment with antiseizure medications (ASMs) by different monotherapies or combinations remains the mainstay for people with epilepsy (PWE), but there are still unmet needs for both the treatment‐responsive population (facing tolerability and adherence issues) and treatment‐resistant patients (needing better or more targeted efficacy) 4 …”

Section: Introductionmentioning

confidence: 99%

“…2,3 Symptomatic pharmacological treatment with antiseizure medications (ASMs) by different monotherapies or combinations remains the mainstay for people with epilepsy (PWE), but there are still unmet needs for both the treatment-responsive population (facing tolerability and adherence issues) and treatment-resistant patients (needing better or more targeted efficacy). 4 Over the past decades, the number of available ASMs has progressively increased, and new drugs with either improved or new mechanisms of action have been marketed. 5,6 Compared with first-generation ASMs, most of them are characterized by more favorable pharmacokinetics and drug interaction profiles.…”

Section: Introductionmentioning

confidence: 99%

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A real‐world comparison among third‐generation antiseizure medications: Results from the COMPARE study

Roberti,

Di Gennaro,

Anzellotti

et al. 2023

Epilepsia

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ObjectiveThere are few comparative data on the third‐generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives.MethodsThis multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add‐on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan–Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models.ResultsA total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)‐naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17–3.29) and PER groups (HR = 1.64, 95% CI = 1.06–2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71–16.61), as well as PER‐treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05–2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01–.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV‐naïve (OR = 10.32, 95% CI = 1.55–68.78) versus men. PER (OR = 6.93, 95% CI = 3.32–14.44) and BRV in LEV‐naïve patients (OR = 6.80, 95% CI = 2.64–17.52) had a higher chance of AEs than LCM.SignificanceComparative evidence from real‐world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A real‐world comparison among third‐generation antiseizure medications: Results from the COMPARE study

Roberti,

Di Gennaro,

Anzellotti

et al. 2023

Epilepsia

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Drug resistance in epilepsy

Perucca

White

et al. 2023

The Lancet Neurology

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

Roberti,

Assenza,

Bisulli

et al. 2024

Epilepsia

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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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Tackling the Unmet Therapeutic Needs in Nonsurgical Treatments for Epilepsy

Abstract: This Viewpoint discusses unmet therapeutic needs among patients with epilepsy and evaluates the trajectory of treatment development.

Cited by 3 publications

References 10 publications

A real‐world comparison among third‐generation antiseizure medications: Results from the COMPARE study

A real‐world comparison among third‐generation antiseizure medications: Results from the COMPARE study

Drug resistance in epilepsy

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

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