Brivaracetam effectiveness and tolerability in older and younger adults with epilepsy: EXPERIENCE, a pooled analysis of international data from retrospective studies.

This analysis assessed the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years of age) and younger (≥16 to <65 years of age) adults with epilepsy. This was a subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of individual patient records from multiple independent, non-interventional studies of patients with epilepsy starting BRV in Australia, Europe, and the United States. Included patients had ≥6 months of follow-up data.

Therapeutic strategies during cenobamate treatment initiation: Delphi panel recommendations.

The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically on ⩾2 ASMs, increasing the potential for drug-drug interactions.

The cenobamate KORK study-A prospective monocenter observational study investigating cenobamate as an adjunctive therapy in refractory epilepsy, with comparisons to historical cohorts treated with add-on lacosamide, perampanel, and brivaracetam.

Objective: In Europe, cenobamate has been approved for use as an adjunctive therapy in adult patients with epilepsy (PWE) with focal-onset seizures (FOS) who have not responded satisfactorily to treatment with at least two antiseizure medications (ASMs). Pivotal trials and real-world observational studies have demonstrated a high efficacy of cenobamate, even in very difficult-to-treat epilepsies. Our aim was to investigate the efficacy of add-on cenobamate in adult PWE who were prospectively monitored.

Evaluating the Inheritance Risk: Epilepsy Prevalence among Offspring of Adults with Epilepsy in a Tertiary Referral Epilepsy Center.

While significant strides have been made in comprehending the pathophysiology and treatment of epilepsy, further investigation is warranted to elucidate the factors impacting its development and transmission, particularly within familial contexts. This study sought to explore the prevalence and risk factors associated with epilepsy in the offspring of patients with epilepsy who were treated at a tertiary epilepsy center. Adult patients with confirmed epilepsy (PWE) receiving outpatient care were consecutively enrolled, starting from January 2021 to January 2023.

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

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.

Technical note: preliminary surgical experience with a new implantable epicranial stimulation device for chronic focal cortex stimulation in drug-resistant epilepsy.

Purpose: This study is to report some preliminary surgical considerations and outcomes after the first implantations of a new and commercially available implantable epicranial stimulation device for focal epilepsy.

Methods: We retrospectively analyzed data from clinical notes. Outcome parameters were as follows: wound healing, surgery time, and adverse events.

Psychiatric assessment prior to and after switch from levetiracetam to brivaracetam.

Purpose: Brivaracetam is often used as an alternative to levetiracetam in patients with epilepsy (PWE) encountering efficacy issues or adverse events with levetiracetam. This study evaluated the psychological status of PWE who were switched from levetiracetam to brivaracetam due to psychiatric tolerability concerns in comparison to those who remained on levetiracetam.

Methods: We used various psychological assessments including the Symptom Checklist SCL-90-R, the Beck Depression Inventory-II, and the adverse event profile.

Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world: 12-month subgroup data from the international EXPERIENCE pooled analysis.

Objective: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies.

Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months.

Critical flicker fusion in patients with epilepsy under antiseizure medication.

Objective: Critical flicker frequency (CFF) and flicker frequency (FF) are used as indicators for the neurotoxic adverse events of drugs in pharmacology. In this pilot study, we investigated whether patients with epilepsy (PWE) treated with various antiseizure medications (ASM) had significantly different CFFs compared with healthy controls. In addition, we investigated the appropriateness of CFF as an objective measurement tool in PWE who reported adverse events according to the adverse event profile (AEP).

PERPRISE: A prospective non-interventional study of PERampanel as only adjunctive treatment in patients with PRImary or SEcondarily generalized tonic-clonic seizures: First interim analysis.

Objective: To report the interim results of the PERPRISE study (Study 509; NCT04202159), which is evaluating perampanel as the only adjunctive anti-seizure medication (ASM) in adults with focal to bilateral tonic-clonic seizures (FBTCS) or primary generalized tonic-clonic seizures (GTCS).

Methods: PERPRISE is an ongoing 12-month multicenter, prospective, observational, non-interventional study of perampanel in a real-world setting in Germany. Patients are aged ≥18 years with FBTCS or GTCS due to focal or idiopathic generalized epilepsy.

Effectiveness and Tolerability of 12-Month Brivaracetam in the Real World: EXPERIENCE, an International Pooled Analysis of Individual Patient Records.

Background And Objective: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population.

Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Failure to use new breakthrough treatments for epilepsy.

Despite the approval of ~20 additional antiseizure medications (ASMs) since the 1980s, one-third of epilepsy patients experience seizures despite therapy. Drug-resistant epilepsy (DRE) is associated with cognitive and psychiatric comorbidities, socioeconomic impairment, injuries, and a 9.3-13.

Real-world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study.

Objective: Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes.

Methods: In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers.

Loss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies.

Background: De novo missense variants in KCNQ5, encoding the voltage-gated K channel K7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms.

Onset of efficacy and adverse events during Cenobamate titration period.

Objectives: Cenobamate is an antiseizure medication (ASM) approved in Europe as adjunctive therapy for adults with inadequately controlled focal seizures. This post hoc analysis reports onset of efficacy and characterizes time to onset, duration, and severity of the most common treatment-emergent adverse events (TEAEs) during cenobamate titration.

Materials & Methods: Adult patients with uncontrolled focal seizures taking 1 to 3 concomitant ASMs were randomized to receive adjunctive cenobamate or placebo (double-blind studies C013 and C017) or cenobamate (open-label study C021).

Long-term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures.

Background And Objectives: To evaluate long-term efficacy (percent seizure frequency reduction and responder rates), safety, and tolerability of adjunctive cenobamate (CNB) in an open-label extension (OLE) of the randomized, double-blind, placebo-controlled study.

Methods: Patients (aged 18-70 years) with uncontrolled focal seizures despite treatment with 1-3 antiseizure medications who completed the 18-week double-blind study (n = 360) could enter the OLE, where they underwent a 2-week blinded conversion to CNB (target dose, 300 mg/d; min/max, 50/400 mg/d).

Results: Three hundred fifty-five patients were included in the OLE safety population (265 originally randomized to CNB, 90 originally randomized to placebo), and 354 were included in the OLE modified intent-to-treat population.

Efficacy and safety of adjunctive cenobamate: Post-hoc analysis of study C017 in patients grouped by mechanism of action of concomitant antiseizure medications.

Purpose: To assess how efficacy and safety outcomes were affected when cenobamate was co-administered with antiseizure medications (ASMs) that use either sodium channel blocker (SCB) or non-sodium channel blocker (non-SCB) mechanisms of action (MoAs) in patients with uncontrolled focal seizures.

Methods: An exploratory post-hoc analysis of a randomized, double-blind, placebo-controlled clinical study (YKP3089C017) was conducted. Baseline concomitant ASMs were grouped as either those that employed an SCB or non-SCB MoA.

Long-term individual retention with cenobamate in adults with focal seizures: Pooled data from the clinical development program.

Objective: We determined retention on open-label cenobamate therapy in the clinical development program to assess the long-term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.

Methods: Data from two randomized, controlled cenobamate studies and one open-label safety and pharmacokinetic study were pooled. Based on the percentage of participants remaining on treatment, retention rates were estimated using Kaplan-Meier survival analyses.

Practical guidance for the management of adults receiving adjunctive cenobamate for the treatment of focal epilepsy-expert opinion.

Clinical trial results have demonstrated that adjunctive cenobamate (CNB) substantially decreases seizure frequency in adults with uncontrolled focal onset seizures with an acceptable and well-identified safety profile. This manuscript summarizes an expert panel's recommendations regarding optimized CNB treatment of epilepsies with focal onset seizures. Cenobamate, when slowly titrated to the target maintenance dose, represents an effective new antiseizure medication (ASM) with a comparatively high rate of seizure freedom relative to existing treatment options.

PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice.

The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness assessments included 50% responder rate (≥ 50% reduction in seizure frequency from baseline) and seizure freedom rate (no seizures since at least the prior visit); in PWE with status epilepticus, response was defined as seizures under control.