Real-world utilization of Cenobamate as adjunct therapy in office-based neurology: practical tips and insights for titration

Abstract

Introduction: Epilepsy poses significant management challenges, particularly in patients with refractory epilepsy where conventional antiseizure medications (ASMs) are ineffective. Cenobamate (CNB), a recently approved third-generation ASM, has shown unprecedented efficacy as an adjunctive therapy in clinic-based practice. However, to date, its use by office-based neurologists in Germany remains relatively limited. One reason for this is its perceived complexity and false perception as a medication of last resort. This study focuses on the logistics of German care pathways, CNB titration, and ASM combinations in a first cohort of office-based outpatients. It also gives a glimpse into which ASMs are being used in the office-based setting in comparison to population and clinic-based data sources.

Methods: The cohort comprised 55 patients from two office-based outpatient practices (Niedergelassene) in Berlin (n = 25) and Hamburg (n = 30). All patients had a history of refractory epilepsy despite optimal treatment with existing ASMs. Patients were initiated on CNB from the month of approval (June 2021) to March 2023. Data on prior ASM usage were collated alongside clinical data, which included seizure frequency and drug load reduction outcomes to March 2025.

Results: Prior to CNB initiation, patients at both office-based practices had similar levels of 1-2 concurrent ASMs (Berlin 80%; Hamburg 77%). The most common ASMs were voltage-gated sodium channel blockers (VGSC), Levetiracetam (LEV)/Brivaracetam (BRV) synaptic vesicle protein 2A (SV2A) inhibitors, and Perampanel (PER). CNB titration was configured into a quarterly office-based outpatient schedule. All patients had seizure reductions in-line with published and real-world evidence, and were compliant.

Discussion and conclusion: CNB is a valuable adjunctive therapy suitable for refractory epilepsy outpatients attending office-based neurologists. A slow titration schedule helped mitigate most side effects. Despite differences to clinic-based practice, in office-based outpatient practice CNB can be broadly used. It can be prescribed to patients on conventional therapy who are still having seizures and have failed two or more other ASMs. By reporting experiences of CNB titration, seizure, and drug load reduction outcomes in office-based neurology, this study will give German office-based outpatient neurologists evidence to support both CNB and other third-generation ASM use in their practice.

Keywords: Cenobamate; antiseizure medication; epilepsy care pathways; epileptologist; neurologist; outpatients; refractory epilepsy; seizure freedom.

Figure 1

Demographic information for the office-based outpatient cohort, n=55. (a) Spectrum of cognitive abilities reflected diversity within the studied population; (b) age distribution was heterogenous; (c) patients had taken between 3 and 18 failed ASMs or ASM combinations (mean=7.4) prior to CNB initiation; (d) all patients were diagnosed with focal epilepsy but some patients had more than one additional diagnosis. Although LGS is a DEE, they are shown separated in the figure. ASM, anti-seizure medication; CNB, Cenobamate; n, number of patients; LGS, Lennox-Gastaut syndrome; DEE, developmental and epileptic encephalopathy.

Figure 2

Changes in CNB dose and seizure frequency over time for the office-based outpatient cohort, n=55. (a) All patients initiated CNB with 12.5 mg/d and over time dose was increased until positive seizure outcome or discontinuation; (b) seizure reduction across the whole cohort at timepoints February 2022, March 2023, June 2023, and March 2025. Green represents patients who were seizure-free or had a seizure reduction >50%. Orange represents patients with seizure reduction <50%, beige represents patients with no change. By March 2025 more than half of patients were seizure-free or had >50% reduction. CNB, Cenobamate; mg/d, milligram per day; n, number of patients.

Figure 3

ASM use for the office-based outpatient cohort prior to CNB initiation (n=55). (a) 54% patients were taking either 1 or 2 ASMs concurrently, the remainder patients were taking 3 or more ASMs concurrently; (b) the most common prior combinations for patients with a minimum 2 concurrent ASMs were VGSC + SV2A blockers (44%), PER + VGSC (20%), PER + SV2A (18%), and PER + SV2A + VGSC (16%). The remaining combinations were given to <10% patients; (c) when compared with clinic-based patients and IQVIA™ nationwide population data, the office-based outpatient cohort had a higher prescription of VGSCs, PER, and GABA modulators. These patterns may reflect distinct office-based outpatient treatment strategies. ASM, anti-seizure medication; CNB, Cenobamate; MoA, mechanism of action; n, number of patients; VPA, Valproate; TPM, Topiramate; CA, calcium channel modulator; GABA*, γ-Aminobutyric acid (Clobazam, Primidone/PB, Clonazepam); PER, Perampanel; SV2A, synaptic vesicle protein 2A; VGSC, voltage-gated sodium channel.