Add‐on treatment with cenobamate is already effective at low doses in refractory focal epilepsy: A prospective observational study

Abstract

Abstract:ObjectiveCenobamate, a novel ASM with a dual mechanism of action, has been shown in pivotal trials to significantly improve seizure control in treatment‐resistant focal epilepsy. We aimed to evaluate whether these promising results could be confirmed in a real‐world setting with a follow‐up period of up to 12 months.MethodsPatients from a tertiary epilepsy centre who received cenobamate add‐on between June 2021 to October 2023 were followed up prospectively at 3, 6 and 12 months after treatment initiation for assessment of seizure outcomes and treatment‐related adverse events.ResultsThe clinical cohort included 112 adult patients with 30% non‐lesional cases and a wide spectrum of epileptogenic lesions underlying refractory focal epilepsy. We observed a significant reduction in monthly seizure frequency of all seizure types already after 3 months of treatment at a median cenobamate dose of 100 mg/day. 46% of patients were responders with a ≥ 50% seizure reduction, 26% had a ≥ 75% seizure reduction, and 9% became seizure free. Among the 74 patients with available follow‐up of 12 months, the responder rates reached 55%, 35% and 19% for ≥ 50%, ≥ 75% and 100% of seizure reduction, respectively.After 3 months of treatment, 38% of patients reported adverse effects, mainly (84%) mild to moderate in intensity. Adjustment of comedication allowed successful management of adverse effects in 32% of patients. At a group level, there was no correlation between the cenobamate daily dose and the incidence of adverse effects.SignificanceWe found a clinically relevant response to cenobamate already at a low daily dose of 100 mg also in a patient cohort with a higher degree of drug resistance than in pivotal trials. Our prospectively collected data provide real‐world evidence for high efficacy and good tolerability of the drug although no standardized treatment protocol or comparison with a control group was applied.

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

“…This mean dose was almost identical to that reported by Villanueva et al 19 After 6 and 12 months, the mean daily doses were in the range of 250 mg, as in other publications. 15,19,23 In line with previous results of the pivotal and postmarketing studies, 9,12,15,17,19,20,[22][23][24][25][26][27][28] our data confirm that CNB is a highly efficacious ASM.…”

“…Novitskaya et al performed a study with an almost identical design and achieved similar results. 28 Other previous prospective surveys were open-label follow-up studies of pivotal randomized controlled trials 17,22,23 or the open-label Phase-III trial that addressed safety as the primary outcome criterion. 15 The mean daily dose of CNB of 175.2 mg after 3 months reflected that some PWE were still in the up-titrating process.…”

“…Our results are very similar to other real-world experiences from various countries and centers, regardless of whether the study was monocentric or multicentric. 15,17,19,20,[22][23][24][25][26][27] Similarly, in a prospective study by Novitskaya et al, 28 seizure freedom was reported in 5% of patients after 6 months and in 19% after 1 year. Furthermore, in their study the ≥50% responder rates were 40% and 55%, respectively.…”

“…13,18,21 Indeed, in line with the pivotal trials, the openlabel extension data and real-world studies supported this view. [17][18][19][20][22][23][24][25][26][27][28] The Kork Epilepsy Center is one of the leading tertiary referral epilepsy centers in Germany. 29 We had the privilege of participating in two pivotal trials with CNB, 12,15 providing us with firsthand experience in the practical administration and the potential benefits that CNB offers.…”

Therapeutic strategies during cenobamate treatment initiation: Delphi panel recommendations

“…Of note, early efficacy starting at cenobamate 25 mg/day has previously been observed. 19 Reactive down-titration of concomitant benzodiazepines is recommended when an individual experiences somnolence or fatigue. For individuals taking phenobarbital or phenytoin, drug monitoring is suggested.…”