TOPLINE:

Cenobamate was linked to a greater reduction in seizures at 6 months than brivaracetam, perampanel, or lacosamide in patients with drug-resistant focal epilepsy, a new real-world analysis showed. However, there was also a higher rate of adverse events (AEs) for cenobamate than for the other three antiseizure medications (ASMs) in the comparative study.

METHODOLOGY:

• A pooled analysis of four retrospective medical record-review datasets included nearly 2000 distinct antiseizure medication prescriptions from patients aged 16 years or older with focal epilepsy (median age, 42 years; 53% women) treated at 71 epilepsy centers between 2017 and 2024.
• Overall, 48% of prescriptions were for brivaracetam, 30.5% for perampanel, 12% for lacosamide, and 10% for cenobamate as adjunctive therapies.
• The primary outcome was the responder rate at 6 months, defined as a 50% or greater reduction in seizure frequency from baseline. Secondary outcomes included the 12-month responder rate, seizure freedom at 6 and 12 months, and the 12-month retention rate.
• Safety assessment involved monitoring for AES, including somnolence/fatigue, central nervous system (CNS) symptoms, vertigo/dizziness, behavioral changes, and gastrointestinal symptoms.

TAKEAWAY:

• Use of cenobamate was associated with significantly increased responder rates at 6 months compared to use of brivaracetam (odds ratio [OR], 0.2; P < .001), perampanel (OR, 0.3; P < .001), or lacosamide (OR, 0.3; P < .001), with the association remaining greater at 12 months (ORs, 0.2 for all comparisons; P < .001 for all).
• At 6 months, cenobamate was also linked to significantly higher odds of seizure freedom for 3 or more months than brivaracetam (OR, 0.4; P = .001) but not to perampanel or lacosamide. However, cenobamate was linked to a significantly higher likelihood of seizure freedom for 6 or more months at 12 months than brivaracetam (OR, 0.3; P < .001), perampanel (OR, 0.4; P = .01), or lacosamide (OR, 0.4; P = .02).
• Although cenobamate was linked to higher 12-month retention rates than brivaracetam (OR, 0.4; P < .001) and perampanel (OR, 0.6; P = .047), the difference was not significant compared to lacosamide.
• AEs were most frequent with cenobamate (58%), followed by perampanel (32%), brivaracetam (30.5%), and lacosamide (15%). The most commonly reported AEs for cenobamate were somnolence/fatigue (28%), CNS symptoms (21%), and vertigo/dizziness (20%).

IN PRACTICE:

“Further prospective studies and pragmatic head-to-head trials are warranted to confirm these findings, define optimal treatment sequencing, and best ASM combination strategies,” the investigators wrote.

SOURCE:

The study was led by Emanuele Cerulli Irelli, MD, PhD, Sapienza University of Rome in Rome, Italy. It was published online on February 09 in JAMA Neurology.

LIMITATIONS:

The retrospective study design introduced potential residual confounding , and potential selection bias could not be excluded. AEs were reported using unadjusted rates. Additionally, analyzing seizure frequency as a categorical variable may have limited the level of detail captured from the datasets.

DISCLOSURES:

No funding information was provided for the study. Several investigators reported having financial or other ties with various pharmaceutical companies, which are fully listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.