DECREASE study: A European pool‐analysis of patients with significant reductions in concomitant antiseizure medications in cenobamate Early Access Programs

OBJECTIVE: To evaluate the effectiveness and tolerability of cenobamate in patients with a significant reduction in concomitant antiseizure medication (ASM) in European cenobamate Early Access Programs (EAPs). METHOD: Anonymized patient data from real-world studies/registries associated with European cenobamate EAPs were pooled. Patients were included if they had significantly reduced their concomitant drug load (i.e., converted to cenobamate monotherapy or reduced from multiple to one concomitant ASM) between baseline and the last visit. Effectiveness, tolerability, and dosage of cenobamate were evaluated. Responses according to therapeutic regimen at last visit were studied. RESULTS: Of 694 patients within cenobamate EAPs, 75 (10.7%) met the inclusion criteria (mean age 39.5 years [range 19-65]). At baseline, the median number of prior ASMs was 10 (interquartile range [IQR] 6-13); 46 patients (61.3%) were taking two, 23 (30.7%) were taking three, and six (8%) were taking four concomitant ASMs at baseline. At the last visit, seven patients (9.3%) were converted to monotherapy and 68 (90.7%) were receiving one concomitant ASM. The median cenobamate dosage at last visit was 300 mg (IQR 200-350). Median cenobamate follow-up was 22 months; 73 patients (97%) had at least 1 year of follow-up and one discontinued cenobamate at 1 year. Twenty-five patients (33.3%) were seizure-free at last visit; 51 (68%) had a ≥50% reduction in seizure frequency. The seizure-freedom rate was numerically, but not significantly, higher in patients converted to monotherapy (57.1%) versus those receiving one concomitant ASM (30.9%; p = 0.16). Cenobamate plus clobazam was the most effective combination. Adverse events (AEs) were reported in 55/75 patients (73.3%); the most common were somnolence (30.7%), dizziness/vertigo (28%), and fatigue (26.7%). No AEs led to treatment discontinuation. SIGNIFICANCE: Cenobamate demonstrated good effectiveness and tolerability in a population of patients within European EAPs who achieved a significant reduction of concomitant ASM. PLAIN LANGUAGE SUMMARY: People with highly drug-resistant epilepsy often need to take several antiseizure medications at the same time. Combined data from European Early Access Programs show that about 10% of people treated with cenobamate were able to stop all other antiseizure medications or reduce treatment to cenobamate plus one other medication. Despite this simplification of treatment, one-third of these patients became seizure-free and more than two-thirds experienced at least a 50% reduction in seizure frequency. Within this group, no patients stopped cenobamate because of side effects.