Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

One-year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability.

Perampanel, a non-competitive antagonist of the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, is the most recent antiepileptic drug available in Spain, marketed in January 2014. It was initially approved by the European Medicines Agency as adjunctive treatment for partial-onset seizures in patients 12 years and older, but recently also for primary generalized tonic-clonic seizures. Although clinical trials provide essential information about the drug, they do not reflect daily clinical practice. This retrospective study shows the initial experience with perampanel in 11 Spanish hospitals during its first year post-commercialisation. All patients who started perampanel treatment were included, but efficacy and tolerability were only assessed in those patients with a minimum follow-up period of six months. In total, 256 patients were treated with perampanel before September 2014, and 253 had an observational period of one year. After six months, 216/256 patients (84%) continued on perampanel and 180/253 (71.1%) completed one year of treatment. The mean number of previous antiepileptic drugs used was 6.83 and the median number of concomitant antiepileptic drugs was 2. The mean perampanel dose was 7.06 mg and 8.26 mg at six and 12 months, respectively. The responder rate was 39.5% and 35.9% at both follow-up points, respectively. Adverse events were experienced by 91/253 (35.5%) and resulted in withdrawal in 37 (14.6%). The most common adverse events were somnolence, dizziness, and irritability. We found no significant differences between concomitant use of enzyme-inducing and non-inducing antiepileptic drugs, regarding efficacy, adverse effects, or withdrawals. Irritability was not influenced by concomitant use of levetiracetam, relative to other drugs, but was more frequently observed in patients with a history of psychiatric problems or learning disabilities.