Lacosamide Shows Long-term Efficacy for Newly Diagnosed Epilepsy

The long-term use of lacosamide monotherapy for adults with newly-diagnosed epilepsy appeared effective and was generally well tolerated, according to new research.

A multinational team of investigators from UCB Pharma conducted a large-scale, double-blind trial of lacosamide and compared it to controlled-release carbamazepine as first therapy treatment in newly-diagnosed epilepsy patients aged 16 years or older. The investigators aimed to explore the long-term outcomes of these 2 monotherapy treatments. The patients all had newly diagnosed focal or generalized tonic-clonic seizures without clear focal or generalized origin.

A total of 444 patients received lacosamide while 442 received controlled-release carbamazepine. Lacosamide and carbamazepine were initiated at 100 mg/day or 200 mg/day, respectively. Then the medications were titrated to a target dose of 200 mg/day for lacosamide or 400 mg/day for carbamazepine. The doses were increased again to 400/600 mg/day for lacosamide or 800/1200 mg/day for carbamazepine if needed, the researchers wrote.

Patients who reached 6 months without any seizures at their final dose level were eligible to continue for 12 months to achieve seizure freedom or discontinue after experiencing a seizure.

The lacosamide patients experienced a slightly longer median duration of treatment (n = 630 days) compared to the carbamazepine patients (n = 589 days).

Among lacosamide patients, 50.8% (95% CI, 46.2 — 55.4%) were seizure free for 12 months, while 47% (95% CI, 42.2 – 51.7%) remained seizure free after 24 months. In the controlled-release carbamazepine group, 54.9% of patients (95% CI, 50.3 – 59.6%) were seizure free for 12 months and that dropped to 50.9% (95% CI, 46.0 – 55.7%) after 24 months.

There were patients who chose to continue treatment for 24 months, including 177 lacosamide patients and 164 carbamazepine patients. Of those, 98.9% of the lacosamide patients and 99.4% of the carbamazepine patients had at least 12 months without seizures. Additionally, 84.2% of lacosamide patients and 82.9% of carbamazepine patients achieved 24 months of seizure freedom, according to the study authors.

The study reported that there were fewer patients in the lacosamide group than the carbamazepine cohort who experienced drug-related treatment-emergent adverse events or discontinued treatment for to treatment-emergent adverse events overall. Some of the adverse events included headache, dizziness, fatigue, nasopharyngitis, nausea, somnolence, hypercholesterolemia, and gamma-glutamyltransferase increase.

The investigators reported a longer median time to discontinuation due to lack of efficacy or treatment-emergent adverse events in the lacosamide cohort (191 days) than in the carbamazepine group (115 days).

Of the 886 study participants, about a quarter had no comorbid conditions, while a third had 1-2 conditions, and the rest had 3 or more comorbid conditions at baseline. The most common of these was hypertension, the study authors noted.

When the investigators stratified the efficacy data by comorbid conditions, they learned that the incidence of drug-related treatment-emergent adverse events and discontinuations due to treatment-emergent adverse events increased by number of comorbid conditions; it was also consistently lower in patients in the lacosamide cohort compared to the carbamazepine cohort.

The abstract, “Long-term safety and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy,” was published on the American Epilepsy Society website.