Support for lacosamide as a monotherapy in newly diagnosed epilepsy
medwireNews: Lacosamide could be suitable as a monotherapy for adults with newly diagnosed epilepsy, say researchers.
The drug, which is already approved in the USA and Europe as an adjunctive treatment, met the study’s non-inferiority criteria when compared with controlled-release carbamazepine, a standard reference comparator, report the study authors in The Lancet Neurology.
In a comment accompanying the study, Francesco Brigo (University of Verona, Italy) says that “after a long and strenuous journey for lacosamide,” the researchers have provided “robust evidence supporting its use as monotherapy for newly diagnosed epilepsy.”
He adds: “Use of these findings to approve lacosamide would add this drug to the few other treatments already available for such indication.”
In the full set of 444 patients who received at least one dose of lacosamide, 74% had no seizures during 6 months of follow-up, compared with 70% of 442 patients who received at least one dose of carbamazepine. This translated into estimated on-treatment efficacies of 89.9% and 91.1%, respectively, on Kaplan-Meier analysis, giving an absolute difference of 1.3% and relative difference of 6.0%, which met the corresponding predefined noninferiority criteria of 12% and 20% differences.
In line with clinical practice, stepwise drug dose increments, based on seizure control and tolerability, were used in the randomized trial. Lacosamide was started at 100 mg/day and uptitrated to 200 mg/day, while carbamazepine was started at 200 mg/day and uptitrated to 400 mg/day.
Further uptitrations to 400 and 600 mg/day for lacosamide and to 800 and 1200 mg/day for carbamazepine were allowed within the first 6 months. For patients who remained seizure-free during the first 6 months, treatment was continued for a further 6 months at the last dose. The researchers note that most of the patients in both treatment groups continued taking the first target drug dose for the duration of the study.
Noninferiority was not assessed at 12 months, but the researchers note that the percentage of patients free from seizures at this point remained similar, at 78% with lacosamide and 83% with carbamazepine.
The two treatment groups also did not differ significantly in terms of treatment-emergent adverse events, which occurred in 74% of patients receiving lacosamide and 75% receiving carbamazepine, with serious event rates of 7% and 10%, respectively. Events most commonly leading to withdrawal were dizziness and rash in the lacosamide group and for the carbamazepine group, rash, increased γ-glutamyl transferase concentration, increased alanine aminotransferase concentration, and somnolence.
Noting that monotherapy is the preferred option for patients aged 65 years or older, Michel Baulac (Hôpital de la Pitié-Salpêtrière, Paris, France) and fellow researchers highlight that, while Kaplan-Meier efficacy estimates were similar for patients of this age, numerically more of those receiving lacosomide completed 6 months of treatment seizure-free and on the first dose level than did those receiving carbamazepine. And of the most frequently reported adverse events, only falls occurred at a 5% or greater incidence among those taking lacosomide than carbamazepine.
“Lacosamide is a non-enzyme-inducing antiepileptic drug with a predictable pharmacokinetic profile and low potential for interactions with other drugs, including the contraceptive pill,” concludes the team.
“Our findings suggest that lacosamide is a suitable treatment option for patients with newly diagnosed epilepsy.”
By Lucy Piper
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