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Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain.

Casas-Fernández C, Martínez-Bermejo A, Rufo-Campos M, Smeyers-Durá P, Herranz-Fernández JL, Ibáñez-Micó S, Campistol-Plana J, Alarcón-Martínez H, Campos-Castelló J - Drugs R D (2012)

Bottom Line: Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events.A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation.The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy.

View Article: PubMed Central - PubMed

Affiliation: Neuropediatric Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

ABSTRACT

Background: The safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients.

Objective: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. DesignMethods: The trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT®; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1-2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ≥1 other AED. Treatment response to lacosamide was determined by assessing the change in seizure frequency after 3 months of lacosamide therapy. Responders were defined as patients who achieved a seizure frequency reduction of >50%. Tolerability was assessed by the reporting of adverse effects, laboratory testing, and electroencephalography recordings.

Results: Lacosamide was dosed at a mean of 6.80 ± 2.39 mg/kg/day. After 3 months of lacosamide therapy, 62.3% of patients achieved a >50% reduction in seizure frequency, with complete seizure suppression being reported in 13.8% of patients. Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events. In ten patients, instability, difficulty walking, an inability to relate to subjective elements, and blurred vision or dizziness were reported. A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation. The symptoms were markedly different in each patient, preventing determination of a causal factor(s).

Conclusions: The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy. Further evaluation in a randomized, controlled trial is needed to validate the efficacy in this population and to fully investigate the adverse effects described here. We recommend an initial dose of 1-2 mg/kg/day, uptitrated to 6-9 mg/kg/day over 4-6 weeks.

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Characteristics of patients enrolled in the study (N = 130)
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Tab1: Characteristics of patients enrolled in the study (N = 130)

Mentions: Data on patient demographics and clinical characteristics are summarized in table I. Overall, 130 cases of refractory epilepsy were analyzed in patients under 16 years of age (mean age 8.01 ± 4.25 years; range 6 months to 16 years). Epilepsies of a symptomatic origin were due to perinatal pathology (25.9%), malformations of cortical development [MCD] (19.7%), other cerebral malformations (14.8%), neuroectodermal disorders (12.3%), central nervous system infections (8.6%), metabolic diseases (6.1%), genetic alterations (4.9%), mesial sclerosis (3.7%), cerebrovascular disease (2.4%), and presumed autoimmune disease [Rasmussen’s syndrome] (2.4%). A high percentage of patients (81.5%) had cognitive problems, of whom 56 (43%) had serious retardation. The epileptic syndrome was identified in 26 cases, which included West syndrome (eight cases); Dravet syndrome (six cases); continuous spike-wave during slow sleep syndrome [CSWS] (five cases); Lennox syndrome, autosomal dominant nocturnal frontal lobe epilepsy, or Rasmussen’s syndrome (two cases each); and Dulac devastating epilepsy (one case).Table I


Efficacy and tolerability of lacosamide in the concomitant treatment of 130 patients under 16 years of age with refractory epilepsy: a prospective, open-label, observational, multicenter study in Spain.

Casas-Fernández C, Martínez-Bermejo A, Rufo-Campos M, Smeyers-Durá P, Herranz-Fernández JL, Ibáñez-Micó S, Campistol-Plana J, Alarcón-Martínez H, Campos-Castelló J - Drugs R D (2012)

Characteristics of patients enrolled in the study (N = 130)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585895&req=5

Tab1: Characteristics of patients enrolled in the study (N = 130)
Mentions: Data on patient demographics and clinical characteristics are summarized in table I. Overall, 130 cases of refractory epilepsy were analyzed in patients under 16 years of age (mean age 8.01 ± 4.25 years; range 6 months to 16 years). Epilepsies of a symptomatic origin were due to perinatal pathology (25.9%), malformations of cortical development [MCD] (19.7%), other cerebral malformations (14.8%), neuroectodermal disorders (12.3%), central nervous system infections (8.6%), metabolic diseases (6.1%), genetic alterations (4.9%), mesial sclerosis (3.7%), cerebrovascular disease (2.4%), and presumed autoimmune disease [Rasmussen’s syndrome] (2.4%). A high percentage of patients (81.5%) had cognitive problems, of whom 56 (43%) had serious retardation. The epileptic syndrome was identified in 26 cases, which included West syndrome (eight cases); Dravet syndrome (six cases); continuous spike-wave during slow sleep syndrome [CSWS] (five cases); Lennox syndrome, autosomal dominant nocturnal frontal lobe epilepsy, or Rasmussen’s syndrome (two cases each); and Dulac devastating epilepsy (one case).Table I

Bottom Line: Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events.A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation.The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy.

View Article: PubMed Central - PubMed

Affiliation: Neuropediatric Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

ABSTRACT

Background: The safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients.

Objective: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. DesignMethods: The trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT®; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1-2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ≥1 other AED. Treatment response to lacosamide was determined by assessing the change in seizure frequency after 3 months of lacosamide therapy. Responders were defined as patients who achieved a seizure frequency reduction of >50%. Tolerability was assessed by the reporting of adverse effects, laboratory testing, and electroencephalography recordings.

Results: Lacosamide was dosed at a mean of 6.80 ± 2.39 mg/kg/day. After 3 months of lacosamide therapy, 62.3% of patients achieved a >50% reduction in seizure frequency, with complete seizure suppression being reported in 13.8% of patients. Adverse effects occurred in 39 patients (30%), but no dose-response relationship was observed in terms of these events. In ten patients, instability, difficulty walking, an inability to relate to subjective elements, and blurred vision or dizziness were reported. A total of 13 patients discontinued treatment - in five of these patients, symptom intensity remained unchanged despite dose reduction, which led to treatment discontinuation. The symptoms were markedly different in each patient, preventing determination of a causal factor(s).

Conclusions: The results of this study provide preliminary evidence for the efficacy of lacosamide in children with refractory epilepsy. Further evaluation in a randomized, controlled trial is needed to validate the efficacy in this population and to fully investigate the adverse effects described here. We recommend an initial dose of 1-2 mg/kg/day, uptitrated to 6-9 mg/kg/day over 4-6 weeks.

Show MeSH
Related in: MedlinePlus