Elsevier

Epilepsy Research

Volume 145, September 2018, Pages 51-54
Epilepsy Research

LACONORTE study: Efficacy and security of lacosamide as first add-on therapy for focal-onset epilepsy in real-life setting

https://doi.org/10.1016/j.eplepsyres.2018.05.011Get rights and content

Highlights

  • Lacosamide is efficacious and safe as first add-on therapy y focal onset epilepsy.

  • Responder rate was 91.8%, 64.4% were seizure free and 24.7% converted to monotherapy.

  • No severe adverse events were reported. Most of them were mild and transient.

  • Results were independent of age, antiepileptic drug combination and type of seizure.

Abstract

Rationale

Many patients with epilepsy need a second antiepileptic drug (AED), due either to inefficacy or side effects of the first tried one. We evaluated the efficacy and safety of lacosamide (LCM) as first add-on therapy in the real-life setting.

Methods

LACONORTE is a multicenter, retrospective, one-year study. Patients with focal epilepsy on monotherapy with another AED who were started on lacosamide as first add-on therapy were included. Clinical data was obtained at 3, 6 and 12 months and then analyzed.

Results

Seventy-three patients (48.6% men) with a mean age of 50.3 and a median duration of the epilepsy of 3.0 years (range 0–65) were included. At 1 year, 91.8% were responders (with at least 50% reduction in the number of seizures) and 64.4% of all patients and 75.8% of those with secondary generalization were seizure-free. Fifteen patients (20.5%) had adverse events (AE), most of them were transient and no severe AEs were reported. LCM was withdrawn in 2 patients due to intolerance and in 1 patient because of inefficacy. Neither side effects nor withdrawal seemed to be related to total dose or to escalating regimes. Seventy patients (95.9%) continued on LCM after the last visit (median dose 200 mg/day, ranging 100–400). Eighteen (24.7%) converted to monotherapy during the 12-month period, 83.3% of them remaining seizure-free.

Conclusions

These results of real-life setting show LCM to be efficacious and safe when used as first add-on therapy for focal-onset epilepsy. Most adverse events were mild and/or transient.

Introduction

The goal of the antiepileptic drug (AED) therapy is to achieve seizure freedom while avoiding treatment related adverse effects (AE). The first AED monotherapy results to be successful in less than 50% of patients. Thus, most patients will require changes to their initial treatment regime to obtain seizure control or to reduce drug related adverse events (AEs), which include switching monotherapy regimens or initiating AED polytherapies (Kwan and Brodie, 2000).

Lacosamide (LCM) is a third-generation AED that selectively enhances sodium-channel slow inactivation. It is indicated as monotherapy and adjunctive therapy in patients with focal onset seizures (FOS), at doses up to 400 mg/day. Three clinical trials established the efficacy, safety, and tolerability of adjunctive lacosamide against placebo (Ben-Menachem et al., 2007, Chung et al., 2010, Halasz et al., 2009, Sake et al., 2010). Another study demonstrated the non-inferiority of lacosamide compared to carbamazepine-controlled-release in the treatment of FOS as first-line monotherapy (Baulac et al., 2017).

Most of the patients included in adjunctive therapy studies had long-term treatment-refractory epilepsies and a high frequency of seizures. The 84% of them were treated with at least two concomitant AEDs and almost 80% of them had tried four or more AEDs prior to inclusion (Chung et al., 2010).

However, lacosamide plays a different role in real life setting. It is frequently used in patients with less treatment-refractory epilepsies and often added to only one concomitant AED. Moreover, flexible dosing, as opposed to the fixed 400 mg/day dose in the clinical trials, allows seizure control while minimizing AEs.

The objective of this work in a clinical practice setting was to evaluate the seizure control and tolerability of lacosamide as first add-on therapy in adults with FOS.

Section snippets

Study design and participants

LACONORTE was a multicenter, retrospective, non-interventional study conducted at seven Neurology units in Northern Spain. After informed consent, all patients meeting the inclusion criteria were consecutively enrolled.

Adult patients with FOS, with and without secondary generalization, and receiving only one baseline AED were eligible for inclusion, if lacosamide was initiated as first add-on therapy according to their physician’s criteria.

Physicians filled a case report form for each patient,

Patient disposition

Case reports from 98 patients were collected. Twenty-five patients were excluded, 17 due to incomplete one-year data and 8 because they were seizure free when LCM was started. A total of 73 patients were finally included in the study.

LCM retention rate was 95.9%, i.e., 70 patients continued on lacosamide after the 12-month period and the drug had been withdrawn in 3 patients.

Demographics and epilepsy characteristics

The baseline demographics and clinical characteristics of patients are summarized in Table 1. The mean age was 50.3 years

Discussion

This real-life setting study assessed the efficacy, safety, and tolerability of lacosamide in patients treated with only one AED prior to inclusion. Lacosamide was used as a rather early adjunctive treatment with a broad range of baseline AED monotherapies. In this study, 91.8% of patients were responders and 64.4% achieved seizure freedom after 12 months of LCM treatment. It is worth mentioning the 97.0% response rate among patients with secondary generalized seizures.

The observed response

Limitations

LACONORTE is a retrospective and single-group study with a relatively small and very heterogeneous sample, which limits the ability to obtain strong conclusions. Large randomized control studies would be needed in this aspect. Reporting bias caused by patients spontaneously reporting their seizure frequency is another potential limitation.

Conclusions

Despite the limitations, the results of this real-world setting study suggest that lacosamide is an efficacious, safe and well tolerated AED when used as firs add-on therapy in patients with FOS. Moreover, these results seem to be independent of the age, baseline AED and the type of seizure (with or without secondary generalization).

Conflict of interest

None of the authors has any conflict of interest to disclose.

References (14)

There are more references available in the full text version of this article.

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