LACONORTE study: Efficacy and security of lacosamide as first add-on therapy for focal-onset epilepsy in real-life setting
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.
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2022, Epilepsy and BehaviorCitation Excerpt :Several studies examined the issue of associating lacosamide with SCBs or non-sodium channel blockers (NSCBs), reporting either no difference [1,2] or lower tolerability and effectiveness [3,4], therefore the issue remains open to debate. The use of lacosamide in typical patients with focal-onset epilepsy is clearly successful in real-life practice [5,6]. By contrast information on the use of lacosamide in populations of patients with drug-refractory epilepsy, who are often affected by neurological and intellectual disabilities, is scant at best, despite around one-fourth of patients with epilepsy having an intellectual disability [7].
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2021, Epilepsy and BehaviorCitation Excerpt :Indeed, it is possible to individualize titration and maintenance dosages to optimize efficacy and tolerability, to perform a longer observation period and to focus attention on special populations, including elderly subjects and/or with comorbidities. Although the long-term use of LCM monotherapy has been assessed in an open-label extension to SP902 after conversion to monotherapy (where 107 PwE had a longest monotherapy duration of ≥24 months), there are also several smaller open-label and retrospective studies in Europe have included patients receiving LCM, usually as conversion monotherapy [7–14]. Here we report results from a retrospective chart review of PwE treated with LCM (first add-on regimen or substitution of first ASM) at tertiary Epilepsy Centre in Italy, with the aim to assess its effectiveness and tolerability in routine clinical practice.
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2021, Life SciencesCitation Excerpt :In addition, adverse effects are more often registered in drug-resistant epileptic patients [43]. In adult and pediatric patients, common side effects target the central nervous system and include dizziness, headache, anxiety, somnolence, nausea and diplopia [44], with no significant differences when used in monotherapy or adjunctive therapy [17,18]. A retrospective study with data from clinical practice, showed that the main causes of lacosamide discontinuation are its adverse effects, with dizziness at the forefront as the one with the highest prevalence rate, occurring in up to 55% of patients who received a 600 mg total daily dose [45].
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2021, Epilepsy and BehaviorCitation Excerpt :The secondary outcome variables included the terminal 6-month seizure remission and percentages of discontinuation due to a lack of efficacy and tolerability. Safety variables included the incidence and type of adverse reactions, as well as their intensity as mild, moderate, or severe, according to the patient’s subjective perception of severity [11]. Adverse reactions leading to LCM discontinuation were also noted.