Profile of lacosamide and its role in the long-term treatment of epilepsy: a perspective from the updated NICE guideline

Neuropsychiatric Disease and Treatment Dovepress open access to scientific and medical research R eview Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Profile of lacosamide and its role in the long-term treatment of epilepsy: a perspective from the updated NICE guideline This article was published in the following Dove Press journal: Neuropsychiatric Disease and Treatment 5 April 2013 Number of times this article has been viewed Vanessa Delgado Nunes 1 Laura Sawyer 2 Julie Neilson 1 Grammati Sarri 1 J Helen Cross 3,4 National Clinical Guideline Centre, Royal College of Physicians, London, UK; 2 Symmetron Limited, Elstree, UK; 3 UCL Institute of Child Health, Great Ormond Street Hospital for Children, London, UK; 4 Young Epilepsy, Lingfield, UK 1 Aim: The goal of antiepileptic treatment is to achieve seizure freedom or seizure control. The aim of this paper is to review the evidence for the use of lacosamide for adjunctive treatment of refractory focal seizures with or without secondary generalization, within the scope of the 2012 update of the Clinical Guideline published by the National Institute for Health and Clinical Excellence (NICE). Methods: Clinical evidence for the use of lacosamide and other antiepileptic drugs (AEDs) was systematically reviewed, evaluated, and presented to the Guideline Development Group. Only randomized clinical trials were included. Outcomes of clinical efficacy (seizure freedom, 50% reduction in seizure frequency, time to first seizure, time to 12-month remission, treatment withdrawal, and time to treatment withdrawal), experience of adverse events, and cognitive and quality of life outcomes were reviewed. A decision model was built to weigh the clinical benefits of each adjunctive AED, measured by seizure control and seizure reduction, compared with the harm from adverse events, as measured by withdrawals from treatment due to adverse events. Results: Lacosamide was included as part of the recommended AEDS to be used in tertiary epilepsy centers. The evidence review showed that more participants who received lacosamide as an adjunctive treatment had at least a 50% reduction in seizure frequency compared with those taking placebo. However, more participants on lacosamide were found to experience adverse events and withdrawal from treatment compared with those on placebo. The cost-effectiveness analysis showed that compared with placebo, the benefits gained from adjunctive lacosamide were modest and uncertain, whereas the costs were significantly high. Compared with other AEDs licensed for adjunctive therapy in focal seizures, lacosamide was associated with fewer quality-adjusted life years and higher costs. Therefore, the Guideline Development Group noted that the balance of benefit and harm needs to be carefully monitored in all patients. Keywords: focal seizures, anti-epileptic drug, adjunctive therapy, clinical guideline Introduction Correspondence: Vanessa Delgado Nunes National Clinical Guideline Centre, Royal College of Physicians, 11 St Andrews Place, NW1 4LE, London, UK Tel +44 020 3075 1277 Fax +44 020 7631 5097 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/NDT.S32081 Powered by TCPDF (www.tcpdf.org) Epilepsy is defined as a neurological condition characterized by recurrent epileptic seizures unprovoked by any immediately identifiable cause. An epileptic seizure is the clinical manifestation of an abnormal and excessive discharge of a set of neurons in the brain.1 Epileptic seizures should be viewed as a symptom with many different causes and not as a single disease entity. Epilepsy is therefore more accurately termed the epilepsies. Diagnosis can be challenging, making accurate prevalence estimates difficult. With a prevalence of active epilepsy of 5–10 cases per 1000,2 epilepsy has been estimated to affect between 362,000 and 415,000 people in England, with a further Neuropsychiatric Disease and Treatment 2013:9 467–476 467 © 2013 Delgado Nunes et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Delgado Nunes et al 5%–30% (up to another 124,500 people) misdiagnosed with epilepsy.3 Consequently, a physician or pediatrician with expertise in epilepsy should diagnose and manage the condition. Focal seizures, by definition, arise from networks limited to one hemisphere.4 They are the most common seizure type in adults and children. The mainstay of treatment for epilepsy are the antiepileptic drugs (AEDs), taken daily to prevent the recurrence of epileptic seizures. Seizure freedom remains the goal of therapy, although in some individuals, optimal seizure control may be more achievable. Treatment success has been most recently defined by the International League Against Epilepsy as a seizure-free duration that is at least three times the longest seizure-free interval prior to starting the new treatment, with a sustained response over 12 months.5 The 2004 guideline from the National Institute of Health and Clinical Excellence (NICE) on the management of the epilepsies in adults and children was partially updated in January 2012, with regard to drug management. Update of the 2004 guideline was driven mainly by the fact that a further five AEDs had become licensed for use in the UK for the treatment of epilepsy in the intervening years, as well as by the publication of the Standard and New Antiepileptic Drug (SANAD) trial.6 Lacosamide is licensed in the UK for adjunctive treatment of refractory focal seizures with or without secondary generalization. Although, like other AEDs (eg, carbamazepine, lamotrigine), it acts on voltage-gated sodium channels, it is believed to do so by enhancing slow inactivation rather than stabilizing fast inactivation.7 It was included in the systematic review of clinical evidence and original cost-effectiveness analysis of different pharmacological interventions for epilepsy in adults with refractory focal seizures in the 2012 update. Here, we review the evidence for lacosamide alongside other AEDs for the treatment of refractory focal seizures, collected as part of the guideline update. Methods Clinical evidence methods The Guideline Development Group (GDG) comprised a psychiatrist (chair), two patient members, two pediatric neurologists (one of whom was the clinical adviser), two adult neurologists, a general practitioner, a pediatrician, a clinical pharmacologist, and two specialist nurses. The GDG followed the standard NICE methods in the development of this guideline.8 This involved systematically 468 Powered by TCPDF (www.tcpdf.org) submit your manuscript | (...truncated)