Health Technology Assessment of Lacosamide as Adjunctive Therapy for Partial-Onset Epileptic Seizures

Epilepsy is a neurological disorder that disrupts the normal transmission of electrical signals in the brain and is characterised by abnormal electrical neuronal activity resulting clinically in unprovoked recurring seizures. Partial-onset seizures are those that involve only a portion of the brain at seizure onset. The prevalence of epilepsy varies between 4 and 8 cases per 1,000 individuals in developed countries (Hauser, 1990), and partial seizures are the predominant type of epileptic seizures (Kotsopoulos et al., 2002). Epileptic seizures are associated with significant morbidity, impaired quality of life, mortality, and are a primary driver of hospital admissions and health care costs. A literature review reported an increased mortality risk for people with epilepsy as compared with the general population (Hitiris et al., 2007). A bottom-up, prevalence-based, cost-of-illness analysis estimated the costs of epilepsy from a societal perspective in the 25 European Union member countries, plus Iceland, Norway, and Switzerland (Pugliatti et al., 2007). The estimated total cost of the disease in Europe was € 15.5 billion in 2004, indirect costs related to productivity loss being the single most important cost category (€ 8.6 billion). The total cost per case was € 2,000–11,500 and the estimated cost per European individual was € 33. Treatment with anti-epileptic drugs (AEDs) is the mainstay of therapy for people with epilepsy and treatment tends to begin with monotherapy (Brodie & Dichter, 1997). Firstgeneration AEDs available before 1980 (e.g. carbamazepine, phenytoin, phenobarbital, valproic acid) are used first-line as monotherapy (Perucca & Meador, 2005). Although many patients respond to their first treatment, more than 1 in 3 patients have seizures despite treatment with AEDs (Schmidt & Gram, 1995). Treatment of refractory epilepsy will move to polytherapy by adding second-generation AEDs available after 1993 (e.g. felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, vigabatrin, zonisamide) to monotherapy regimens (adjunctive therapy). A literature review of systematic reviews reported that second-generation AEDs were effective as adjunctive therapy for refractory epilepsy as compared with placebo (Wilby et al., 2005). Also, a literature review of economic evaluations of second-generation AEDs showed that adjunctive therapy of refractory epilepsy with AEDs appears to be cost-effective (Simoens, 2010). Several factors inform the choice of the most appropriate treatment regimen in patients requiring adjunctive therapy. Of key importance is that adjunctive therapy for uncontrolled