A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

Abstract

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were reported by four patients who added lacosamide (two cases of depression, two of suicide attempt) and one who added another AED (depression). Seven deaths occurred, all of which were considered unrelated/unlikely related to study medication. This thorough evaluation revealed a low incidence of predefined CV- and psychiatric-related TEAEs in patients taking adjunctive AED therapy according to standard medical practice. No specific safety concerns related to adjunctive lacosamide therapy were noted.

Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures

“…Following approval, there was an open-label, multicenter, non-interventional study conducted using a physician-driven decision to prescribe adjunctive treatment with lacosamide (n = 511) or another marketed AED therapy (n = 493) to patients with POS (23). The primary end point of the study was frequency of predefined cardiovascular TEAEs.…”

The efficacy of lacosamide as monotherapy and adjunctive therapy in focal epilepsy and its use in status epilepticus: clinical trial evidence and experience

“…A multitude of clinical trials with a prospective or descriptive study design and a total number of more than 1500 enrolled patients showed a >50% reduction in seizure frequency in 23-48.2% of patients [Wehner et al 2009;Garcia-Morales et al 2011;Stephen et al 2011;Husain et al 2012;Miro et al 2013;Novy et al 2013;Verrotti et al 2013;Villanueva et al 2013;Legros et al 2014;Borzi et al 2016;Lang et al 2016]. Seizure freedom under adjunctive therapy with LCM of up to 33% and a reduction of seizure frequency >90% in approximately 26% has been shown [Harden et al 2012;Steinhoff et al 2016]. In addition, several retrospective, descriptive or comparative trials confirmed these results, reporting a reduction in seizure frequency of >50% in up to 69% and an overall seizure freedom of up to 33% under treatment with LCM [Flores et al 2012;Harden et al 2012;Kamel et al 2013;Villanueva et al 2013].…”

“…In summary, the most common reported adverse effects (AEs) in post-marketing studies were similar to those reported in the RCTs. These included sedation, somnolence, fatigue, dizziness, nausea, unsteadiness, ataxia, headache and double vision [Flores et al 2012;Husain et al 2012;Kamel et al 2013;Novy et al 2013;Verrotti et al 2013;Villanueva et al 2013;Steinhoff et al 2016]. For details on common AEs, please refer to Table 4.…”

Lacosamide in status epilepticus: Systematic review of current evidence

“…11,12 Clinical efficacy was shown in five doubleblind randomized controlled trials, 8,[13][14][15][16] and further safety and tolerability data were generated in extension [17][18][19] and postmarketing studies. 20,21 Due to its intravenous formulation that is bioequivalent with oral preparations and overall good tolerability of LCM, [22][23][24] this anticonvulsant was used as a second-line or third-line therapy in SE. H€ ofler and Trinka described in detail the first evidence on the use of LCM in SE between 2009 and 2012.…”