title: 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.
authors.affiliation: Kork Epilepsy Centre, Kehl-Kork, Germany. Electronic address: BSteinhoff@epilepsiezentrum.de.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Steinhoff
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany. Electronic address: Klaus.Eckhardt@ucb.com.
authors.forename: Klaus
authors.initials: K
authors.lastname: Eckhardt
authors.affiliation: UCB Pharma, Raleigh, NC, USA. Electronic address: Pamela.Doty@ucb.com.
authors.forename: Pamela
authors.initials: P
authors.lastname: Doty
authors.affiliation: UCB Pharma, Brussels, Belgium. Electronic address: Marc.DeBacker@ucb.com.
authors.forename: Marc
authors.initials: M
authors.lastname: De Backer
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany. Electronic address: Marcus.Brunnert@ucb.com.
authors.forename: Marcus
authors.initials: M
authors.lastname: Brunnert
authors.affiliation: University Hospital Freiburg, Freiburg, Germany. Electronic address: Andreas.Schulze-Bonhage@uniklinik-freiburg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze-Bonhage
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000078334:Lacosamide; D000077287:Levetiracetam; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000077287:Levetiracetam; D000078334:Lacosamide; D010889:Piracetam
keywords: Adverse reactions; Cardiovascular system; Consumer product safety; Drug-related side effects; Postmarketing product surveillance; Psychiatry