Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug, approved in the US and EU as adjunctive treatment of partial-onset seizures (POS). After oral administration, ESL is rapidly metabolized to eslicarbazepine (Bialer and Soares-da-Silva, Epilepsia 2012;53:935-46), which is thought to act primarily by stabilizing the inactivated state of voltage-gated sodium channels (Hebeisen et al. Epilepsia 2011;52[Suppl 6]:257-8). A pooled analysis of data from three randomized, double-blind, placebo (PBO)-controlled studies (2093-301, -302, and -304) demonstrated that ESL is associated with improvements in seizure control (Biton et al. Epilepsy Curr 2014;14[Suppl. 1]:209-10). The database has now been analyzed for evidence of exacerbation of seizures associated with use of adjunctive ESL for POS. Methods: Seizure diary data were evaluated to identify the proportion of trial subjects with an increase in POS frequency from baseline (any magnitude of increase, and ≥25% increase). Adverse event (AE) reports were tabulated for the maintenance period and for the post-treatment period, in order to identify subjects who reported seizures (any type) during treatment with ESL. Results: During the maintenance period, according to diary counts, 19.7% of subjects taking PBO had ≥25% increase in seizure frequency, compared with 12.4%, 12.0%, and 14.2% of those taking ESL 400mg, 800mg, and 1200mg QD, respectively (p<0.05 versus placebo for all ESL dose groups; see Figure 1). Increase in seizure frequency (of any magnitude) occurred in 32.8% of the PBO group, versus 23.8%, 24.3%, and 24.1% of the ESL 400mg, 800mg, and 1200mg groups, respectively. Seizures were reported as AEs (any related term) during the maintenance period in 3.2% of the PBO group, vs 2.1%, 2.6%, and 1.9% of the ESL groups, respectively (2.2% of all patients taking ESL), and during the post-treatment period, in none of the PBO group, compared with 4.3%, 1.1%, and 1.2% of subjects who previously had been taking ESL 400, 800, and 1200mg, respectively (2.2% of all those previously on ESL). Conclusions: Compared with PBO, there was a trend towards fewer increases in seizures (as measured by seizure diaries, or reports of seizures as AEs) during ESL maintenance treatment. Reporting of seizures as AEs was uncommon but more frequent after discontinuation of ESL than after discontinuation of PBO. Based on the current analysis, there is no evidence to suggest that ESL leads to exacerbation of POS.