Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED), approved in the EU, US and Canada as adjunctive treatment of partial-onset seizures (POS). An important consideration for clinicians managing patients with combinations of AEDs is the frequency of adverse events (AEs) seen with specific combinations, particularly agents thought to have similar mechanism(s) of action. This post-hoc analysis evaluated the impact of lamotrigine (LTG) use on the incidence of treatment emergent AEs (TEAEs) during adjunctive ESL treatment. Both ESL and LTG block voltage-gated sodium channels (VGSC), which may contribute to their anticonvulsant effects. The analysis therefore excluded patients taking other AEDs believed to act predominantly via VGSC inhibition, i.e., carbamazepine (CBZ) and phenytoin (PHT).Methods: Data from three double-blind Phase III studies of adjunctive ESL (BIA-2093-301, -302 and -304) were pooled. Patients with ≥4 POS/month, taking 1–3 AEDs received placebo (PBO) or ESL 400 mg (studies -301 and -302 only), 800 mg, or 1200 mg QD. Patients continued to receive stable doses of baseline AEDs; those taking CBZ or PHT at baseline were excluded from this analysis. Data were analyzed for patients who received at least one dose of ESL. TEAE incidences were calculated for patients taking or not taking LTG at baseline. PBO-adjusted incidences were calculated as [incidence in the ESL (800 mg or 1200 mg) groups, minus incidence in the PBO group].Results: After excluding patients taking CBZ or PHT, a total of 248 patients were taking LTG (+LTG groups; PBO, 81; ESL, 167), and 361 were not taking LTG at baseline (-LTG groups; PBO, 109; ESL, 252). Compared with the -LTG group, a larger proportion of the +LTG group was taking ≥2 baseline AEDs, but a smaller proportion was taking valproic acid or levetiracetam (Table 1). A similar percentage of ESL-treated patients discontinued due to AEs in the ‑LTG (10.3%) and +LTG (10.2%) groups. The overall incidence of TEAEs was similar in the -LTG (PBO, 58%; ESL, 68%) and +LTG (PBO, 57%; ESL, 73%) groups. Among patients taking ESL 1200 mg QD, the total PBO-adjusted incidence of TEAEs was 8% higher in the +LTG subgroup than the -LTG subgroup. Across ESL doses, the incidences of the most frequently occurring TEAEs were similar between the ‑LTG and +LTG subgroups (Figure 1). Among patients taking ESL, the incidence of rash was not greater in the +LTG subgroup (1.2%, n=2) than the -LTG subgroup (5.6%, n=14). The incidence of hyponatremia in ESL-treated patients was low (-LTG, 1.6% [n=4]; +LTG, 2.4% [n=4]).Conclusions: Approximately a quarter of patients enrolled in the Phase III studies were taking LTG. Among patients not taking baseline CBZ or PHT, the incidence of TEAEs did not appear to be markedly higher in those who were taking LTG compared to those who were not. Studies sponsored by Sunovion Pharmaceuticals Inc.