Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a novel once-daily (QD) anticonvulsant, extensively converted to eslicarbazepine after oral administration, which blocks voltage-gated sodium- and calcium-channels. Although ESL and carbamazepine (CBZ) do not share any common metabolites they are chemically related. Furthermore, CBZ is one of the most frequently used antiepileptic drugs (AEDs). It is important to assess the effect of ESL in patients not achieving complete seizure control under treatment with CBZ. This post-hoc analysis evaluated the efficacy and tolerability of adjunctive ESL therapy in adult patients with partial-onset seizures (POS) refractory to lower and higher dosages of CBZ. Methods: Data from two phase III multicentre, double-blind, randomized, placebo-controlled studies in adult patients with ≥4 partial-onset seizures per 4 weeks despite treatment with 1-3 AEDs was pooled and analysed. ESL was administered at QD doses of 400 mg, 800 mg and 1200 mg. Efficacy and tolerability was evaluated in patients not co-treated with CBZ (noCBZ) and patients co-treated with CBZ ≤ 800 mg daily (CBZ≤ 800) or with CBZ > 800 mg daily (CBZ>800), as part of their baseline AEDs. Results: Safety population comprised 797 patients (noCBZ, n=328; CBZ≤ 800, n=193; CBZ>800, n=276) and intention-to treat population included 752 patients (noCBZ, n=314; CBZ≤ 800, n=183; CBZ>800, n=255). Compared with placebo seizure frequency over the 12-week maintenance period (primary end point) was significantly reduced with ESL 800 mg and 1200 mg in all three patient subgroups (p≤0.05) (table 1); ESL 400 mg was not significantly superior to placebo. Responder rate (≥50% reduction in seizure frequency) was: noCBZ group = 23% with placebo, 40% with ESL 800 mg and 39% with ESL 1200 mg; CBZ≤800 group = 18% with placebo, 37% with ESL 800 mg and 50% with ESL 1200 mg; CBZ>800 group = 16% with placebo, 31% with ESL 800 mg and 44% with ESL 1200 mg. Median relative reduction in seizure frequency was: noCBZ group = -13% with placebo, -39% with ESL 800 mg and -33% with ESL 1200 mg; CBZ≤800 group = -14% with placebo, -34% with ESL 800 mg and -50% with ESL 1200 mg; CBZ>800 group = -9% with placebo, -29% with ESL 800 mg and -38% with ESL 1200 mg. Incidence of treatment-emergent adverse events (TEAEs) was higher in CBZ>800 group (54% with placebo, 74% with ESL 800 mg and 78% with ESL 1200 mg) than in CBZ≤800 group (49% with placebo, 71% with ESL 800 mg and 71% with ESL 1200 mg) and noCBZ group (46% with placebo, 57% with ESL 800 mg and 64% with ESL 1200 mg) (table 2). Conclusions: In this post-hoc analysis, the efficacy of adjunctive ESL treatment was independent from concomitant CBZ therapy. Patients with POS refractory to CBZ dosages higher than 800 mg daily achieved a significant improvement in seizure control with adjunctive once-daily ESL 800 mg and 1200 mg. The incidence of TEAEs was higher in patients treated concomitantly with CBZ, especially if CBZ dosage was higher than 800 mg daily.