Abstracts

Rationale: Two phase III studies (093-045 and -046) have shown that switching from adjunctive antiepileptic drug (AED) therapy to eslicarbazepine acetate (ESL) monotherapy is effective and well tolerated in patients with partial-onset seizures (Pazdera et al, Epilepsy Curr 2014;14[Suppl.1]:108; Sperling et al, Epilepsy Curr 2014;14[Suppl.1]:431−2). ESL is not approved for treatment of seizures as monotherapy. Here we present an analysis of data from the open-label extension (OLE) of these studies, to assess long-term retention, efficacy, and safety of ESL. Methods: Studies -045 and -046 were 18-wk, randomized, double-blind, conversion-to-monotherapy studies which evaluated ESL 1200 and 1600mg once-daily (QD), compared with a historical control. Patients who completed, discontinued, or exited these studies after completing ≥3 wks of ESL treatment were eligible to receive open-label ESL 800-2400mg QD. Up to two additional AEDs were allowed as needed. Patient evaluations (laboratory tests, and analysis of seizure diaries and treatment-emergent adverse event [TEAE] records) were conducted at 3-monthly intervals. The study is ongoing; data cut-off for this analysis was May 31, 2013. Results: A total of 274 patients entered the OLE study: the median age was 37.0 years; 83.6% were Caucasian; 36.1% had epilepsy for ≥20 years; and 69.7% and 30.3% had received one and two prior AEDs, respectively. At data cut-off, 134 patients had completed 1 year of treatment and 73 patients were ongoing in the 1-year period; 125 patients were ongoing in the post 1-year period. The mean daily dose of ESL was 1603mg and mean overall exposure was 395 days. The most frequently reported TEAEs were headache and dizziness. Serious TEAEs were reported for 38 patients (13.9%); 15 patients (5.5%) discontinued due to TEAEs, and three patients (1.1%) died (one death was post-treatment). Adverse events of special interest were anemia, ↑alanine aminotransferase (ALT), ↑aspartate aminotransferase (AST), rash, AV block (ECG) (n=1 each), AST/ALT ≥3x ULN, and CSSRS suicidality (n=2 each). One patient accidentally took double his regular 2400mg QD dose; he reported nausea, dizziness, and double vision, and was reported to have recovered. Median reduction from baseline in standardized seizure frequency was 67.3%, with 64.4% of patients having reductions ≥50%. Figure 1 shows the median seizure reduction over time. ESL monotherapy was maintained in 66.1% of patients (i.e. no other AEDs were added). Conclusions: The safety results from this long-term study are consistent with the ESL safety profile reported in the adjunctive therapy trials (Rogin et al, Epilepsy Curr 2014;14[Suppl.1]:209). The improvements in seizure control achieved during studies -045 and -046 were maintained during the OLE phase. Approximately two-thirds of patients (66.1%) continued with ESL as monotherapy. These data suggest good long-term efficacy and tolerability with ESL, in a significant proportion of patients.