Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral anti-seizure medication (ASM) approved for the treatment of focal seizures. In a real-world, Phase IV study of ESL as a first adjunctive therapy with levetiracetam (LEV) or lamotrigine (LTG) monotherapy (Arm 1), or as a later adjunctive therapy following current/prior use of 1–2 ASMs (Arm 2) in patients with focal seizures, retention rates were 81.8% and 63.8% (Hixson J, et al. Epilepsy Res 2021;171:106561). Median change from baseline in standardized seizure frequency (SSF) was –72.8% in Arm 1 and –68.6% in patients receiving LEV in Arm 2 (Hixson J, et al. Epilepsy Res 2021;171:106561). As dosing was at the discretion of the investigator based on patient needs, doses ranged between 800 and 1600 mg, with a single dose reduction allowed to improve tolerability. The objective of this post-hoc analysis was to determine how varying ESL doses affected efficacy endpoints in the trial.

Methods: This was a multicenter, open-label, non-randomized Phase IV study of adjunctive ESL in patients aged ≥ 18 years with focal seizures in the US and Canada (NCT03116828). Arm 1: patients received ESL as first adjunctive therapy with LEV or LTG; Arm 2: patients received ESL as a later adjunctive therapy, following current/prior use of adjunctive therapy. Trial periods were screening (1–2 weeks), titration (2 weeks), maintenance (24 weeks), and ESL taper/safety follow-up (4 weeks). The endpoint analyzed using the modified intent-to-treat population was percent change from baseline in SSF according to modal or maximum ESL dose. The proportions of patients completing the 24-week maintenance phase in the safety population by modal and maximum doses of ESL were also determined. Arm 1 vs Arm 2, and LEV vs LTG within Arms 1 and 2, were compared.

Results: Stratification of median SSF at baseline and median change from baseline in SSF by modal or maximum ESL dose (Tables 1 and 2) showed that the previously reported 73% reduction in SSF in Arm 1 was mostly attributable to receipt of the modal/maximum ESL dose of 800 mg. Similarly, a modal/maximum ESL dose of 800 mg was mostly responsible for the previously reported 69% reduction in SSF in Arm 2 patients receiving LEV. All patients in Arm 1 who were receiving a modal/maximum dose of 1600 mg were receiving concomitant LEV. A modal/maximum ESL dose of 800 mg was also mostly responsible for the previously reported retention rates seen in Arm 1 and Arm 2 in the overall analysis. Of the patients in Arm 1 and Arm 2 receiving a modal dose of 800 mg, 30/33 (90.9%) and 27/40 (67.5%) completed 24 weeks. These proportions were similar to those seen with a maximum dose of 800 mg (23/26 [88.5%] and 21/31 [67.7%]).

Conclusions: Stratification of the data from the Phase IV study of adjunctive ESL showed that retention rates and reduction in SSF at 24 weeks is mostly driven by patients receiving the lowest allowed ESL maintenance dose of 800 mg, regardless of whether ESL was taken as a first or as a later adjunctive therapy.

Funding: Please list any funding that was received in support of this abstract.: Study funded by Sunovion Pharmaceuticals Inc.