Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral anti-seizure medication approved for the treatment of focal seizures. Here, we report a post-hoc analysis of data from a Phase IV study of ESL taken as a first adjunctive therapy with levetiracetam (LEV) or lamotrigine (LTG) monotherapy, or as later adjunctive therapy following current or prior use of 1–2 anti-seizure medications in patients with focal seizures, in a real-world setting. The objective of this analysis was to determine the time required to reach baseline seizure count, as an alternative way of assessing efficacy in patients with relatively low monthly seizure frequencies at baseline.

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 or prior use of adjunctive therapy. The trial comprised screening (1–2 weeks), titration (2 weeks), maintenance (24 weeks), and ESL taper/safety follow-up (4 weeks) periods. Baseline seizure count was determined using information from patient seizure diaries. Endpoints analyzed for the 24-week maintenance period were: time to reach individual total baseline seizure count and time to ESL discontinuation in the modified intent-to-treat population; and time to first report of treatment-emergent adverse events (TEAEs) and time to first report of a dizziness TEAE in the safety population. Kaplan–Meier curves, hazard ratios (HRs) and 95% confidence intervals (CIs) were generated for the time-to-event analysis.

Results: The time to reach individual baseline seizure count showed that patients in Arm 2 reached their baseline seizure count earlier than patients in Arm 1 (HR: 2.131; 95% CI: 1.262–3.598; p=0.005) (Figure 1). There was no difference in time to baseline seizure count in either arm according to concomitant LEV or LTG. Patients in Arm 1 had a longer time to ESL discontinuation than patients in Arm 2 (HR: 2.343; 95% CI: 1.037–5.293; p=0.041), but there was no difference within arms (concomitant LEV vs LTG). Analysis of the time to first report of a TEAE showed no significant difference between arms (HR: 1.218; 95% CI: 0.774–1.917; p=0.39) (Figure 2); however, in Arm 1, patients receiving concomitant LEV reported TEAEs earlier than those receiving LTG (HR: 2.379; 95% CI: 1.166–4.852; p=0.017). Reports of the time to TEAE dizziness did not differ between arms (HR: 1.406; 95% CI: 0.590–3.354; p=0.44).

Conclusions: The time to reach individual baseline seizure count was longer in patients with focal seizures receiving ESL as a first versus later adjunctive therapy. In addition, patients who received ESL as a first adjunctive therapy had a longer time to ESL discontinuation. There were no differences between patients receiving ESL as a first or later adjunctive therapy with regard to TEAEs.

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