Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED) for focal seizures. Here, we report efficacy outcomes from a recently completed Phase 4 study of ESL taken as a first adjunctive therapy with levetiracetam (LEV) or lamotrigine (LTG) monotherapy, or as later adjunctive therapy in treatment-resistant patients with focal seizures, in a real-world setting. This is the first time that adjunctive ESL has been evaluated at an early stage in the treatment trajectory in North American patients. Methods: A multicenter, open-label, non-randomized Phase 4 study of adjunctive ESL in patients aged ≥18 years with focal seizures in the USA and Canada (NCT03116828). Patients with prior exposure to ESL or currently using oxcarbazepine were excluded. Arm 1: ESL as first adjunctive therapy with LEV (n = 28) or LTG (n = 14) in patients with inadequate response to treatment. Arm 2: ESL as a later adjunctive therapy, following prior use of 1–2 AEDs in patients who required an additional therapeutic option (n = 59). The trial comprised screening (1–2 weeks), titration (2 weeks), maintenance (24 weeks), and ESL taper/safety follow-up (4 weeks) periods. Results: Overall, 102 patients entered the study (Arm 1: n = 43; Arm 2: n = 59); 69.8% of patients in Arm 1 and 55.9% of patients in Arm 2 completed the 24-week maintenance period. The majority of patients had an epilepsy duration <20 years (Arm 1: 83.7%; Arm 2: 62.7%). In Arm 1, 65.1% of patients were taking LEV and 32.6% were taking LTG. In Arm 2, 37.3% of patients were taking one baseline AED and 62.7% were taking >1 baseline AED. Complex partial (focal unaware) seizures were the most severe seizure type during baseline in the majority of patients (Arm 1: 58.1%; Arm 2: 70.7%). At baseline, median standardized seizure frequency (SSF: seizures per 28 days) was 2.0 in Arm 1 and 2.4 in Arm 2. At 24 weeks, median reductions in SSF were higher in Arm 1 (74.0%) than in Arm 2 (23.7%; Figure 1A). Responder rates (proportion of patients with ≥50% reduction in SSF) were also higher in Arm 1 (63.2%) than in Arm 2 (37.7%; Figure 1B). A total of 26.3% of patients in Arm 1 remained seizure free during the 24-week maintenance period, compared with 9.4% of patients in Arm 2 (Figure 1C). Conclusions: In this real-world open-label study, ESL was effective for treatment of focal seizures. Seizure improvements were greater when ESL was taken as a first adjunctive therapy with LEV or LTG monotherapy, compared with when taken as a later adjunctive therapy. Funding: Study funded by Sunovion Pharmaceuticals Inc.