Abstracts

Rationale: An estimated 3.4 million people in the United States (US) are impacted by epilepsy, a chronic neurological condition characterized by spontaneous, recurrent seizures. Up to 60% of all cases of epilepsy involve focal seizures (FS). Eslicarbazepine acetate (ESL) is indicated for the treatment of patients with FS aged ≥4 years. Recently, a Phase 4 trial (ClinicalTrials.gov NCT03116828) was conducted to evaluate the effectiveness of once-daily ESL as the first adjunctive therapy to levetiracetam (LEV) or lamotrigine (LTG) or as later adjunctive therapy in patients with FS. The objective of this analysis was to report the effect of treatment with ESL, both as first adjunctive or later adjunctive therapy, on patients’ health-related quality of life (HRQoL). Methods: The Phase 4 trial was a multicenter, open-label, nonrandomized study in patients aged ≥18 years with FS. The 2 treatment arms were ESL as first adjunctive therapy to LEV or LTG in patients with inadequate response (Arm 1) or following use of 1–2 AEDs (Arm 2). The trial included a screening phase (1-2 weeks), titration phase (2 weeks), maintenance phase (24 weeks), and an ESL taper/safety follow-up (4 weeks) phase. HRQoL was measured using the Quality of Life in Epilepsy (QOLIE-31) patient-reported survey instrument at baseline and weeks 11 and 27; higher values indicate better HRQoL. QOLIE-31 contains 7 multi-item subscales; the seizure worry (SW) and social functioning (SF) subscales quantify patients’ perception of seizure reduction and ability to carry out activities of daily living. Results: 102 patients were enrolled in this study: 43 in Arm 1 and 59 in Arm 2. Mean age was 42.5 years (Arm 1: 43.6 years; Arm 2: 41.7 years), and 58.8% were female (Arm 1: 53.5%; Arm 2: 62.7%). The duration of epilepsy was <20 years in 83.7% of patients in Arm 1 and 62.7% of patients in Arm 2. 62.7% of patients in Arm 2 had >1 concomitant AEDs. Baseline mean (standard deviation [SD]) QOLIE-31 overall score was 69.58 (13.68) in Arm 1 and 60.66 (18.63) in Arm 2. Mean QOLIE-31 overall scores (SD) in Arm 1 were 70.47 (17.57) at week 11 and 70.49 (18.10) at week 27. Mean QOLIE-31 overall scores (SD) in Arm 2 were 61.55 (18.73) at week 11 and 60.46 (19.95) at week 27. The greatest improvements were observed for the SW and SF subscales (Figure 1). Scores (SD) for SW at baseline and at weeks 11 and 27 were 53.91 (26.48), 59.36 (27.72), and 62.76 (27.94) in Arm 1, and 46.31 (29.82), 53.07 (29.64), and 49.01 (30.52) in Arm 2. Scores (SD) for SF at baseline and at weeks 11 and 27 were 69.21 (24.60), 71.90 (25.04), and 78.21 (23.55) for Arm 1, and 61.36 (24.63), 61.39 (24.36), and 61.97 (27.91) for Arm 2. The changes in scores observed from baseline to week 27 in Arm 1 on the domains of SW and SF exceeded clinically meaningful thresholds of 7.42 and 3.95, respectively. Conclusions: In this Phase 4 study, once-daily ESL was associated with numerical improvements in HRQoL, as measured by the QOLIE-31, in patients with FS when given as first and later adjunctive AED. The improvements in QOLIE-31 scores from baseline to week 27 on patient-reported domains of SW and SF were numerically greater in the treatment arm where ESL was taken as a first adjunctive therapy with LEV or LTG monotherapy, compared with when taken as a later adjunctive therapy. Funding: Study funding provided by Sunovion Pharmaceuticals Inc.