Time to sustained responder status in patients with focal seizures treated with adjunctive eslicarbazepine acetate

Abstract

Rapid and sustained clinical responses are critical in improving long-term outcomes in epilepsy. While a 50 % reduction from baseline in standardized seizure frequency (SSF) is often cited as a measure of clinically meaningful efficacy, sustained response (SR) is an alternative method that allows the assessment of onset and durability of the response. Time to sustained response in SSF of ≥ 50 %, ≥ 75 %, ≥ 90 %, and 100 % was assessed for pooled data from 3 similar randomized clinical trials of adjunctive eslicarbazepine acetate (ESL). Patients with focal seizures on stable doses of 1–2 antiseizure medications were randomized to placebo, ESL 800 mg/day, or ESL 1200 mg/day. SR50, SR75, SR90, and SR100 were defined as a ≥ 50 %, ≥ 75 %, ≥ 90 %, and 100 % reduction, respectively, in SSF compared to baseline occurring anytime during the 12-week maintenance period, sustained through the end of the maintenance period. Safety signals were assessed for patients with SR50 onset within the first 2 weeks of the maintenance period (early responders) and any point following the first 2 weeks (later responders). A total of 1221 patients were included in this analysis. SR50 was achieved as early as Day 1 (placebo, 4.7 %; ESL 800 mg/day, 8.8 %; ESL 1200 mg/day, 10.4 %). After 84 days, SR50 was achieved by 32.1 % of the placebo group, 46.9 % of the ESL 800 mg/day group (p = 0.0002 vs placebo), and 53.7 % of the ESL 1200 mg/day group (p < 0.0001 vs placebo). Both ESL groups demonstrated earlier SR50 onset compared with placebo (p < 0.0001). Time to SR50 onset was not statistically different between the 800 and 1200 mg/day ESL dose groups. SR75 (p = 0.0001), SR90 (p = 0.0019), and SR100 (p = 0.0014) were achieved significantly earlier in the ESL 1200 mg/day groups vs placebo. SR75 was achieved significantly earlier in the ESL 800 mg/day group vs placebo (p = 0.0188), while achievements of SR90 (p = 0.0525) and SR100 (p = 0.0540) trended toward earlier occurrence. A greater proportion of patients in the ESL groups compared to the placebo group achieved an SR50 during the maintenance period, and those patients in the ESL groups also achieved SR50 and SR75 sooner than placebo treated patients. Additionally, patients treated with the higher ESL dose achieved SR90 and SR100 sooner than those treated with placebo.