Rationale:
Eslicarbazepine acetate (ESL) is a once-daily, oral anti-seizure drug (ASD) 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 ASDs in patients with focal seizures, in a real-world setting. Pre-existing seizure burden was variable amongst patients, as demonstrated by the higher mean than median standardized seizure frequency (SSF) at baseline (Arm 1: 4.8 vs 2.0; Arm 2: 18.3 vs 2.4, respectively). In order to determine whether the baseline seizure burden influenced response to therapy, we analyzed efficacy outcomes according to baseline SSF quartile.
Method:
This was a multicenter, open-label, non-randomized Phase IV study of adjunctive ESL in patients aged ≥ 18 years with focal seizures in the USA and Canada (NCT03116828). In Arm 1, patients received ESL as first adjunctive therapy with LEV or LTG. In 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 SSF values > Q3 + 1.5*interquartile range (IQR) were identified as outliers. Patients were divided into quartiles according to baseline SSF, either including or excluding outliers. Efficacy endpoints included retention rate, change from baseline in SSF (seizures per 4 weeks), responder rate (proportion of patients with a ≥ 50% reduction from baseline in SSF), and seizure freedom rate.
Results:
In the efficacy analysis population, there were 44 patients in Arm 1 (ESL as 1st add-on) and 58 patients in Arm 2 (ESL as later add-on). When outliers were excluded, there were 40 patients in Arm 1 and 48 patients in Arm 2; all 14 outliers were in baseline SSF Q4. In Arm 1 Q4, retention rates were 81.8% including outliers and 85.7% excluding outliers; in Arm 2 Q4, retention rates were 64.3% and 80.0%, respectively. As efficacy outcomes were not markedly different when excluding outliers, we proceeded to analyze efficacy according to baseline SSF quartile without excluding outliers. Overall, there was no clear relationship between baseline SSF quartile and retention rate, median change from baseline in SSF, 50% responder rate, or seizure freedom rate, in Arm 1 or Arm 2 (Table 1). An exception was median change from baseline in SSF in Arm 2. The overall change from baseline in SSF was heavily skewed by one patient in Arm 2 Q1, whose SSF increased from 1 to 15 during the study; however, the patient did not discontinue treatment due to the increase.
Conclusion:
In this real-world open-label study, ESL was effective for the treatment of focal seizures across the range of patient baseline seizure frequencies.
Funding:
:Study funded by Sunovion Pharmaceuticals Inc.
FIGURES
Figure 1