TY - JOUR
T1 - Efficacy of cenobamate for uncontrolled focal seizures in patients with previous epilepsy-related surgery
T2 - Post hoc analysis of a phase 3, multicenter, open-label study
AU - Abou-Khalil, Bassel
AU - Aboumatar, Sami
AU - Klein, Pavel
AU - Krauss, Gregory L.
AU - Sperling, Michael R.
AU - Rosenfeld, William E.
N1 - Funding Information:
This study and post hoc analysis were funded by SK Life Science, Inc . The study funder consulted with advisors and study investigators on the design of the original study and post hoc analysis, provided financial and material support for the study, and, with the assistance of study investigators, monitored the conduct of the study, collected data from the investigative centers, and analyzed the data. The corresponding author (BAK) had full access to all study data and had final responsibility for the decision to submit for publication. All authors approved the final version of the manuscript for publication.
Publisher Copyright:
© 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - Objective: This post hoc analysis of 10 US study sites from a long-term open-label phase 3 study of adjunctive cenobamate evaluated the efficacy of cenobamate in patients with prior epilepsy-related surgery. Methods: Patients with uncontrolled focal seizures despite taking stable doses of 1–3 concomitant antiseizure medications (ASMs) received increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals over 12 weeks (target dose, 200 mg/day). Further increases up to 400 mg/day using biweekly 50-mg/day increments were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until the last clinic visit on or after September 1, 2019. Results: Of the 240 eligible patients, 85 had prior epilepsy-related surgery and 155 were nonsurgical patients. Baseline focal seizure frequency per 28 days was numerically higher among prior surgery (mean=25.9/median=4.1/range=0.3–562.3) versus nonsurgical (mean=13.8/median=2.4/range=0.2–534.2) patients. Among all patients, 100 % seizure reduction ≥ 12 months at any consecutive month interval occurred in 30.6 % (26/85) prior surgery and 39.4 % (61/155; p > 0.05) nonsurgical patients (cenobamate treatment median duration=32.9 months). Among the 177 patients still receiving cenobamate at the data cutoff, 29.2 % (19/65) of prior surgery and 36.6 % (41/112; p > 0.05) of nonsurgical patients had 100 % seizure reduction ≥ 12 months at the data cutoff. Cenobamate was well tolerated. Conclusions: This post hoc analysis supports the efficacy of cenobamate in patients with refractory focal seizures despite prior surgery. These findings suggest cenobamate may be considered early in the treatment regimen, including, in some patients, before surgery is considered.
AB - Objective: This post hoc analysis of 10 US study sites from a long-term open-label phase 3 study of adjunctive cenobamate evaluated the efficacy of cenobamate in patients with prior epilepsy-related surgery. Methods: Patients with uncontrolled focal seizures despite taking stable doses of 1–3 concomitant antiseizure medications (ASMs) received increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals over 12 weeks (target dose, 200 mg/day). Further increases up to 400 mg/day using biweekly 50-mg/day increments were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until the last clinic visit on or after September 1, 2019. Results: Of the 240 eligible patients, 85 had prior epilepsy-related surgery and 155 were nonsurgical patients. Baseline focal seizure frequency per 28 days was numerically higher among prior surgery (mean=25.9/median=4.1/range=0.3–562.3) versus nonsurgical (mean=13.8/median=2.4/range=0.2–534.2) patients. Among all patients, 100 % seizure reduction ≥ 12 months at any consecutive month interval occurred in 30.6 % (26/85) prior surgery and 39.4 % (61/155; p > 0.05) nonsurgical patients (cenobamate treatment median duration=32.9 months). Among the 177 patients still receiving cenobamate at the data cutoff, 29.2 % (19/65) of prior surgery and 36.6 % (41/112; p > 0.05) of nonsurgical patients had 100 % seizure reduction ≥ 12 months at the data cutoff. Cenobamate was well tolerated. Conclusions: This post hoc analysis supports the efficacy of cenobamate in patients with refractory focal seizures despite prior surgery. These findings suggest cenobamate may be considered early in the treatment regimen, including, in some patients, before surgery is considered.
KW - Antiseizure medication
KW - Clinical trial
KW - Seizure freedom
KW - Seizure-free
KW - Treatment-refractory
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U2 - 10.1016/j.eplepsyres.2022.106952
DO - 10.1016/j.eplepsyres.2022.106952
M3 - Article
C2 - 35671632
AN - SCOPUS:85131383574
SN - 0920-1211
VL - 184
JO - Journal of Epilepsy
JF - Journal of Epilepsy
M1 - 106952
ER -