Abstracts

Rationale: In patients with refractory generalized seizure types, the ultimate goal of achieving seizure-free status is often elusive. Therefore, it is important to investigate antiepileptic drugs (AEDs) with novel mechanisms of action to improve outcomes for patients with generalized seizure types. PER is a once-daily oral AED for partial-onset seizures and primary generalized tonic-clonic seizures. Adjunctive PER (=12 mg/day) has demonstrated efficacy and tolerability for partial-onset seizures in 3 Phase III randomized, double-blind, placebo-controlled studies. Patients completing 1 of these studies could enter the OLEx Study 307 (NCT00735397). Our post hoc analysis investigated SG seizure-free status rates achieved during adjunctive treatment with PER (=12 mg/day) in patients aged =12 years with SG seizures from Study 307 to determine if responses from the double-blind studies were maintained in the OLEx. Methods: Study 307 methodology has been published (Krauss GL et al. Epilepsia 2018;59:866–876). This post hoc analysis included patients with SG seizures who participated in Study 307 and achieved SG seizure-free status during either the preceding double-blind studies or the PER Treatment Duration (defined as the OLEx Phase for patients randomized to placebo during the double-blind studies, or the Double-blind and OLEx Phases for patients randomized to PER during the double-blind studies). SG seizure-free status rates were assessed at 6, 12, 18, 24, 30, 36, 42, and 48 months in patients who achieved SG seizure-free status during the double-blind studies. Patients were also assessed for SG seizure freedom for =6, =12, =18, =24, =30, =36, =42, and =48 months at any time during the PER Treatment Duration. Results: Eighty patients who received PER during the double-blind studies achieved SG seizure-free status. Of these, 74/78 (94.9%), 57/78 (73.1%), 42/78 (53.8%), and 22/63 (34.9%) patients remained SG seizure free for 6, 12, 24, and 36 months, respectively (Table 1; the denominator decreases over time due to patients dropping out of the study even if seizure free).For patients treated with PER during the PER Treatment Duration, SG seizure freedom was achieved in 202/453 (44.6%), 145/453 (32.0%), 96/448 (21.4%), and 48/345 (13.9%) patients for =6, =12, =24, and =36 months, respectively. SG seizure-free status rates were similar irrespective of prior treatment during the double-blind studies. Conclusions: Of 80 patients who received adjunctive PER (=12 mg/day) and achieved SG seizure-free status during the double-blind studies, 42/78 (53.8%) and 22/63 (34.9%) remained SG seizure free for 24 and 36 months, respectively. For the PER Treatment Duration, SG seizure free status rates were similar irrespective of prior treatment during the double-blind studies. These data are encouraging given the refractory nature of generalized seizure types and suggest adjunctive PER may offer a long-term treatment option for patients with SG seizures. Funding: Eisai Inc.