The effectiveness of Cenobamate in patients previously treated with Vagus Nerve Stimulation for drug resistant epilepsy

Abstract

Background: Vagus Nerve Stimulation (VNS) is an efficacious neuromodulatory treatment for patients with drug resistant epilepsy (DRE). In many VNS treated patients, seizures are not fully controlled. These patients often represent a highly refractory group in whom novel anti-seizure medication (ASM) may be tried. This study evaluates the effectiveness of Cenobamate (CNB) in patients previously treated with VNS. Methods: The medication history of all patients treated with VNS at Ghent University Hospital and HUB-Hopital Erasme Brussels between 1995 and 2024 was reviewed. In patients who received an add-on treatment with CNB after at least 12 months of VNS therapy, mean monthly seizure frequency before VNS, after VNS, and after CNB was assessed. Results: 54/620 patients treated with VNS between March 1995 and November 2023 were treated with CNB after a median VNS treatment time of 9 years. With VNS, 13/52 (25%) had a seizure frequency reduction of ≥50%. Side-effects were mild and stimulation-related. After add-on of CNB (median daily dosage of 200mg) for a median follow-up of 10 months, 24/54 (44.4%) became responders. Of these patients, 6 (11.1% from total cohort) reported seizure freedom for a median duration of 26 weeks. Almost half (46.2%) of the VNS non-responders became CNB responder. The median number of concomitant ASM was 3. In 20/54 (37%), the number of ASM was reduced. 7/54 (13%) stopped CNB because of side-effects. Fatigue was the most prevalent side effect in 23/54 patients (42.6%). Conclusion: In DRE patients treated with VNS therapy who could benefit from further improvement in seizure control, add-on treatment with CNB is useful. This most recently marketed ASM leads to a significant improvement in seizure frequency in more than 40% of the patients.