Student Research Assistant Johns Hopkins University School of Medicine
Rationale: A large proportion of patients have frequent focal-onset seizures despite treatment with newer antiepileptic drugs (AEDs). We describe our experience managing AEDs, optimizing cenobamate doses and treatment outcomes for 49 patients treated at one center for up to 8 years. Methods: Forty-nine patients were enrolled from three regulatory trials for cenobamate at the Johns Hopkins Hospital to participate in a long-term follow up study. Patient had focal-onset seizures despite treatment with one to three AEDs and were 18 and older. Patients kept seizure diaries for the duration of the study, and these were monitored during trimonthly evaluations. The >50%, >75%, >90%, and 100% seizure responder rates were determined by comparing seizure frequencies from the most recent three-month evaluation period to baseline data. Patients with long-term seizure freedom during cenobamate treatment, defined as >6 months with no seizures, were identified following their most recent study visit. These trimonthly evaluations were also used to monitor patients’ AEDs. Concomitant AEDs were adjusted as necessary by an investigator, while cenobamate doses were only manipulated within the permitted range of 100 to 400 mg/day. Results: Of the 49 patients initially enrolled in the study, 12 (24%) discontinued treatment within two years. The median exposure to cenobamate across all trials was 5.6 years. Two patients had severe treatment-emergent adverse events requiring discontinuation—both had been seizure free: one had SUDEP after missing doses while moving; another had serious allergy with swelling, fever, erythema which resolved rapidly after stopping treatment. After three to eight years of treatment, 45% of patients had 75% seizure reduction, 29% had 90% reduction and 16% were seizure free. All focal seizure types responded and tonic clonic seizures ceased in eight of nine patients. Symptomatic etiologies did not reduce treatment responses. Increased dosage of cenobamate across the range 150 to 400 mg/day was significantly associated with higher responder rates (p=.0008). Patients often had doses of concomitant AEDs reduced when cenobamate was titrated. Conclusions: Patients with drug-resistant focal onset epilepsy had stable treatment responses during up to eight years of cenobamate treatment. Patients often tolerated high, effective doses of cenobamate by reducing other AEDs. High responder rates were unique in this highly treatment resistant group compared to their earlier treatment trials. Funding: Please list any funding that was received in support of this abstract.: The author(s) received no financial support for the research, authorship, and/or publication of this article.
