Seizure Control After Focal Epilepsy Diagnosis Remains a Clinical Difficulty

Most patients with newly diagnosed focal epilepsy face a high risk for seizure recurrence in the first year, with many requiring multiple treatment trials before achieving seizure freedom. These study results were published in JAMA Neurology.

Predicting response to antiseizure medications (ASMs) among patients with newly diagnosed focal epilepsy remains challenging. The Human Epilepsy Project (ClinicalTrials.gov Identifier: NCT02126774) was a prospective cohort study conducted at 34 epilepsy centers in the United States, Australia, and Europe. Between 2012 and 2019, a total of 448 patients aged 12 to 60 years with newly diagnosed focal epilepsy were enrolled and followed through 2020.

The primary outcome was seizure freedom, defined as no seizures for 12 months or a tripling of the longest pretreatment seizure-free interval. Treatment response was categorized as sensitive (seizure freedom after 1 or 2 ASM trials), resistant (failure of 2 or more ASM trials), or indeterminate (not meeting criteria for either group).

The first year following treatment remains a high-risk period for recurrent seizures, and most will have their first ASM fail.

The patients were a median age of 29 (IQR, 18-40) years at seizure onset. In addition, 16.1% were younger than 18 years old, 59.6% were women or girls, 80.8% were White, and 21.0% had more than 1 seizure per week prior to ASM initiation.

During a median follow-up of 3.13 (IQR, 2.33-3.55) years, 59.6% of patients achieved at least 1 seizure-free period. Among patients who achieved seizure freedom, 83.5% did not relapse.

A total of 54.7% of patients were classified as sensitive to treatment, 22.8% as treatment resistant, and 22.5% as indeterminate. Among the sensitive group, 89.3% achieved seizure freedom with monotherapy, 49.4% of whom achieved seizure freedom with their first ASM. Among the resistant group, 20.6% achieved seizure freedom with their third ASM.

Classification as treatment sensitive was more likely among patients with infrequent seizures (relative risk [RR], 1.36; 95% CI, 1.10-1.69; P =.004) and a history of cardiovascular disorder (RR, 1.16; 95% CI, 1.00-1.35; P =.046), and less likely among patients with a history of psychological disorder (RR, 0.74; 95% CI, 0.61-0.90; P =.003).

Most (63%) participants had ongoing or worsening seizures during the first year of treatment. The median time to first seizure-free period was 12.1 (95% CI, 9.7-16.1) months. Among patients who achieved seizure freedom, the median time from ASM initiation to seizure cessation was 2.2 months among patients without relapse and 7.4 months among patients with relapse (hazard ratio, 0.67; 95% CI, 0.48-0.94; P =.02).

This study was limited by incomplete data, which accounted for 14.8% of indeterminate cases. Additionally, the researchers did not account for ASM choice or dosage.

The study authors concluded, “Despite increasing availability of newer-generation ASMs, prognosis has likely not improved. The first year following treatment remains a high-risk period for recurrent seizures, and most will have their first ASM fail. Optimizing choice of first ASM and early identification of failure may improve these outcomes.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.