Few Focal Epilepsy Cases Controlled by Initial ASM Treatment

Los Angeles — Only about 27% of patients newly diagnosed with focal epilepsy are seizure-free on initial anti-seizure medications (ASMs), new research suggested.

This is sobering information to pass on to patients with focal epilepsy who may have high expectations based on prior data. “Patients tend to expect things to happen quickly, study investigator Sarah Barnard, MD , research fellow, School of Translational Medicine, Monash University, Melbourne, Australia, told Medscape Medical News.

The study was presented on December 7 at the American Epilepsy Society (AES) 78th Annual Meeting 2024.

An International Collaboration

The study is part of the International Human Epilepsy Project (HEP), which focuses on new-onset focal epilepsy, one of the most common forms of the disorder. The researchers are aiming to identify factors that influence treatment response in this population.

For example, they will investigate how specific medications and coexisting conditions affect treatment outcomes. Ultimately, the goal is to enable the development of individualized treatment plans for patients, leading to faster and more effective improvements or potential cures for the condition.

“The investigators wanted to focus in on focal epilepsy and exclude patients with more severe phenotypes, such as those with developmental delays or significant brain injury,” said Barnard. Individuals with focal epilepsy are generally healthy, she added.

In addition, previous studies may have used differing definitions of seizure freedom, said Barnard.

The study included 448 patients, median age about 33 years and 60% women, with focal epilepsy who were enrolled at 34 tertiary epilepsy centers in the United States, Europe, and Australia within 4 months of initiating ASM treatment.

Participants were followed for up to 6 years (the median was 3.13 years). The median age at seizure onset was 29 years, and the median age of treatment initiation was 32 years. The most common first-line ASMs were levetiracetam (56.9%) and lamotrigine (16.5%).

Researchers used updated International League Against Epilepsy definitions. Seizure freedom is defined as no seizures for 12 months or three times the longest pretreatment seizure-free interval, whichever is longer.

Results showed that only 27% of patients were seizure-free in the first year after diagnosis even accounting for a 2-month “medication adjustment” period.

Managing Expectations

Although the study excluded individuals with more severe types of epilepsy, “we still identified a substantial proportion of treatment-resistant cases, suggesting that much more complex factors are at play,” said Jacqueline French, MD, a study coinvestigator and professor at the NYU Langone’s Comprehensive Epilepsy Center in New York City.

“I don’t think we adequately prepare our patients for the challenges of the first year, which can be quite turbulent,” French told Medscape Medical News.

However, the seizure freedom rate in this study is lower than previous estimates. “It’s much less than what was predicted in other studies, some of which quote around 50 to 55% seizure freedom on the first ASM,” said Barnard.

It’s not clear why there’s such a difference, although it may be related to a predominance in the HEP study of patients taking levetiracetam as the first-line ASM. “We didn’t directly look at the rate of treatment response or seizure freedom on levetiracetam,” which is something that will be addressed in a follow-up study, Barnard added.

The difference could be due to the study including only focal epilepsy patients, “who usually have a different treatment regime,” or it could be related to using updated definitions in this study, she said.

Results also showed that patients are at high risk during the first year of treatment, with two thirds experiencing ongoing or worsening seizures during this period. “People have ongoing seizures for the first year, even if they go on to become seizure-free,” Barnard noted.

Experiencing ongoing seizures has potential implications for driving and for employment, she added.

A self-reported history of a psychological disorder was a risk factor for increased treatment resistance. Upon enrollment, each participant completed the Mini International Neuropsychiatric Interview, which Barnard said is a diagnostic, rather than a screening, tool.

One of the team’s next research steps is to look more closely at the role of depression, anxiety, bipolar disorder, and suicidality on treatment response in this patient population, said Barnard.

Important for Patient Counselling

Commenting for Medscape Medical News, Patrick Kwan, MD, PhD, professor, Department of Neuroscience, Monash University, said the research is “very important” in terms of patient counseling.

“For someone newly diagnosed with epilepsy, starting the first medication can be both daunting and confusing, with many uncertainties,” said Kwan. “That’s why it’s valuable to know that nearly a third of patients may not respond to initial treatment.”

He noted that the patients in the study were recruited from major centers, which could attract a specific subset of individuals. “It’s possible that this patient population might represent more severe cases,” he explained.

Kwan also emphasized that the study did not examine the “patterns” of prescription drug choices, adding that he agreed this should be addressed in future analyses.

The researchers and Kwan reported no relevant disclosures.