Loading ...

Most newly diagnosed patients with focal epilepsy continued to have seizures for a year or more after starting antiseizure medications (ASMs), results from the latest Human Epilepsy Project (HEP) analysis showed.

Nearly one quarter of patients developed treatment resistance in the first year, researchers found, with seizure activity persisting in two thirds of patients long after initiating ASM therapy.

Investigators said the study provides important prognostic information for these patients and highlights that, despite newer-generation ASMs, overall prognosis has not markedly improved.

“Our findings suggest that those with focal epilepsy should expect a long adjustment period as their healthcare provider determines the best treatment regimen for them,” the study author Jacqueline French, MD, professor in the Department of Neurology at NYU Grossman School of Medicine, New York City, and co-principal investigator of HEP, said in a press release.

The research was published online on August 25 in JAMA Neurology.

A Risky First Year

Focal epilepsy accounts for about 60% of all epilepsy cases.

In this HEP analysis, investigators followed 448 patients aged 12-60 years with focal epilepsy, which accounts for about 60% of all epilepsy cases.

Participants from 34 epilepsy centers in North America, Europe, and Australia were enrolled within 4 months of starting ASM therapy and followed for a median of 3 years. The median age at the treatment initiation was 32 years; 60% of the participants were women.

By study end, nearly 60% were seizure-free, while 23% developed treatment resistance, defined as the failure of two adequate ASM trials. Median time to seizure freedom was 12.1 months.

Those who remained seizure-free achieved it sooner than those who relapsed (median, 2.2 months vs 7.4 months), and about half of resistant patients were identified within 6-8 months.

“More than two thirds of participants had ongoing or worsening seizures in the first year of treatment,” the authors wrote. “This suggests that in the first 12 months of receiving a diagnosis of focal epilepsy, patients will have a greater likelihood of experiencing recurrent seizures than not.”

Choosing the Right ASM

Several factors may explain the treatment lag. ASMs are often titrated slowly to minimize adverse effects, delaying therapeutic dosing. Patients may require multiple trials because of tolerability issues or poor efficacy.

In this study, 57% of patients were prescribed levetiracetam as their first ASM, a common choice among neurologists because of the drug’s versatility in treating different seizure types and few drug interactions.

However, only about one quarter of the cohort achieved seizure freedom on their first medication. Prior evidence suggests lower success rates with levetiracetam than with sodium channel blockers, which may partly explain the results.

The analysis also identified prognostic markers of resistance. Patients with a self-reported history of depression, anxiety, or other psychiatric disorders were nearly twice as likely to develop resistance (relative risk [RR], 1.78) as those without such histories.

Pretreatment seizure frequency was also important. Individuals with infrequent seizures were less likely to develop resistance (RR, 0.41) and more likely to respond to medication than those with very frequent seizures.

While the first year is likely one of high seizure risk, the authors emphasized that ongoing seizures in the first year do not necessarily indicate forthcoming treatment resistance.

“Optimizing choice of first ASM and early identification of failure may improve these outcomes,” they wrote.

The study was funded by the Epilepsy Study Consortium. French reported receiving salary and research support from the Epilepsy Foundation and the Epilepsy Study Consortium and having consulting or advisory roles with multiple pharmaceutical companies, including UCB, Eisai, Pfizer, Lundbeck, and Sunovion. Full disclosures can be found in the original article.