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New Data from The Human Epilepsy Project Looks at Treatment Outcomes Over a Lifetime

Data from the Human Epilepsy Project 2 (HEP2) provides new insights on which antiseizure medications (ASMs) are well tolerated and could offer benefits for people with refractory epilepsy, researchers said at the American Epilepsy Society annual meeting in December.

HEP2, a prospective observational study, was designed to determine whether biomarkers and clinical characteristics can predict disease outcome, progression, and the response to treatment in patients with focal epilepsies.

The study investigators recruited 146 patients from 10 epilepsy centers throughout the United States and followed them, starting in 2016, for up to 36 months. Participants had focal epilepsy and had failed at least four ASMs; the average pre-study lifetime use included eight different ASMs.

The investigators collected information on demographics, medical history, seizure history, EEG and MRI results, and past and current ASM drug history. At the start of the study, patients were taking at least one ASM. Forty-five of the study subjects were diagnosed before the age of 10. The average age at baseline was 39.7 years.

“As many as one-third of patients with epilepsy can be prescribed a variety of ASMs for a decade or longer without a benefit on reducing seizure frequency," said Jacqueline A. French, MD, FAAN, professor of neurology at the Comprehensive Epilepsy Center of the NYU Grossman School of Medicine and chief medical/innovation officer of the Epilepsy Foundation, which sponsored the study.

“We want to know what gets people to [become] seizure-free as soon as possible," Dr. French said. “We want to shorten the path for these patients to find the right treatments and understand why some medicines work in some patients and others don't."

The HEP2 data contains information on the drugs participants have tried and are no longer taking as well as which drugs were still around when they joined the study, Dr. French said.  

The analysis revealed, among other findings, that levetiracetam was the most commonly used ASM overall, with 92.5 percent reporting lifetime use, followed by lamotrigine at 74 percent, lacosamide at 67.1 percent, carbamazepine at 56.2 percent, and topiramate and zonisamine at 50 percent each.

While it was not surprising that levetricacetam was the most commonly prescribed ASM over a patient's lifetime, it was important to see that it is one of the drugs not likely to be retained, Dr. French said.

After they started an ASM, 63.6 percent of participants continued to use eslicarbazepine; 60 percent, brivaracetam; 57.5 percent, clobazam; and 38 percent, zonisamide. Phenytoin had the lowest rate of continuation at 10.8 percent, while eslicarbazepine and brivaracetam had low frequency of use with high retention. Finally, lacosamide and lamotrigine had relatively high use and high retention, suggesting good clinical efficacy and tolerability.

Dr. French and Texas A&M medical student Ojas Potnis, who presented the findings at the AES meeting, will continue to analyze data from the HEP2 study.

“These patients have been followed for two years, and we will be looking to see who is seizure-free and why," Dr. French said.

“The Human Epilepsy project is a remarkable and multifaceted research effort for people living with epilepsy," said Andreas V. Alexopoulos, MD, MPH, a staff physician at the Cleveland Clinic Epilepsy Center and the Lerner Research Institute who also is the neurosciences course director at Lerner College of Medicine.

“A systematic examination of lifetime and current antiseizure drug use in patients with drug-resistant epilepsy allows us to catalog patterns of medication use. These data could help us understand which drugs are better tolerated and provide sustained benefit for our patients with drug-resistant focal epilepsy."               

Dr. Alexopoulos noted that observational studies have limitations, however. “The quality of the data in similar studies is dependent on appropriate documentation in the medical record and participant recall," he said.

“It is imperative to remember that the results of any observational study cannot be used to demonstrate causality," Dr. Alexopoulos added. “Sources of bias and confounding still exist in well-designed observational studies and should be considered when describing the implications of the study and extending its conclusions to the wider population of patients beyond the study cohort."            

​Still, Dr. Alexopoulos added, “such studies can provide a foundation that will allow us to identify specific clinical characteristics and potential biomarkers which could be harnessed in the future to predict disease course, outcome, and treatment response."

Dr. French disclosed that she received travel compensation from Angelini Pharma S.p.A., Cerevel, Clinical Education Alliance, NeuCyte Inc., Neurocrine, Praxis, and Xenon.

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