Nearly 70% of patients with focal treatment-resistant epilepsy (FTRE) experience fewer seizures over time, new results of a multicenter study showed.

However, the improvements occurred independent of specific drugs, including antiseizure medications (ASMs) or device changes, suggesting that open-label studies reporting long-term seizure reduction may overstate treatment-related “disease-modifying” effects and that active management and natural progression — rather than a particular intervention — are responsible for seizure improvement in FTRE.

“Our findings challenge the assumption that once a patient with focal epilepsy has failed a certain number of antiseizure drugs, their chances of finding relief are small and not worth the effort,” lead author Ojas Potnis, MD, a resident in the Department of Neurology at the NYU Grossman School of Medicine, New York City, said in a release.

“These results offer hope that focal epilepsy will get better over time for most people,” co-principal investigator Jacqueline A. French, MD, professor of neurology at NYU Grossman School of Medicine, added.

The results were published online on October 20 in JAMA Neurology.

Time-Linked Seizure Improvement

The Human Epilepsy Project 2 is an observational study conducted at 10 US epilepsy centers from 2018 to 2021.

It included 146 patients with FTRE aged between 16 and 65 years (mean age, 40 years; mean epilepsy diagnosis age, 19.8 years; 57.5% women) who were followed for 18-36 months. Sufficient seizure data were provided by 126 participants.

All participants had failed at least four ASMs, including at least two due to inadequate seizure control. A total of 35 participants also had implantable devices.

The primary outcome was seizure frequency trends, assessed by rates of seizure freedom and reductions in seizure frequency.

Seizure and medication data were collected through the use of daily electronic diaries, monthly check-ins, medical record reviews, and three in-person visits at 6-month intervals.

Seizure frequency declined in 68.3% of participants during the second half of the study compared with the first.

There was also a mean modeled monthly seizure frequency reduction of 68.7% (95% CI, 52.9%-84.5%). The mean modeled percentage reductions in frequency for the cohorts providing data for up to 12 months, 12-24 months, and longer than 24 months were 67.8%, 36%, and 66%, respectively.

In addition, 12% had at least 3 months of seizure freedom at the last study contact, 7% had more than 6 months of freedom, and 3% had at least 12 months.

Seizure freedom did not differ significantly on the basis of age, sex, number of ASMs used at baseline, or epilepsy duration variance.

In the 69 participants with seizure data who had an ASM added to their therapy, 66.7% showed seizure frequency reduction.

Of the 146 participants, 80 (55%) had an ASM added during the study, and 67.5% of them reported a reduction in seizure frequency. However, only six achieved seizure freedom lasting at least 3 months.

Seizure trajectories after device implantation — including deep brain stimulation, responsive neurostimulation, or vagal nerve stimulation — did not differ significantly from those of participants without device implantation.

“Improvement in seizure burden over time independent of intervention type suggests cautious interpretation of open-label studies that posit disease-modifying effects to explain seizure improvement in similar time courses,” the investigators wrote.

Still, clinicians “should keep searching for the best treatment regimen for their patients no matter how many therapies they may need to try,” French said.

The study was funded by UCB, Neurelis, and SK Life Sciences. Potnis reported receiving grants from all three of the funders. French and two of the other investigators reported having numerous financial relationships, which are fully listed in the original article.