Abstract Details

Title Does Treatment-resistant Epilepsy Get Better or Worse Over Time?

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S24 - Epilepsy Clinical Syndromes and Management (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Background

Does focal treatment resistant epilepsy (FTRE) improve or worsen over time? This is an important question, as many open label long-term extension studies of anti-seizure medications (ASMs) and devices suggest improvement over time, and invoke a possible disease modifying effect. The Human Epilepsy Project 2 is a prospective, observational, multicenter US study aimed at identifying treatment response in participants with FTRE. Here, we report trends in seizure frequency for participants during the study.

Objective

Characterize focal treatment resistant epilepsy seizure frequency natural history.

Design/Methods

All participants had FTRE, failed ≥4 ASMs, were receiving ≥1 ASM, and were followed ≤36 months. Seizure frequency data were collected via daily electronic seizure diaries, monthly coordinator check-ins, medical records. To prevent confounding by dropouts, we compared first half of follow-up to second half within each participant. Three cohorts were also created based on follow-up times of <12, 12-24, >24 months. We examined all data in a linear mixed model with response variable of monthly seizure counts and independent variable of follow-up month to examine slopes of the seizure counts over time within each cohort.

Results

128 actively enrolled participants provided seizure frequency data over time. 68.2% experienced seizure frequency reduction in the second half of their follow-up compared to the first half. Linear regression analysis demonstrated continued improvement of approximately 1 seizure/month. The trend in the LS Means seizure count estimated from the models for each cohort showed similar decreases in estimated seizure counts over the projected months of follow-up.

Conclusions

Our data suggests improvement of seizures over time in FTRE. The data cannot distinguish between “natural history” and effects of ongoing active management. However, these data support the need for cautious interpretation of open-label studies that report improvement trends over time. Future analyses of our data will address impact of specific medication interventions during the study.

Authors/Disclosures
Ojas Potnis PRESENTER	Mr. Potnis has nothing to disclose.
Gabriel Biondo (University of Notre Dame)	Mr. Biondo has nothing to disclose.
Rachel Sukonnik	No disclosure on file
Caitlin Grzeskowiak	No disclosure on file
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein-Buendel Incorporated, Medimmune/Viela Bio, Medday, Merck/Serono, Neurogenesis LTD, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Regeneron, Reckover Pharmaceuticals, Roche, TG Therapeutics.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Biolinerx, Brainstorm Cell Therapeutics, Bristol Meyers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Mapi Pharmaceuticals LTD, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics,Prothena Biosciences, Novartis, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, NHLBI (Protocol Review Committee), University of Texas Southwestern, University of Pennsylvania, Visioneering Technologies, Inc.. Dr. Cutter has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Joseph Medina (NYU Langone BRAIN Program)	No disclosure on file
Jacqueline French, MD, FAAN (NYU Comprehensive Epilepsy Ctr)	Dr. French has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Epilepsy Foundation. The institution of Dr. French has received research support from Epilepsy Study Consortium/ Epilepsy Foundation (Funded by UCB). The institution of Dr. French has received research support from GW/One8 Foundation/FACES. The institution of Dr. French has received research support from NINDS. The institution of Dr. French has received research support from Xenon. The institution of Dr. French has received research support from Cerevel. The institution of Dr. French has received research support from FACES. The institution of Dr. French has received research support from UCB. The institution of Dr. French has received research support from Epilepsy Study Consortium. The institution of Dr. French has received research support from UCB. Dr. French has received personal compensation in the range of $100,000-$499,999 for serving as a Chief Medical/Innovation Officer with Epilepsy Foundation. Dr. French has a non-compensated relationship as a Consultant with Angelini that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Alterity Therapeutics Limited that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Bright minds Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cerecin Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cognizance Biomarkers that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Arvelle that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Beacon biosignals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Advisory Board with Biohaven Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Bloom Science Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with BridgeBio Pharma Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant, scientific advisory board with Camp4 Therapeutics Corporation that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, Scientific Advisory Board with Cerebral Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Cerevel that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a SAB with Coda Biotherapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Genentech Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Crossject that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Eisai, that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Eliem Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Encoded Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with iQure Pharma that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Engrail that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a SAB with Epihunter that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a SAB with Epiminder that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Epitel Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Equilibre BioPharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Greenwich Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Grin Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with GW Pharma that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Janssen Pharmaceutica that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Jazz Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Knopp Biosciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Lipocine that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with LivaNova that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Longboard Pharmaceuticals that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Lundbeck that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Marinus that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Modulight Bio that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Leal therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neumirna Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant,SAB with Neurocrine that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neuroelectrics USA Corporation that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Neuronetics Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Ono Pharmaceutical Co that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Otsuka Pharmaceutical Development that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with Ovid Therapeutics Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Paladin Labs Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Rapport Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Praxis that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with PureTech LTY Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with SK Life Sciences that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Stoke that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Supernus that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Takeda that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant, SAB with UCB Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Ventus Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consulting, steering committee with Xenon that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consultant with Korro Bio Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with NeuroPro Therapeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory board with Receptor that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory board with Sage Therpeutics that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Advisory Board with Third Rock Ventures that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consultant with Vida Ventures Management that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Pfizer that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Agrithera, Inc that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a consulting with Autifony therapeutics, Unlimited that is relevant to AAN interests or activities. Dr. French has a non-compensated relationship as a Consulting with Baergic Bio that is relevant to AAN interests or activities.