Abstracts

Rationale: The Human Epilepsy Project (HEP) is a multicenter prospective observational study of newly treated focal epilepsy patients aged 12-60 years. The primary objective is to identify predictors of treatment resistance. We investigated treatment change rates in a HEP cohort treated with antiepileptic drugs (AEDs) for at least 6 months. We also examined whether EEGs or MRIs obtained at enrollment were informative regarding AED response and tolerability, as determined by the current AED regimen (initial monotherapy, sequential monotherapies, dual therapy, or polytherapy).Methods: HEP participants recorded their AED usage using electronic seizure diaries, and HEP investigators reviewed data at regular intervals. Participating sites obtained EEGs and MRIs and submitted them to central cores, where they were reviewed and scored by expert HEP investigators. EEGs and MRIs were a mix of clinical studies and those obtained for research purposes. For this analysis, we included HEP participants with at least 6 months of AED treatment by a cut-off date in May 2015. Benzodiazepines were excluded. For participants with multiple MRIs or EEGs (or multiple findings on a single MRI or EEG), results were coded as single responses most relevant to an epilepsy diagnosis.Results: We identified 171 participants with at least 6 months of AED treatment (median: 461 days; range: 183-1080 days). Of those, only 40% remained on their initial monotherapy at the end of the study epoch; 44% were on an alternate monotherapy, 15% were on dual therapy, and 1 participant was on polytherapy. The median time to a second AED exposure was 81 days. In our cohort, 45% had a normal EEG, 15% had a seizure captured (ictal EEG), 22% had interictal epileptiform discharges, and 14% had focal slowing. Of those with a normal EEG, nearly 50% remained on their initial monotherapy; results were similar for those with interictal discharges or focal slowing. In participants with an ictal EEG, only 9% remained on initial monotherapy; the remainder were on sequential monotherapies or dual therapy. By contrast, there was no appreciable difference in the current AED regimens between the brain MRI groups (categorized as normal, abnormal, or with incidental findings).Conclusions: A minority of patients with focal epilepsy remain on their initial AED monotherapy when studied 6-36 months after treatment initiation; nearly two-thirds are on a new AED regimen. Capture of an ictal EEG may reflect a high seizure burden and increased likelihood of change from the initial antiepileptic drug. Neither interictal EEG findings nor MRI classification had much predictive value for subsequent AED changes in our cohort. Further investigation is needed to identify variables that impact the EEG and MRI yields and AED changes observed in our cohort. Funding source: The Epilepsy Study Consortium (ESCI), a non-profit organization funded by industry, philanthropy and foundations (UCB Pharma, Pfizer, Eisai, Lundbeck, Finding A Cure for Epilepsy and Seizures, The Andrews Foundation, Friends of Faces and others).