Abstracts

Rationale: With the acceleration of ASM development, there are increasing options for physicians to select to improve seizure control. The Human Epilepsy Project 2 (HEP2) is a prospective, observational, multicenter US study with the goal of identifying treatment responses in participants with FTRE. Here, we evaluate which newly released ASMs were attempted before others to understand practice patterns in ASM selection.

Methods: All participants had FTRE, failed at least 4 ASMs, were receiving at least 1 ASM, and were followed up to 36 months. Medication data prior to and currently at study start were collected at initial visit, and medication data was collected throughout the study via electronic seizure diaries, monthly coordinator check-ins, and medical records. We selected 2 groups for evaluation: ASMs that were released between 2008-2013 (Lacosamide, Clobazam, Perampanel, Eslicarbazepine, early group) and ASMs that were released between 2016-2019 (Brivaracetam, Cenobamate, Epidiolex, late group). Subjects who initiated medications in the late group, and had complete medication data were analyzed to determine average trial order per ASM in individual subjects. Also, for each initiation of an ASM in the late group, we evaluated whether or not each ASM in the earlier (already available) group had been tried.

Results: 73/135 of subjects who had attempted the selected ASMs had complete medication data for analysis. In this cohort, average order trialed per ASM were: Lacosamide(1.41), Clobazam(1.86), Brivaracetam(2.35), Eslicarbazepine(2.38), Perampanel(2.71), Epidiolex(3.13), Cenobamate(3.23). Of Brivaracetam, cenobamate, and epidiolex, Brivaracetam was trialed before the earlier release group the greatest percentage of the time, while Epidiolex skipped the earlier release group the least (Table 2). Brivaracetam, Cenobamate, Epidiolex were trialed more frequently in the absence of a trial of Perampanel and Eslicarbazepine than Lacosamide and Clobazam.


Conclusions: Average order trialed per ASM matched their order by release dates, except for Brivaracetam and Perampanel, which were trialed 3rd and 5th, respectively, despite being 5th and 3rd by release date order and being separated by 4 years. In addition, Brivaracetam was trialed ahead of ASMs in the early group most often, possibly due to its earlier release date and the fact that Epidiolex is not approved for focal epilepsy. The more recently approved ASMs were used before Perampanel and Eslicarbazepine more than 63% and 75% of the time, respectively, suggesting that clinicians had more optimism about the newer ASMs than these older ones. We show that while ASMs were trialed on average in order of their release date, there could be some preferences. Future analysis of these and other ASMs could provide understanding of physician preferences driving ASM choices.

Funding: The HEP2 study was funded by UCB, Neurelis, & SK Life Sciences.