Abstracts

Rationale: Patients with treatment resistant epilepsy may try and fail over a dozen anti-seizure medications (ASMs). The Human Epilepsy Project 2 (HEP2) was a prospective, observational multicenter US study with the goal of identifying clinical characteristics and biomarkers predictive of disease outcome, progression, and treatment response in participants with treatment-resistant focal epilepsy. Here, we report on the lifetime and current ASM profiles for these patients, to determine US treatment patterns and more and less successful interventions.

Methods: All subjects had focal epilepsy, at enrollment were 16-65 years old, had failed 4 ASMs or more (at least 2 due to failure of seizure control) and were receiving at least 1 ASM. Subjects were recruited from 10 US epilepsy centers starting 7/31/2018 and were followed for 18-36 months. Subjects provided data at initial visit on demographics, medical hx, seizure hx, EEG and MRI results, past and current ASMs. Lifetime ASM is any ASM taken in the past or currently. Current ASMs are taken at baseline.

Results: 146 actively enrolled participants provided data on lifetime ASMs. Participant average age was 39.7 ± 12 years old, 84/146 (57.5%) female, 62/146 (42.5%) male. The average age at participant diagnosis with epilepsy was 39.7 ± 12 years old, and the average duration of epilepsy was 20.2 ± 13.3 years. The average lifetime ASM use was 8 ± 4 ASMs. Levetiracetam was the most commonly used ASM overall, with 135 subjects (92.5%) reporting lifetime use. Lifetime use of other ASMs in order of frequency were:   Lamotrigine: 108 (74.0%) Lacosamide: 98 (67.1%), Carbamazepine: 82 (56.2%), Topiramate 73 (50.0%), Clobazam 73 (50.0%), Zonisamide 71 (48.6%), Oxcarbazepine 70 (48.6%), Phenytoin 65 (44.5%), Phenobarbital 39 (26.7%), Brivaracetam 25 (17.1%), Eslicarbazepine 22 (15.1%) (Table 1). Lifetime use for all drugs other than brivaracetam, phenytoin, zonisamide was reported by more women than men.  Current/Lifetime use of ASMs, in order, were: Eslicarbazepine 14/22 (63.6%), Brivaracetam 15/25 (60%); Clobazam 42/73 (57.5%); Lacosamide: 53/98 (54.1%) Lamotrigine: 47/108 (43.5%) Levetiracetam 52/135 (38.5%) Zonisamide 27/71 (38.0%); Oxcarbazepine 22/70 (31.4%); Carbamazepine: 22/82 (26.8%) Topiramate 15/73 (20.5%); Phenobarbital 5/39 (12.8%); Phenytoin 7/65 (10.8%) (Table 2).

Conclusions: Cataloguing lifetime and current ASMs for patients with refractory epilepsy provides direction for understanding which medications are tolerated and provide benefit. While levetiracetam demonstrated the highest lifetime use (92.5% of subjects), only 38% subjects reported use at baseline. Phenytoin demonstrated the lowest rate of continuation at 10.8%. The higher reporting of overall ASM exposures by women is of unclear significance, and could be a reporting bias. Several ASMs (eslicarbazepine, brivaracetam) had low frequency of use with high retention that might be explained by recent market introduction. Lacosamide and lamotrigine had relatively high use and high retention, suggesting a good clinical efficacy/tolerability.

Funding: UCB, Neurelis, and SK Life Sciences.