Abstracts

Rationale: The Human Epilepsy Project is a multicenter study that enrolls participants with newly treated focal epilepsy and follows them prospectively. Previous randomized controlled studies comparing levetiracetam (LEV) and carbamazepine (a type of sodium channel blocker, NAB) revealed no difference between the two as first-line antiepileptic drug (AED). Here we compare treatment response rates of LEV versus NAB as first line AED monotherapy in participants who had a consistently high seizure frequency prior to treatment initiation. Methods: We identified 50 participants who reported ?- 1 seizures a month for the 6 months prior to starting AEDs, kept good seizure diaries, and had at least 6 months follow-up after starting AEDs. Participants were separated into two categories based on first AED initiated: levetiracetam (LEV, N=27) versus sodium channel blocker (NAB, N=23). NABs included: lamotrigine (N=14), phenytoin (N=3), carbamazepine (N=3), oxcarbazepine (N=3). Outcomes were 6 month seizure freedom (6MSF) and terminal seizure freedom (TSF) within and across groups, and on first, second and third AED within group. Results: Demographics were similar between groups (see Table 1). Pre-treatment seizure duration and frequency for all patients and within groups is shown in Table 2. 48% (24/50) of participants achieved 6MSF on first AED, while 40% (20/50) achieved TSF. For participants who received LEV as their first AED, 37% (10/27) were 6MSF and 30% (8/27) reached TSF. By contrast, for participants receiving an NAB as their first drug, 61% (14/23) were 6MSF and 52% (12/23) achieved TSF (p=0.1 for both). For participants who did not respond to LEV initially, 37% (7/19) and 32% (6/19) achieved 6MSF and TSF, respectively, on NAB as second AED. Participants who did not respond to NAB as first AED also failed to achieve 6MSF on LEV (0/9) (p=.07). Two NAB participants (9%) were TSF on their third AED: one on GBP and one on ZNS. Two participants (7%) were not on LEV monotherapy long enough to assess efficacy; in the NAB group two participants (9%) were not on phenytoin monotherapy long enough to assess efficacy. 30% (8/27) of first AED LEV participants were refractory, while 22% (5/23) of the NAB group were refractory. The majority of the participants who were started on LEV initially required addition of or switching to a second AED, either due to side effects or poor seizure control (23/27, 85%), while less than half who were started on an NAB required a second AED (11/23, 48%) (p=.025). The time to second AED was not markedly different between the two groups. Conclusions: Our results suggest that patients initiated on LEV monotherapy have worse 6MSF and TSF compared to those initiated on NAB, and often require addition/transition to a NAB to achieve improved outcomes. In addition, our findings suggest that despite their high seizure frequency and long duration prior to treatment, participants had good seizure freedom rates. Larger participant numbers are needed to confirm our results and elucidate pathophysiological mechanisms. Funding: The Epilepsy Study Consortium (ESCI) is a non-profit organization dedicated to accelerating the development of new therapies in epilepsy to improve patient care. The funding provided to ESCI to support HEP comes from industry, philanthropy and foundations (UCB Pharma, Eisai, Pfizer, Lundbeck, Sunovian, The Andrews Foundation, The Vogelstein Foundation, Finding A Cure for Epilepsy and Seizures, Friends of Faces and others.