Abstracts

Rationale: In two previous studies, we examined the comparative efficacy of antiepileptic drugs (AEDs) given to developmentally disabled patients with medically refractory epilepsy (Poolos et al., Neurology 2012; Poolos et al., Epi Behav, 2017). We found that only lamotrigine plus valproate (LTG/VPA) yielded significant reduction in seizure frequency compared to patients' baseline, and that polytherapy had only modest benefits over monotherapy. In the present study, we sought to similarly analyze AED efficacy in a community-based sample of patients whose seizures and AEDs were documented using the SeizureTracker.com (ST) online and mobile diary system. We hypothesized that similar patterns of AED comparative efficacy would be seen in community-based subjects as in institutionalized patients. Methods: We obtained anonymized ST patient data consisting for each user of the dates of seizure occurrences, the type of seizure, and the AEDs being administered. Criteria for analysis of user data were: at least 12 months of seizure data with concurrent documentation of AED administration; exposure to at least two unique AED regimens of up to three drugs each; and an average seizure frequency of at least 6 per year. We calculated the average seizure frequency seen during each unique AED regimen and compared it within-subjects to the average (baseline) frequency seen during all other regimens. Results: 303 users met criteria for analysis. The average age was 19.3 years. 14% of users documented a genetic syndrome (e.g. Dravet, tuberous sclerosis, and Lennox-Gastaut). Users documented an average of 9.5 seizures per month. We analyzed an average of 3.6 years of data per user. Within-subjects comparisons showed that administration of two AEDs at a time (duotherapy) compared to monotherapy showed no benefit of duotherapy (0.6% increase in seizure frequency, n=188). Likewise, three AEDs given together yielded a 0.3% increase in seizure frequency over duotherapy (n=99). In comparisons of AED regimen efficacy vs. baseline therapy, no regimen demonstrated significant superiority. LTG/VPA showed the largest magnitude of seizure frequency reduction (40.1% reduction vs. baseline) but this was not statistically significant (n=12; p=0.10). The combination of levetiracetam and LTG showed a 29.7% increase in seizure frequency vs. baseline of borderline statistical significance (n=26; p=0.04). Conclusions: We found similar trends in AED comparative efficacy in community-based patients as in institutionalized patients with regard to the efficacy of polytherapy versus monotherapy, with no additional benefit of polytherapy compared to monotherapy. Although LTG/VPA showed the largest magnitude of seizure frequency reduction versus baseline, only a small number of users were exposed to this regimen and the effect was not statistically significant. Accumulation of additional user data may clarify whether LTG/VPA or other regimens provide superior seizure control. We conclude that online seizure diaries provide a potentially important new tool for analysis of AED efficacy in refractory epilepsy. Funding: Funding from the Lennox-Gastaut Foundation (NPP). SeizureTracker.com data dissemination was administered through an agreement with the International Seizure Diary Consortium and National Institutes of Health.