Abstracts

Rationale: Perampanel (PER) is a new generation Anti-Seizure Medication (ASM), which has a novel mechanism of action by inhibiting excitatory neurons via AMPA receptors. PER has been FDA approved in partial-onset seizure treatment as adjunctive therapy since 2012, and monotherapy use was approved in 2017. We aim to evaluate the efficacy and tolerability of PER in treatment of refractory epilepsy. Methods: In this retrospective study, we included patients with refractory epilepsy (receiving two or more ASMs for seizure control) who were treated with PER at Boston Children’s Hospital between January 2014 and January 2018. Demographic information, seizure characteristics, seizure frequency, PER administration information and adverse effects were acquired utilizing a standardized data acquisition tool. Response to treatment was defined as greater than 50% reduction in seizure frequency at the last follow-up as compared to baseline. Treatment response, dosage and tolerability were evaluated at first and last follow up. Patients with incomplete information were excluded from the analysis.  Results: We reviewed 67 patients who were treated with PER, and based on complete data and follow up information, we included 59 patients. 27 (46%) patients were females, and the median age was 12 years (IQR: 9-19, range: 1- 34 years). Median follow-up durations were 3 months (IQR; 2-4) and 8 months (IQR: 5-15), at first and last follow-up, respectively. After treatment, seizure frequency was significantly decreased at the first follow-up [median, IQR; 30(4-150) vs. 120(10-120), p=0.001] and last follow-up [median, IQR; 30(2-120) vs. 120(10-120), p=0.007], as compared to baseline. At the last follow-up 26 (44%) patients had a seizure reduction of >50%, 11 (19 %) patients had 50% seizure reduction, and 22 (37%) patients discontinued PER due to adverse effects (15, 25%) or lack of efficacy (7, 12%). 14 (24%) patients became seizure free at their last follow-up, and among these, 7 (12%) were less than 12 years of age.  Responders of PER treatment showed significantly greater seizure reduction at the first (p=0.014) and last follow-up (pp=0.001), and had longer duration of treatment (p=0.037)  as compared to non-responders. 21 (36%) patients experienced adverse effects, and behavioral changes (13, 22%), dizziness (13, 22%), irritability (4, 6.8%) and somnolence (4, 6.8%) were more frequent. Patients receiving 1 mg (IQR: 1-2) PER presented with fewer adverse effects than patients receiving 2 mg (IQR: 1.2-2) as initiation dose (pp=0.2) and showed significantly lower adverse effects (19% vs. 73%, p<0.002) compared to adolescent patients (12 to 18 years; n=11). Conclusions: Perampanel had a good response rate in pediatric patients with pharmacologically intractable epilepsy, with greater response rate and fewer adverse effects in younger children. Further sub-analyses in larger populations are needed to validate the findings from this study. Funding: This study was funded by Eisai Inc.