Abstracts

Rationale: To analyze the efficacy and tolerability of perampanel (PER) following its introduction.  We aimed to assess: 1) Outcomes according to patient’s clinical profiles and the mechanism of action (MoA) of concomitant antiepileptic drugs (AEDs); 2) The effects of PER on existing or emergent psychiatric and behavioural symptoms and its effect on quality of life (QOL). Methods: Patients commenced on PER at two epilepsy centers in Melbourne, Australia were consecutively identified.  An unselected nested subset of patients (WD) also underwent more detailed prospective assessment, while the remainder of patients were retrospectively analyzed from medical record review.  6 and 12- month efficacy endpoints were at least a 50% reduction in seizure frequency (responders) and complete seizure freedom following 12 weeks dose titration and from onset of PER. Tolerability outcomes were the cessation of PER for any reason, cessation due to side-effects and censoring due to inefficacy or tolerability. In the prospective cohort standardized validated questionnaires were administered at 0, 1, 3, 6 and 12 months using the:  modified Semi-Structured Seizure Interview (SSI), Liverpool Adverse Events Profile (LAEP); Quality of Life in Epilepsy-Patient-Weighted (QOLIE-10-P); Neurological Disorders Inventory Epilepsy (NDDI-E) and a patient and carer irritability Questionnaire.  Results: 160 patients (75 prospective for at least 3 months at PER onset, 85 retrospective) were included and followed up for a median of 6 months. The median number of prior Antiepileptic drugs (AEDs) was 6 and the median number of current AEDs 2.6, all patients had never experienced more than 6 months of seizure freedom since disease onset with 99% having ILAE-defined drug-resistant epilepsy. PER retention was 73% at 12 months.  PER was associated with responder and seizure freedom rates of 30.6% and 9.4% at 6 months. There was some evidence that six-month responders were more likely to be treated with a concomitant GABA analogue (41% vs. 26%, p = 0.074).  85% of the prospective cohort had initial or emergent side effects, with behavioural, sleep-related or ataxia being the most frequently reported (56%, 52% and 38% respectively).  However, these side-effects diminished during the observation period with a significantly improved mood NDDI-E score (p=0.023), reduced patient-reported irritability scores (p=0.001) and overall improvement in QOL (mean difference 14.2, 95% CI: 5.2-33.5 p=0.036) observed after 6 months of PER which was maintained during follow-up. Conclusions: Even in this highly refractory cohort of patients with epilepsy 30.6% responder and 9,4% seizure freedom rates can be observed 6 months following the introduction of PER.  Importantly, improved irritability, mood and quality of life was observed and maintained in patients on PER after 6 months of treatment.  Funding: This study was supported by an investigator-initiated research grant from Eisai Pharmaceutical Australia.