PND59 Determining the Relationship of Seizures, Seizure-Free Days (SFDS) and Other Predictors of Health-Related Quality of Life (HRQOL) in Patients with Dravet Syndrome (DS) and Their Carers

Abstract

DS is a rare, early onset, lifelong epileptic encephalopathy characterised by frequent and severe seizures. High seizure frequency is associated with behavioral and physical developmental comorbidities with a substantial burden to patients’ and carers’ HR-QoL. Reducing convulsive seizure frequency and increasing SFDs is a primary treatment goal for patients. This study explored the impact of increasing SFDs on patients’ and carers’ HR-QoL. In fenfluramine registration studies, patients (or proxies) completed the Pediatric Quality of Life Inventory. These patient HR-QoL data were mapped to EQ-5D-Y to provide patient utilities. Carer utilities were collected directly (EQ-5D) and mapped to EQ-5D-3L. A linear mixed effects regression model was developed to explore relationships between patient EQ-5D-Y, and clinically relevant variables: age group, frequency of SFDs per 28-days, motor impairment(s) and treatment dose. A linear panel regression model examined the relationship between SFDs and carer HR-QoL. Adjusting for age and underlying comorbidities, results from the patient regression model showed “frequency of SFDs per 28-days” was a significant predictor of HR-QoL (gain in EQ-5D utility of 0.005 per additional SFD, p<0.001). The carer linear panel model also showed “frequency of SFDs per 28-days” as a significant predictor of HR-QoL (gain in EQ-5D-3L utility of 0.014 per additional SFD, p<0.001). For example, a typical patient aged <6 years with 2 co-morbidities and 10 SFDs per 28-days would have an EQ-5D utility of 0.48. If on fenfluramine, SFDs increased to 20 or 28 (“seizure-free”) per 28 days, patient utility would rise 11.4% and 20.5%, and their carer’s utility by 27.7% and 49.8%, respectively. This regression framework provides a useful method in determining the HR-QoL impact that frequent seizures have on DS patients and their carers; highlighting that effective antiseizure treatments that durably increase SFDs, also improve patients’ and carers’ QoL in a directly quantifiable manner.