Determining the Relationship between Seizure-Free Days and Other Predictors of Quality of Life in Patients with Dravet Syndrome and Their Carers

ObjectivesDravet syndrome (DS) is a rare, lifelong epileptic encephalopathy characterised by frequent and severe seizures associated with premature mortality. Typically diagnosed in infancy, patients also experience progressive behavioural, motor-function and cognitive decline. Twenty percent of patients do not reach adulthood. Quality of life (QoL) is impaired for both patients and their carers. Reducing convulsive seizure frequency, increasing seizure free days (SFDs) and improving patient/carer QoL are primary treatment goals in DS. This study explored the relationship between SFDs and patients and carers QoL to inform a cost-utility analysis of fenfluramine. MethodsIn fenfluramine registration studies, patients (or their carer proxies) completed the Paediatric Quality of Life inventory (PedsQOL). These data were mapped to EuroQol-5 Dimensions Youth version (EQ-5D-Y) to provide patient utilities. Carer utilities were collected using EQ-5D-5L and mapped to EQ-5D-3L to align patient and carer QoL on the same scale. Linear mixed-effects and panel regression models were tested and Hausman tests identified the most appropriate approach for each group. On this basis, a linear mixed-effects regression model was used to examine the relationships between patient EQ-5D-Y, and clinically relevant variables (age, frequency of SFDs per 28-days, motor impairments and treatment dose). A linear panel regression model examined the relationship between SFDs and carer QoL. ResultsAdjusting for age and underlying comorbidities, the patient regression model showed that SFDs per 28-days was a significant predictor of QoL. Each additional patient-SFD increased utility by 0.005 (p<.001). The carer linear panel model also showed that increasing SFDs per 28-days was a significant predictor of improved QoL. Each additional SFD increased carer utility by 0.014 (p<.001). SignificanceThis regression framework highlights that SFDs are significantly correlated with both patients and carers QoL. Treatment with effective antiseizure medications that increase SFDs, directly improves QoL for patients and their carers. Short summaryDS patients experience daily severe seizures with progressive deterioration in their physical, cognitive and behavioural development ("comorbidities"), which substantially impacts the QoL of patients and their carers. Reducing seizure frequency and increasing Seizure Free Days (SFDs) are key treatment goals. This study examined the relationship between seizures and patients and carers QoL. Regression analyses were conducted using data from the fenfluramine registration studies and confirmed increasing SFDs directly, and quantifiably, improved patient and carer QoL (utilities per additional SFD per 28-days: patient=0.005 and carer=0.014). These analyses demonstrate that effective antiseizure treatment can directly and profoundly improve patients and carers QoL.