Number of Needed to Treat (NNT) to Achieve Seizures Reduction or Seizure Freedom in Dravet Syndrome in France: Results From an Itc of Stiripentol vs Fenfluramine and Cannabidiol and the Economic Implications

OBJECTIVES: DS is a rare, highly refractory developmental and epileptic encephalopathy in children where only three treatments on top of conventional antiseizure medications are indicated. The objective of this study was to evaluate the NNT of stiripentol, fenfluramine and cannabidiol (vs. placebo) to achieve a given level of seizure reduction or freedom, and the cost implications.

METHODS: Proportion of patients achieving reductions from baseline in monthly convulsive seizure frequency (MCSF) of >50% and 100% were derived from an indirect treatment comparison of RCTs data of stiripentol, fenfluramine and cannabidiol (on top of standard antiseizures medications) vs. placebo. NNTs were calculated for pairwise comparisons versus placebo with the inverse of Absolute Risk Difference. Annual drugs costs per patient were calculated based on French prices and multiplied by their respective NNTs to estimate the average annual cost per patient achieving a >50% and 100% reduction in MCSF.

RESULTS: For the >50% reduction, stiripentol and fenfluramine were numerically the most effective (NNT=2) vs. cannabidiol (NNT=6). For seizures freedom, stiripentol (NNT=3) was statistically superior to both fenfluramine (NNT=10) and cannabidiol (NNT=25). This translates into annual costs for one adult to achieve 50% and 100% reduction of convulsive seizures of 25.530€, 38.294€ for stiripentol, 62.427€; 312.137€ for fenfluramine and 280.339€; 1.168.080€ for cannabidiol respectively. For children, annual cost of stiripentol was 12.765€; 19.147€ to achieve >50% and 100% reduction respectively whereas they are 50.422€; 252.111€ for fenfluramine and 140.170€; 584.040€ for cannabidiol.

CONCLUSIONS: This analysis puts into perspective the reduction in seizures and the associated costs of DS specific treatments, which should be considered from a societal perspective. Stiripentol has the lowest cost associated per NNT compared to fenfluramine and cannabidiol, strengthening its first-line position as add-on treatment to conventional antiseizures medications, when the latter are insufficient to control the convulsive seizures in DS.