Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth.

• Appetite disturbances and growth abnormalities are common in Dravet syndrome (DS). • Fenfluramine reduces seizure frequency in DS and has known effects on appetite. • After ≥12 months or ≥24 months of fenfluramine treatment in children with DS: • Impact on growth was minimal as measured by Z -score analysis. • Weight gain and height were comparable to growth curves in historical controls with DS. Appetite disturbance and growth abnormalities are commonly reported in children with Dravet syndrome (DS). Fenfluramine (Fintepla) has demonstrated profound reduction in convulsive seizure frequency in DS and was recently approved for use in DS in the US and EU. Prior to its use in epilepsy, fenfluramine was approved to suppress appetite in obese adults. Here, we evaluated the impact of fenfluramine on weight and growth in patients with DS treated for ≥12 months or ≥24 months and compared the results with growth curves in normative reference populations and published historical controls among patients with DS. Historical control data from a recent study of 68 patients with DS show decreases in height and weight Z -scores of ∼0.1 standard deviation (SD) for every 12-month increase in age (Eschbach K. Seizure. 2017;52:117–22). Anthropometric data for fenfluramine were extracted from an open-label extension (OLE) study of eligible patients with DS (2–18 y/o; fenfluramine dose: 0.2–0.7 mg/kg/day). Z -score analyses were based on the Boston Children's Hospital algorithm and assessed potential impact of fenfluramine on growth at OLE baseline, at Month 12, and at Month 24. A mixed-effect model for repeated measures (MMRM) estimated changes in height and weight over time. Height and weight Z -scores were also analyzed by dose group (0.2–<0.3 mg/kg/day, 0.3–<0.5 mg/kg/day, and 0.5–0.7 mg/kg/day), averaged over time. At the time of analysis, 279 patients were treated with fenfluramine for ≥12 months; 128 were treated for ≥24 months. Relative to the reference population with DS, fenfluramine treatment for ≥12 months or for ≥24 months had minimal impact on height or weight over time as assessed by Z -score analyses. No substantial dose-dependent changes from baseline were observed at Month 12 nor at Month 24. MMRM showed that patients treated with fenfluramine for ≥12 months (N = 262) had an estimated change in Z -score per year of −0.056 for height and −0.166 for weight. For patients with data from all three time points (baseline, 12 months, and 24 months; N = 110), estimated changes in Z -scores per year were −0.025 for height and −0.188 for weight. MMRM projections based on normative reference growth curves were comparable to growth data from historical control populations with DS. Long-term treatment with fenfluramine had minimal impact on the growth of patients with DS as demonstrated by differences in Z -scores for height and weight at 12 months and at 24 months. Changes in Z -scores for height and weight were consistent with published reports on patients with DS. [ABSTRACT FROM AUTHOR]