Effectiveness and tolerability of fenfluramine in pediatric and adult patients with developmental and epileptic encephalopathies: A multicenter, retrospective, real-world clinical-practice study.

OBJECTIVE

Developmental and epileptic encephalopathies (DEEs) are characterized by drug-resistant seizures and developmental slowing/regression. We examined the efficacy and tolerability of fenfluramine (FFA) in pediatric and adult patients with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and other DEEs.

METHODS

In this multicenter, retrospective, real-world study, FFA treatment was initiated ≥12 months before database closure. Data from patients' charts at 3, 6 and 12 months were recorded in the Spanish Epilepsy Society's DEEs registry. Effectiveness endpoints included seizure reductions of 100%, ≥75%, and ≥50% (responder), median percent seizure reduction, and seizure worsening. Safety endpoints included adverse event (AE) rates.

RESULTS

The study included 166 patients (LGS, n = 84; DS, n = 42; other DEE, n = 40; mean age 16.6 ± 12.1 years [111 pediatric, median 10.1 years; 55 adult, median 26.5 years]). Patients had a median of 3 prior failed anti-seizure medications (ASMs). At 12 months, the median FFA dose was 0.49 mg/kg/day, with 77.1% treatment retention. There was a 68.8% median reduction in seizure frequency between baseline and 12 months (p < .001), with significant reductions across all diagnostic groups (LGS, p < .001; DS, p < .001; other DEE, p = .004). The 12-month ≥50% responder rate was 61%, with no statistically significant differences according to age. At 12 months, there were significant reductions in the mean number of concomitant ASMs (p = .004) and the proportion of patients requiring rescue medication (p < .001). Meaningful improvements in Clinical Global Impression scores for cognition (59.3% of patients), behavior (40.9%), sleep (24.3%), and caregiver (44.8%) domains were observed. At 12 months, AEs were reported in 68.1% of patients (mostly mild-to-moderate) and AEs leading to discontinuation in 12%, with no significant differences according to age.

SIGNIFICANCE: FFA was effective, with predictable tolerability, in patients with different DEEs and seizure types, supporting its use as an effective treatment option in pediatric and adult patients with DEEs.