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Publications

Journal Article Ahead of print 3 citations

PubMed: 42334048 DOI: 10.1002/epi.70342

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

Epilepsia

Authors: Vicente Villanueva, Elena González-Alguacil, Patricia Smeyers, Sara Hernández, Victor Soto-Insuga, Alejandro Fernández-Cabrera, Laura Olivié, Teresa de Santos, Beatriz Parejo, Lucas Iacampo, Belén Ortuño, Javier Aparicio, Montserrat Fuentes, Juan Rodriguez-Uranga, Paula Martínez-Agredano, José Carlos Estévez, Angel Aledo-Serrano, Rocio Martin-Alvarez, David Conejo, Belen Baena, Blanca Mercedes-Álvarez, Yolanda López, Alba Sierra-Marcos, Rocio Trincado-Lamuño, Mouna Ennazeh, Jesús González de la Aleja, Julia Renau, Maria Dolores Castro-Vilanova, Fátima Romero-Aguilera, José M Serratosa

Affiliations

  • Hospital Universitario y Politécnico La Fe, Member of ERN Epicare, Valencia, Spain.
  • Hospital Universitario Niño Jesús, Madrid, Spain.
  • Hospital Universitario Lucus Augusti, Lugo, Spain.
  • Hospital Universitario Fundación Jiménez Diaz, Madrid, Spain.
  • Hospital Universitario Clinico San Carlos, Madrid, Spain.
  • Hospital Universitario de Canarias, Santa Cruz de tenerife, Spain.
  • Hospital Universitario Sant Joan de Déu, Barcelona, Spain.
  • Hospital de Mérida, Mérida, Spain.
  • Centro Neurologia Avanzada, Sevilla, Spain.
  • Hospital Universitario Reina Sofia, Córdoba, Spain.
  • Hospital Blua Sanitas Valdebebas, Madrid, Spain.
  • Hospital Universitario de Burgos, Burgos, Spain.
  • Hospital Universitario Gregorio Marañón, Madrid, Spain.
  • Hospital Universitario Regional de Málaga, Málaga, Spain.
  • Hospital Universitario Santa Creu i Sant Pau, Institut de Recerca Sant Pau, Barcelona, Spain.
  • Hospital Universitario 12 de Octubre, Madrid, Spain.
  • Hospital General Universitario Castellón, Castellón, Spain.
  • Hospital Universitario Alvaro Cunqueiro, Vigo, Spain.
  • Spanish Epilepsy Society, Madrid, Spain.

Abstract

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.

MeSH

Epilepsy, Anticonvulsants, Fenfluramine, Seizures, Therapeutics, Dravet Syndrome