Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real-world study

N. Specchio, N. Pietrafusa, V. Doccini, M. Trivisano, F. Darra, F. Ragona, A. Cossu, S. Spolverato, D. Battaglia, M. Quintiliani, M. Luigia Gambardella, A. Rosati, D. Mei, T. Granata, B. Dalla Bernardina, F. Vigevano, R. Guerrini

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Dravet syndrome (DS) is a drug-resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS. Methods: DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add-on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months. Results: Fifty-two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1-13.9). Forty-five (86.5%) patients completed the efficacy analysis. The median follow-up was 9.0 months (IQR = 3.2-9.5). At last follow-up visit, there was a 77.4% median reduction in convulsive seizures. Thirty-two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure-free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA. Significance: In this real-world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated. © 2020 International League Against Epilepsy
Original languageEnglish
Pages (from-to)2405-2414
Number of pages10
JournalEpilepsia
Volume61
Issue number11
DOIs
Publication statusPublished - 2020

Keywords

  • childhood epilepsy
  • convulsive seizures
  • Dravet syndrome
  • fenfluramine
  • SCN1A
  • clobazam
  • clonazepam
  • ethosuximide
  • levetiracetam
  • phenobarbital
  • stiripentol
  • topiramate
  • valproic acid
  • zonisamide
  • anticonvulsive agent
  • serotonin uptake inhibitor
  • add on therapy
  • Article
  • child
  • data analysis software
  • decreased appetite
  • Doppler echocardiography
  • drug dose increase
  • drug dose reduction
  • drug efficacy
  • female
  • follow up
  • genetic variability
  • human
  • major clinical study
  • male
  • multicenter study
  • open study
  • priority journal
  • prospective study
  • school child
  • seizure
  • severe myoclonic epilepsy in infancy
  • treatment response
  • unspecified side effect
  • adolescent
  • adult
  • anorexia
  • clinical trial
  • diagnostic imaging
  • myoclonus epilepsy
  • pathophysiology
  • preschool child
  • treatment outcome
  • young adult
  • Adolescent
  • Adult
  • Anorexia
  • Anticonvulsants
  • Child
  • Child, Preschool
  • Epilepsies, Myoclonic
  • Female
  • Fenfluramine
  • Follow-Up Studies
  • Humans
  • Male
  • Prospective Studies
  • Seizures
  • Serotonin Uptake Inhibitors
  • Treatment Outcome
  • Young Adult

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