title: Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine.
abstract: Dravet syndrome (DS) is a rare and therapy-resistant epilepsy syndrome. A retrospective analysis of add-on fenfluramine treatment in 12 patients with DS was published in 2012 and provided evidence of a meaningful long-term response. Herein we present the results of a subsequent 5-year prospective observation of this original cohort. Ten patients with a mean current age of 24 years were followed prospectively from 2010 until 2014. The mean current dose of fenfluramine was 0.27 mg/kg/day, with a mean treatment duration of 16.1 years. Seizure frequency was derived from a seizure diary. Cardiac examinations and assessments of clinical effectiveness and adverse events were performed at least annually. Three patients were seizure-free for the entire 5 years, and an additional four patients experienced seizure-free intervals of at least 2 years. Fenfluramine was generally well-tolerated. Two patients had mild (stable) valve thickening on the last echocardiography that was deemed clinically insignificant. No patient had any clinical or echocardiographic signs of pulmonary hypertension. These findings support the long-term control of convulsive seizures by low-dose fenfluramine while being well tolerated in this cohort of patients with DS. After up to 27 years of treatment, no patient has developed any clinical signs or symptoms of cardiac valvulopathy or pulmonary hypertension.
authors.affiliation: Department of Neurology-Pediatric Neurology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.affiliation: Department of Neurology-Pediatric Neurology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: Schoonjans
authors.affiliation: Department of Pediatric Cardiology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Marchau
authors.affiliation: Department of Cardiology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Paelinck
authors.affiliation: Department of Development and Regeneration, Section Pediatric Neurology, University Hospitals Gasthuisberg, Leuven, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004831:Epilepsies, Myoclonic / Q000188:drug therapy*; D005260:Female; D005277:Fenfluramine / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005277:Fenfluramine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Dravet syndrome; FFA; Fenfluramine; Orphan drugs; SCN1A