PMID- 35801621
OWN - NLM
STAT- MEDLINE
DCOM- 20221202
LR  - 20221229
IS  - 2470-9239 (Electronic)
IS  - 2470-9239 (Linking)
VI  - 7
IP  - 4
DP  - 2022 Dec
TI  - An examination of the efficacy and safety of fenfluramine in adults, children, 
      and adolescents with Dravet syndrome in a real-world practice setting: A report 
      from the Fenfluramine European Early Access Program.
PG  - 578-587
LID - 10.1002/epi4.12624 [doi]
AB  - OBJECTIVE: To examine the efficacy and safety of fenfluramine in patients with 
      Dravet syndrome (DS) in three age groups: <6, 6-17, and >/=18 years old, treated in 
      a real-world setting. METHODS: Patients with DS were treated with fenfluramine in 
      the European Union Early Access Program (EAP). Following a 28-day baseline period 
      to establish the pretreatment monthly convulsive seizure frequency (MCSF), 
      fenfluramine was started at a dose chosen by the treating physician and gradually 
      titrated based on efficacy and tolerability up to a maximum of 0.7 mg/kg/day. 
      Seizure incidence was recorded in a written diary, and adverse events (AEs) were 
      reported at each patient visit. Cardiovascular safety was assessed by 
      transthoracic echocardiography before treatment started and at least every 
      6 months thereafter. RESULTS: A total of 149 patients have enrolled in the EAP 
      and 63 were <6 years old, 62 were 6-17 years old, and 24 were >/=18 years old. 
      After 3 months of treatment 62%, 53%, and 50% of patients demonstrated >/=75% 
      reduction in MCSF in the <6, 6-17, and >/=18-year-old groups, respectively. This 
      pattern of response was sustained through 12 months of treatment with 55%, 46%, 
      and 80% of the <6, 6-17, and >/=18-year-old groups, respectively, experiencing a 
      >/=75% reduction in MCSF. Most common AEs were loss of appetite (21%) and 
      somnolence (16%). No valvular heart disease or pulmonary artery hypertension was 
      observed. SIGNIFICANCE: The magnitude, consistency, and durability of the 
      response to add-on fenfluramine is consistent across age groups in patients with 
      Dravet syndrome.
CI  - (c) 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf 
      of International League Against Epilepsy.
FAU - Guerrini, Renzo
AU  - Guerrini R
AUID- ORCID: 0000-0002-7272-7079
AD  - Children's Hospital A Meyer, University of Florence, Full Member of European 
      Reference Network on Rare and Complex Epilepsies EpiCARE, Florence, Italy.
FAU - Specchio, Nicola
AU  - Specchio N
AUID- ORCID: 0000-0002-8120-0287
AD  - Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu 
      Children's Hospital IRCCS, Full Member of European Reference Network on Rare and 
      Complex Epilepsies EpiCARE, Rome, Italy.
FAU - Aledo-Serrano, Angel
AU  - Aledo-Serrano A
AUID- ORCID: 0000-0003-4889-3365
AD  - Epilepsy Program, Department of Neurology, Hospital Ruber Internacional, Madrid, 
      Spain.
FAU - Pringsheim, Milka
AU  - Pringsheim M
AD  - Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children 
      and Adolescents, Schon Klinik, Vogtareuth, Germany.
AD  - Department for Congenital Heart Disease and Pediatric Cardiology, German Heart 
      Center, Munich, Germany.
AD  - Research Institute for Rehabilitation, Transition and Palliation, Paracelsus 
      Medical University, Salzburg, Austria.
FAU - Darra, Francesca
AU  - Darra F
AD  - Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and 
      Pediatrics, University of Verona, Full Member of European Reference Network on 
      Rare and Complex Epilepsies EpiCARE, Verona, Italy.
FAU - Mayer, Thomas
AU  - Mayer T
AD  - Epilepsy Center Kleinwachau, Dresden-Radeberg, Germany.
FAU - Gil-Nagel, Antonio
AU  - Gil-Nagel A
AD  - Epilepsy Program, Department of Neurology, Hospital Ruber Internacional, Madrid, 
      Spain.
FAU - Polster, Tilman
AU  - Polster T
AUID- ORCID: 0000-0002-9531-7312
AD  - Krankenhaus Mara - Bethel Epilepsy Centre, Department of Epileptology, Medical 
      School, Bielefeld University, Bielefeld, Germany.
FAU - Zuberi, Sameer M
AU  - Zuberi SM
AD  - Paediatric Neurosciences Research Group, Royal Hospital for Children & Institute 
      of Health & Wellbeing, University of Glasgow, Glasgow, UK.
FAU - Lothe, Amelie
AU  - Lothe A
AD  - Zogenix International, Maidenhead, UK.
FAU - Gammaitoni, Arnold
AU  - Gammaitoni A
AUID- ORCID: 0000-0002-4775-2862
AD  - Zogenix, Inc., Emeryville, California, USA.
FAU - Strzelczyk, Adam
AU  - Strzelczyk A
AUID- ORCID: 0000-0001-6288-9915
AD  - Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, 
      Goethe-University Frankfurt, Frankfurt am Main, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220808
PL  - United States
TA  - Epilepsia Open
JT  - Epilepsia open
JID - 101692036
RN  - 2DS058H2CF (Fenfluramine)
RN  - 0 (Anticonvulsants)
RN  - CDKL5 deficiency disorder
SB  - IM
MH  - Child
MH  - Adult
MH  - Humans
MH  - Adolescent
MH  - *Fenfluramine/adverse effects
MH  - Anticonvulsants/therapeutic use
MH  - Treatment Outcome
MH  - *Epilepsies, Myoclonic/drug therapy
MH  - Seizures/drug therapy
PMC - PMC9712464
OTO - NOTNLM
OT  - Dravet syndrome
OT  - clinical practice
OT  - fenfluramine
OT  - refractory epilepsy
OT  - seizures
COIS- RG reports research grants from Zogenix during conduct of the submitted work; 
      speaking/consulting for Zogenix outside the submitted work; being an investigator 
      for studies with Biocodex, UCB, Angelini, and Eisai Inc.; and serving on 
      speaker/advisory boards for Biocodex, Novartis, BioMarin, and GW Pharma outside 
      the submitted work. NS has served on scientific advisory boards for Zogenix, GW 
      Pharma, BioMarin, Arvelle, Marinus, and Takeda; has received speaker honoraria 
      from Zogenix, Eisai, BioMarin, Livanova, and Sanofi; and has served as an 
      investigator for Zogenix, Marinus, BioMarin, UCB, and Roche. AA-S received 
      funding for research and educational activities from Zogenix, GW, UCB, Bial, 
      Eisai, Sanofi, Neuraxpharm, and Arvelle. MP reports a research grant from 
      Zogenix, Inc. FD reports research funding from Zogenix. TM reports research 
      funding from Bial, Eisai, GW Pharma, UCB Pharma, and Zogenix. AG-N reports 
      personal fees or research grants from Arvelle Therapeutics, Bial, Biocodex, 
      Eisai, Esteve, GW Pharma, PTC Therapeutics, Sanofi, Stoke, UCB, and Zogenix. TP 
      reports research funding from Zogenix; and consulting and speaking for Desitin, 
      Shire, Novartis, UCB Pharma, and Zogenix. SMZ reports research support from 
      Epilepsy Research UK, Dravet Syndrome UK, and Zogenix; consultancy, advisory, and 
      speaker support for GW Pharma, Encoded Therapeutics, Stoke Therapeutics, Eisai, 
      UCB Pharma, Jaguar Gene Therapy, Arvelle, and Zogenix. AL is an employee of, and 
      has ownership interest in, Zogenix. AGammaitoni is an employee of, and has 
      ownership interest in, Zogenix, Inc. AS reports personal fees and grants from 
      Angelini Pharma/Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW 
      Pharmaceuticals, Marinus Pharma, UCB, UNEEG medical, and Zogenix. We confirm that 
      we have read the Journal's position on issues involved in ethical publication and 
      affirm that this report is consistent with those guidelines.
EDAT- 2022/07/09 06:00
MHDA- 2022/12/03 06:00
PMCR- 2022/08/08
CRDT- 2022/07/08 06:22
PHST- 2022/04/08 00:00 [received]
PHST- 2022/07/03 00:00 [accepted]
PHST- 2022/07/09 06:00 [pubmed]
PHST- 2022/12/03 06:00 [medline]
PHST- 2022/07/08 06:22 [entrez]
PHST- 2022/08/08 00:00 [pmc-release]
AID - EPI412624 [pii]
AID - 10.1002/epi4.12624 [doi]
PST - ppublish
SO  - Epilepsia Open. 2022 Dec;7(4):578-587. doi: 10.1002/epi4.12624. Epub 2022 Aug 8.