Fenfluramine Use in Developmental and Epileptic Encephalopathies Beyond Dravet and Lennox-gastaut Syndrome
Abstract number :
1.326
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2024
Submission ID :
1371
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Víctor Soto Insuga, PhD – Hospital Universitario Niño Jesus
Elena Gonzalez-Alguacil, MD – Hospital Universitario Niño Jesus
Juan Jose García Peñas, MD – Hospital San Rafael, Madrid
Nuria Lamagrande Casanova, MD – Hospital Universitario Niño Jesus
Anna Duat, MD PhD – Hospital Infantil Universitario Niño Jesús
Virginia Navarro, MD – Hospital Burgos
David Conejo, PhD – Hospital Burgos
Rationale:
Fenfluramine (FFA) is an antiseizure medication (ASM) indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), although it is probably also effective in other types of epilepsies. Its mechanism of action is multimodal and novel, acting as a specific agonist of the serotonin and sigma-1 receptors of the central nervous system
Methods:
Retrospective study by review of medical records in two tertiary hospitals to evaluate efficacy and safety of FFA in the treatment of seizures beyond Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).
Results:
Forty-two children were studied, 70% boys, with a mean age at onset of FFA of 10.2 years [1-17 years]. The onset of epilepsy was before the age of 2 years in 70%, with a mean of 8.2 years of evolution before the onset of FFA and a mean of 9 previous anti-crisis drugs (ACDs) [3-17 ACDs]. The mean number of associated FACs received a mean of 3.2 concomitant FACs [1-5]. The target dose ranged from 0.3 mg/kg/day to 0.7 mg/kg/day, with dose escalation being slower than recomended titration in most cases (81%).
FFA was used in 19 patients with SLG (45%), 14 patients with DS (33%) and 9 patients off-label indication (OFF) (21%). The overall responder rate of >50% of seizures was 65% (reduction >90% in 18%). The most responsive group was the DS-group; 75% of patients with seizure reduction greater than 90%. Efficacy in the SLG and OFF-group was similar.
Within the OFF-group, all patients had epileptic and neurodevelopmental encephalopathies; according to etiology: 6 genetic (identified in 6 of them: CDKL5, SCN1B, STXBP1, SCN1A-GOF, NEXMIF, 19q11.2 microdeletion), 2 structural (hypoxic-ischemic and 1 herpes-virus encephalitis after anti-NMDA) and 1 unidentified. Overall responder rate in this group was 4/9 (44%) and according to seizure type: tonic (3/6), focal (2/4), absent (1/3), myoclonic (1/4) and spasms (0/1).
Thirty-nine percent of our patients presented some adverse effect (AE) with the use of FFA. In most cases these were mild AE's, leading to drug withdrawal in only 7% of patients. The most frequent adverse effect was somnolence (26%), followed by anorexia (9%) and irritability (9%). There were no differences with respect to safety in the three groups.
Following the clinical impression scale (CGI) there was improvement according to the investigator in cognition 79%; behavior 70%; sleep 33%; epilepsy 65%; and globally according to the caregiver 65%.
Conclusions:
FFA could be a safe and effective adjuvant treatment in patients with developmental and epileptic encephalopathies beyond SLG and SD.
Funding:
Authors have not received any funds
Clinical Epilepsy