Fenfluramine Treatment Beyond Dravet and Lennox-gastaut Syndromes: A Novel Use in Genetic Developmental And/or Epileptic Encephalopathies (DEEs)
Abstract number :
2.382
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2024
Submission ID :
1219
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Amy Urbina Pacheco, MS, BS, BA – Tulane University School of Medicine
Aizara Ermekbaeva, BS – Tulane University School of Medicine
Robin Varughese, MD – Northwell Health
Candice Marti, MSN, CPNP – Boston Children's Hospital
Annapurna Poduri, MD, MPH – Boston Children's Hospital
Yash Shah, MD, MPH – Our Lady of the Lake Children's Hospital
Kothare Sanjeev, MD – Northwell Health
Rationale: Fenfluramine (FFA), an amphetamine derivative, was historically used as an appetite suppressant in the 1970s but was discontinued for its association with valvular heart disease and pulmonary hypertension. FFA continued to be researched for its potential benefit in other fields such as epilepsy. Significant results in randomized trials led to FDA approval for usage of FFA in children aged two years and older with Dravet syndrome in 2020 and Lennox-Gastaut syndrome (LGS) in 2022. [1,2]
Considering FFA’s success in these populations, we aimed to characterize the extent of its efficacy related to refractory epilepsy in individuals with genetic developmental and/or epileptic encephalopathies (DEEs). We hypothesized similar rates of improvement (at least 25% seizure reduction) as the LGS and Dravet syndrome studies.
Methods: After Institutional Review Board approval, a systematic retrospective chart review was conducted of pediatric patients with DEE receiving clinical care in the Boston Children’s Hospital, Northwell Health, and Our Lady of the Lake Children’s Hospital-Baton Rouge systems who were placed on FFA after July 1, 2020. Self-reported seizure frequency and side effects were extracted. Reduction in monthly seizure frequency was the primary outcome investigated. T-test was performed to evaluate mean difference in seizure frequency pre-and-post-fenfluramine treatment.
Results:
There were 20 seizure patients of diverse etiologies who were placed on FFA and met our inclusion criteria. Patients were on an average of 3.5 antiseizure medications (ASMs) alongside fenfluramine and exhibited an average of 3 seizure types.
A statistically significant (p=0.008) decrease in seizure frequency in days per month was found, with a mean reduction of 4.6 days per month. Some patients responded more dramatically than others with 95% seizure reduction in patients with apneic seizures and tuberous sclerosis (n=2). 7 (35%) patients achieved 50% seizure freedom and 6 (30%) achieved 75% seizure freedom.
Conclusions: This retrospective report suggests that FFA may be an effective add-on therapeutic option in patients with rare, genetic epilepsies where efficacy was notable early on in drug initiation and titration. A trial of FFA for refractory seizures may be considered to assess efficacy in the DEE population beyond Dravet and Lennox-Gastaut syndromes.
Funding: N/A
Anti-seizure Medications