Real-World Use of Fenfluramine for Dravet Syndrome: a Retrospective Cohort Study Using a National Pharmacy Database
Samden Lhatoo1, Wesley Kerr2, Elaine Wirrell3, Elizabeth Donner4, Joseph Sullivan5, Renzo Guerrini6, Ingrid Scheffer7, Sylvain Rheims8, J Helen Cross9, Lieven Lagae10, Philippe Ryvlin11, Antonio Gil-Nagel12, Jeffrey Noebels13, Jenna Roberts14, Amélie Lothe14, Milena Tryfon14, Michael Rañopa14, Orrin Devinsky15
1University of Texas Houston Health Sciences Center, 2University of Pittsburgh, 3Mayo Clinic/Dept of Child Neurology, 4The Hospital for Sick Children, University of Toronto, 5University of California San Francisco Weill Institute for Neurosciences, Benioff Children’s Hospital, 6Anna Meyer Children's Hospital, University of Florence, 7University of Melbourne, Austin Hospital and Royal Children's Hospital, Florey and Murdoch Children’s Research Institutes, 8Hospices Civils de Lyon and Lyon 1 University, 9UCL NIHR BRC Great Ormond Street Institute of Child Health, Great Ormond Street Hospital, 10Member of the European Reference Network EpiCARE, University of Leuven, 11University of Lausanne, 12Hospital Ruber Internacional, 13Baylor College of Medicine, 14UCB, 15NYU Langone Medical Center
Objective:
This study describes mortality rates and real-world use of fenfluramine (FFA) in United States (US) patients with Dravet syndrome (DS) who were new FFA users, obtained from a single specialty pharmacy.
Background:
Patients with DS are at risk of premature mortality, with all-cause mortality rates previously reported as 8.6-15.8/1000 person-years (Cooper Epilepsy Res 2016; Donnan Neurology 2023). In the US, FFA is approved for managing seizures in patients ≥2 years old with DS. A prior post-hoc analysis of FFA studies demonstrated lower all-cause mortality rates in FFA-treated patients compared to expected rates (Cross Seizure 2021).
Design/Methods:
This retrospective study evaluated patients with DS who were new FFA users and received their first shipment ≥6 months prior to the data cut. Outcomes include demographics, FFA doses, persistence rates by index year, and mortality rates. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) for 2021-2023 were reported. Descriptive statistics were used.
Results:
From 07/01/2020 to 3/15/2024, 1043 patients with DS were new FFA users; 49.2% were 6-17 years old, 56.6% were prescribed FFA by pediatric epileptologists, and 56.0% had previously taken cannabidiol. Initial median FFA dose was 0.3 mg/kg/day (range: 0.1-1.1 mg/kg/day) and median maintenance dose was 0.5 mg/kg/day (range: 0.02-1.4 mg/kg/day). Persistence rates at 6 and 12 months, respectively, were: 90.9% and 78.5% in 2020, 85.8% and 76.9% in 2021, 83.5% and 74.8% in 2022. Median treatment duration was 21.3 months; 729 patients continued on FFA at data cut. There were 16 deaths over 1865 patient-years, resulting in an estimated mortality rate of 8.6/1000 person-years (95% CI: 5.6-11.6); SMR from 2021-2023 was 2.0 (95% CI: 1.1-3.3).
Conclusions:
This real-world analysis revealed that mortality rates in patients with DS treated with FFA were similar to previous studies and demonstrated an encouraging SMR. Further studies will evaluate causes of death, including sudden unexpected death in epilepsy.
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