Impact of Fenfluramine on the Expected SUDEP Incidence Rate in Patients with Dravet Syndrome

Background/Purpose: Sudden unexpected death in epilepsy (SUDEP) is a sudden death in epilepsy patients not explained by status epilepticus, trauma, or any another known cause. In Dravet syndrome (DS) the incidence of SUDEP is about 6-fold higher than in other forms of epilepsy. The objective of this study was to compare the incidence of SUDEP in FFA-treated DS patients with literature reports of SUDEP incidence in patients with DS receiving anticonvulsive treatment without FFA.

Methods: For the study group without FFA, publications were identified in PubMed searching “Dravet [title] AND (mortality OR death OR SUDEP).” The FFA-treated population comprised patients from 3 sources: international phase 3 clinical trials, US and European Early Access Programs (EAPs), and a long-term, open-label study spanning 32 years. The incidence of SUDEP was expressed as deaths per 1,000 person-years of observation.

Results: Nine studies describing the incidence of SUDEP in DS were identified. Cooper (Cooper MS, Epilepsy Res 2016;128:43–47) was considered the most rigorous, reporting a SUDEP rate of 9.32 per 1000 person-years (98% CI, 4.46–19.45). 732 patients treated with fenfluramine provided 1185.3 person-years. The FFA-SUDEP rate was below the lower limit of 98% CI reported by Cooper, whereas the SUDEP rate before starting FFA was similar to the literature numbers.

Conclusion: Results show a lower incidence of SUDEP and all-cause mortality in the FFA-treated population compared to patients without FFA of the literature. Further research is warranted to clarify influencing factors on SUDEP to reduce its risks.

The data were first presented at AES 2020 (Virtual 74th American Epilepsy Society Annual Meeting).

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
28 October 2021