Cross, JH;
Galer, BS;
Gil-Nagel, A;
Devinsky, O;
Ceulemans, B;
Lagae, L;
Schoonjans, A-S;
... Gammaitoni, AR; + view all
(2021)
Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome.
Seizure
, 93
pp. 154-159.
10.1016/j.seizure.2021.10.024.
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Abstract
PURPOSE: To assess the impact of fenfluramine (FFA) on the expected mortality incidence, including sudden unexpected death in epilepsy (SUDEP), in persons with Dravet syndrome (DS). METHODS: In this pooled analysis, total time of exposure for persons with DS who were treated with FFA in phase 3 clinical trials, in United States and European Early Access Programs, and in two long-term open-label observational studies in Belgium was calculated. Literature was searched for reports of SUDEP mortality in DS, which were utilized as a comparison. Mortality rates were expressed per 1000 person-years. RESULTS: A total of 732 persons with DS were treated with FFA, representing a total of 1185.3 person-years of exposure. Three deaths occurred, all in the phase 3 program: one during placebo treatment (probable SUDEP) and two during treatment with FFA (one probable SUDEP and one definite SUDEP). The all-cause and SUDEP mortality rates during treatment with FFA was 1.7 per 1000 person-years (95% CI, 0.4 to 6.7), a value lower than the all-cause estimate of 15.8 per 1000 person-years (95% CI, 9.9 to 25.4) and SUDEP estimate of 9.3 (95% CI, 5.0 to 17.3) reported by Cooper et al. (Epilepsy Res 2016;128:43-7) for persons with DS receiving standard-of-care. CONCLUSION: All-cause and SUDEP mortality rates in DS patients treated with FFA were substantially lower than in literature reports. Further studies are warranted to confirm that FFA reduces SUDEP risk in DS patients and to better understand the potential mechanism(s) by which FFA lowers SUDEP risk. CLINICAL TRIAL REGISTRATION: NCT02926898, NCT02682927, NCT02826863, NCT02823145, NCT03780127.
| Type: | Article |
|---|---|
| Title: | Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.seizure.2021.10.024 |
| Publisher version: | https://doi.org/10.1016/j.seizure.2021.10.024 |
| Language: | English |
| Additional information: | © 2021 The Authors. Published by Elsevier Ltd on behalf of British Epilepsy Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Dravet syndrome, Fenfluramine, Mortality, SUDEP |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10139512 |
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