{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:38:12Z","timestamp":1793205492218,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,10]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n To assess the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) stratified by age, number of previously attempted antiseizure medications (ASMs), and\n SCN1A<\/jats:italic>\n pathogenic variant status.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this post hoc analysis, data from three randomized controlled trials (RCTs) in patients with DS (2\u201318\u2009years) were pooled and stratified by age (<4; \u22654\u2009years), number of previous ASMs (1\u20133; 4\u20136; \u22657), and\n SCN1A<\/jats:italic>\n pathogenic variant status (\n SCN1A<\/jats:italic>\n +;\n SCN1A<\/jats:italic>\n \u2212). Stratified groups were assessed and compared with the pooled placebo group (change in monthly convulsive seizure frequency [MCSF], longest convulsive seizure\u2010free interval, and Clinical Global Impression\u2013Improvement [CGI\u2013I] scale scores rated by parents\/caregivers and investigators), and safety (treatment\u2010emergent adverse events [TEAEs]: frequency, days to onset, and proportion resolved).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 348 patients included in the RCTs, 216 were randomized to fenfluramine (0.7\u2009mg\/kg\/day,\n n<\/jats:italic>\n \u2009=\u200988; 0.4\u2009mg\/kg\/day [with stiripentol],\n n<\/jats:italic>\n \u2009=\u200943; 0.2\u2009mg\/kg\/day,\n n<\/jats:italic>\n \u2009=\u200985) and 132 to placebo. Compared with placebo, fenfluramine treatment (all doses combined) resulted in greater MCSF reductions, greater increases in longest convulsive seizure\u2010free intervals, and a higher proportion of parents\/caregivers and investigators reporting clinically meaningful improvement (\u201cMuch Improved\u201d, \u201cVery Much Improved\u201d) on CGI\u2013I scores across all stratified groups. CGI\u2013I scores were consistent across fenfluramine doses in most stratified groups, but patients with the fewest number of previous ASMs had the greatest frequency of clinically meaningful improvement on investigator\u2010rated CGI\u2013I scores. Safety outcomes were similar across all strata. Most TEAEs resolved by end\u2010of\u2010study.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n Fenfluramine treatment was associated with improved seizure outcomes and global functioning compared with placebo regardless of age, number of previous ASMs, and\n SCN1A<\/jats:italic>\n status in patients with DS. Fenfluramine was well\u2010tolerated; no new safety signals were identified. Further studies with larger sample sizes (including adults) and a priori inferential analyses of stratified groups are warranted.\n <\/jats:p>\n <\/jats:sec>\n \n Plain Language Summary<\/jats:title>\n \n Patients with Dravet syndrome struggle with seizures and everyday life. In three studies, patients aged 2\u201318\u2009years received fenfluramine or placebo (sugar pill). Fenfluramine lowered seizures without many side effects. Researchers combined results from these studies to see how fenfluramine worked in different patient groups based on age, number of previous medications, and a gene called\n SCN1A<\/jats:italic>\n . They looked at seizure reduction and whether doctors felt patients had improved. In all groups, fenfluramine worked better than placebo, with similar side effects. Researchers believe fenfluramine helped these patients, but some groups were small, so these results need to be confirmed.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi4.70340","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T16:26:05Z","timestamp":1787415965000},"page":"1692-1705","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of fenfluramine in Dravet syndrome: The impact of patient clinical characteristics"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-4074","authenticated-orcid":false,"given":"Rima","family":"Nabbout","sequence":"first","affiliation":[{"name":"Reference Centre for Rare Epilepsies H\u00f4pital Universitaire Necker\u2010Enfants Malades, AP\u2010HP, Member of the European Reference Network (ERN) EpiCARE Paris France"},{"name":"Institut Imagine, INSERM 1163 Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2081-8988","authenticated-orcid":false,"given":"Joseph","family":"Sullivan","sequence":"additional","affiliation":[{"name":"University of California San Francisco Weill Institute for Neurosciences, Benioff Children's Hospital San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-9749","authenticated-orcid":false,"given":"St\u00e9phane","family":"Auvin","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Reference Center for Rare Epilepsies, Member of ERN EpiCARE H\u00f4pital Universitaire Robert Debr\u00e9 Paris France"},{"name":"Institut Hospitalo\u2010Universitaire Robert\u2010Debr\u00e9 du Cerveau de l'Enfant Paris France"},{"name":"INSERM NeuroDiderot Universit\u00e9 Paris\u2010Cit\u00e9 Paris France"},{"name":"Institut Universitaire de France (IUF) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-4829","authenticated-orcid":false,"given":"J. Helen","family":"Cross","sequence":"additional","affiliation":[{"name":"UCL NIHR BRC Great Ormond Street Institute of Child Health London UK"},{"name":"Great Ormond Street Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center NYU Langone Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-0793","authenticated-orcid":false,"given":"Antonio","family":"Gil\u2010Nagel","sequence":"additional","affiliation":[{"name":"Hospital Ruber Internacional Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Meyer Children's Hospital IRCCS & University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-0827","authenticated-orcid":false,"given":"Kelly G.","family":"Knupp","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-846X","authenticated-orcid":false,"given":"M. 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