{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:42:23Z","timestamp":1792226543223,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006978","name":"University of California Berkeley","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006978","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Long\u2010term safety and global functioning are reported in patients with Dravet syndrome (DS) or Lennox\u2013Gastaut syndrome (LGS) treated with fenfluramine in an open\u2010label extension (OLE) study after participating in a previous open\u2010label feeder study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients could enroll in this international, multicenter OLE (NCT03936777) after completing one of three fenfluramine open\u2010label studies. The latest feeder study fenfluramine dose was continued, then flexibly titrated (maximum: .7\u2009mg\/kg\/day [26\u2009mg\/day] without stiripentol or .4\u2009mg\/kg\/day [17\u2009mg\/day] with stiripentol), with \u22651 concomitant antiseizure medication administered. Primary endpoint was fenfluramine long\u2010term safety\/tolerability. Global functioning using caregiver\u2010 and investigator\u2010reported Clinical Global Impression of Improvement (CGI\u2013I) ratings, globally and for subdomains (cognition, behavior, motor function), at last visit relative to study baseline was evaluated. Overall treatment exposure and age groups were analyzed post hoc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 412 patients enrolled (DS: 265 [64.3%], LGS: 147 [35.7%]); 30.8% were \u226518\u2009years old. Median fenfluramine treatment duration in this OLE was 729.5\u2009days (range\u2009=\u20098\u20131544), and overall median fenfluramine exposure, including feeder studies, was 1464.5\u2009days (range\u2009=\u2009171\u20132800). In this OLE, \u22651 treatment\u2010emergent adverse event (TEAE) was reported in 311 (75.5%) patients; fenfluramine\u2010related (per investigator) serious TEAEs were reported in five (1.2%) patients. Three patients died in this OLE (deemed unrelated to fenfluramine by investigators). After starting this OLE already receiving fenfluramine, 373 of 401 (93.0%) and 376 of 401 (93.8%) patients were rated by caregiver and investigator, respectively, as \u201cimproved or no change\u201d on CGI\u2013I versus this study baseline; subdomain ratings of \u201cimproved or no change\u201d were largely consistent with global assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>In our OLE study of patients with DS or LGS treated with fenfluramine (up to 4\u2009years), no new or unexpected safety signals were observed; global functioning was improved or stable (vs. study baseline) in &gt;90% of patients, supporting long\u2010term fenfluramine use in pediatric and adult patients with DS or LGS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70371","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T11:07:19Z","timestamp":1783163239000},"page":"5227-5242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prolonged fenfluramine use in open\u2010label studies of Dravet or Lennox\u2013Gastaut syndromes: Long\u2010term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness"],"prefix":"10.1002","volume":"67","author":[{"given":"Antonio","family":"Gil\u2010Nagel","sequence":"first","affiliation":[{"name":"Hospital Ruber Internacional  Madrid Spain"}],"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 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