{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:19:10Z","timestamp":1792513150628,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011110","name":"UCB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We analyzed the long\u2010term safety and effectiveness of fenfluramine (FFA) in patients with Dravet syndrome (DS) in an open\u2010label extension (OLE) study after participating in randomized controlled trials (RCTs) or commencing FFA de novo as adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with DS who participated in one of three RCTs or were 19 to 35\u2009years of age and started FFA de novo were included. Key endpoints were: incidence of treatment\u2010emergent adverse events (TEAEs) in the safety population, and median percentage change in monthly convulsive seizure frequency (MCSF) from the RCT baseline to end of study (EOS) in the modified intent\u2010to\u2010treat (mITT) population. Post hoc analyses compared effectiveness in patients on concomitant stiripentol (STP) vs those not taking STP, and assessed safety (TEAEs) and effectiveness (Clinical Global Impression\u2010Improvement [CGI\u2010I] scale ratings) in patients enrolled as adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 374 patients, including 45 adults, received \u22651 FFA dose. Median FFA exposure was 824\u2009days (range, 7\u20131280). TEAEs occurring in \u226510% of patients were pyrexia, nasopharyngitis, decreased appetite, seizure, decreased blood glucose, diarrhea, abnormal echocardiography (only physiologic regurgitation), upper respiratory tract infection, influenza, vomiting, and ear infection; no valvular heart disease or pulmonary arterial hypertension was observed over the OLE. In the mITT population (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009324), median percentage change in MCSF from baseline to EOS was \u221266.8% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001). The post hoc analyses of MCSF change from baseline to EOS in patients on concomitant STP (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200975) was \u221236.2% vs \u221271.6% in those not on concomitant STP (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009234) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001). In adult patients, 29 of 41 (70.7%) and 29 of 42 patients (69.1%) demonstrated clinically meaningful improvement on CGI\u2010I at last visit as rated by caregivers and investigators, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our OLE study of FFA in patients with DS confirmed previous positive findings and extended the exposure up to 3.5\u2009years. No new or unexpected safety signals were observed and FFA demonstrated sustained and clinically meaningful reduction in MCSF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18342","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:40:07Z","timestamp":1741779607000},"page":"1919-1932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Long\u2010term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"first","affiliation":[{"name":"Austin Hospital and Royal Children's Hospital, Florey and Murdoch Children's Research Institutes, University of Melbourne  Melbourne Victoria 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C.","family":"Wirrell","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-7312","authenticated-orcid":false,"given":"Tilman","family":"Polster","sequence":"additional","affiliation":[{"name":"Krankenhaus Mara\u2014Bethel Epilepsy Centre, Medical School OWL Bielefeld University  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-0287","authenticated-orcid":false,"given":"Nicola","family":"Specchio","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital IRCCS  Rome Italy"},{"name":"Member of the European Reference Network EpiCARE University Hospitals KU  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milka","family":"Pringsheim","sequence":"additional","affiliation":[{"name":"Sch\u00f6n Klinik Vogtareuth  Vogtareuth 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