{"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":1793205492131,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"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":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      In the phase 3 randomized controlled trial (RCT; NCT03355209) of fenfluramine in Lennox\u2013Gastaut syndrome (LGS), patients in fenfluramine treatment groups (0.2\u2009mg\/kg\/day, 0.7\u2009mg\/kg\/day) experienced greater reduction from baseline in frequency of seizures associated with a fall versus placebo, which was sustained in the open\u2010label extension (OLE) study (NCT03355209). In this post hoc analysis, trajectories of fenfluramine effectiveness and safety, along with dose changes over time, are described for patients with LGS randomized to placebo in RCT who switched to fenfluramine in OLE (PBO\u2010FFA) and those who received fenfluramine in both RCT\/OLE (FFA\u2010FFA). Among patients who completed 12\u2009months in OLE (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009151), numerical improvements in effectiveness outcomes were seen in the PBO\u2010FFA group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200959) after initiating fenfluramine and were similar to those in the FFA\u2010FFA group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200992). Regression to the mean was not observed in the PBO\u2010FFA group, suggesting that changes were due to fenfluramine. Incidence of the most commonly reported treatment\u2010emergent adverse events increased in the PBO\u2010FFA group after fenfluramine initiation but decreased in the FFA\u2010FFA group in OLE. These data demonstrate rapid improvement in seizure frequency and global functioning in both groups with continued clinical improvement as the mean fenfluramine dose was increased. These results confirm that sustained fenfluramine treatment is effective and tolerable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>This study assessed the change over time in the number of seizures, overall improvement, and side effects in patients with LGS receiving placebo (no active medicine) or fenfluramine in a 14\u2010week study; all patients later received fenfluramine in the extension study. Overall, the number of seizures (associated with a fall) decreased once patients initially receiving placebo changed to fenfluramine (optimal effect around Month 4 while receiving a higher dose), but as expected, common side effects were reported more frequently once patients began fenfluramine treatment. Patients, parents, and doctors should be aware of this time course to allow fenfluramine enough time to work.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70320","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:14:41Z","timestamp":1785770081000},"page":"1871-1879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in effectiveness and safety in patients with Lennox\u2013Gastaut syndrome transitioning from the fenfluramine randomized controlled trial to open\u2010label extension study"],"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":"Necker Enfants Malades Hospital, APHP, Member of the European Reference Network (ERN) EpiCARE Reference Centre for Rare Epilepsies  Paris France"},{"name":"Institut Imagine, U 1163  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"}],"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\/0000-0002-7118-0139","authenticated-orcid":false,"given":"Lieven","family":"Lagae","sequence":"additional","affiliation":[{"name":"University of Leuven  Leuven Belgium"},{"name":"Leuven Childhood Epilepsy Center Leuven Brain Institute, UZ Leuven, Member of the ERN EpiCARE  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Austin Health University of Melbourne  Melbourne Victoria Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health University of Melbourne  Parkville Victoria Australia"},{"name":"University of Melbourne, Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-7079","authenticated-orcid":false,"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Meyer Children's Hospital IRCCS, Member of the ERN EpiCARE  Florence Italy"},{"name":"University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2081-8988","authenticated-orcid":false,"given":"Joseph","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences and Benioff Children's Hospital, University of California San Francisco  San Francisco California 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-4697","authenticated-orcid":false,"given":"Sameer M.","family":"Zuberi","sequence":"additional","affiliation":[{"name":"Paediatric Neurosciences Research Group, School of Health and Wellbeing University of Glasgow  Glasgow UK"},{"name":"Royal Hospital for Children  Glasgow UK"},{"name":"Queen Elizabeth University Hospital, Member of the ERN EpiCARE  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1122-3555","authenticated-orcid":false,"given":"Kate","family":"Riney","sequence":"additional","affiliation":[{"name":"The University of Queensland  St Lucia Queensland Australia"},{"name":"Queensland Children's Hospital  South Brisbane Queensland Australia"},{"name":"Children's Health Queensland Queensland Hospital and Health Service  South Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Healy","sequence":"additional","affiliation":[{"name":"UCB  Smyrna Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne","family":"Abraham","sequence":"additional","affiliation":[{"name":"UCB  Smyrna Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca Zhang","family":"Roper","sequence":"additional","affiliation":[{"name":"UCB  Slough UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Langlois","sequence":"additional","affiliation":[{"name":"UCB  Courbevoie 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