{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:52:04Z","timestamp":1791996724507,"version":"4.4.0"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"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"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The most common primary endpoint for assessing treatment efficacy in patients with Lennox\u2013Gastaut syndrome (LGS) is change in frequency of seizures associated with a fall. Increased number of seizure\u2010free days (SFDs) is more strongly associated with improved quality of life than seizure frequency reduction. Fenfluramine is approved for treatment of seizures associated with LGS in patients \u22652\u2009years old. Data from a fenfluramine randomized controlled trial (RCT) in patients with LGS, and its open\u2010label extension (OLE), were used to evaluate (1) mean change in percentage of SFDs (seizures associated with a fall, generalized tonic\u2013clonic seizures, all countable [motor] seizures) from baseline overall and by baseline seizure quartile; and (2) relationships between percentage of SFDs and change in seizure frequency, and Clinical Global Impression\u2013Improvement (CGI\u2013I) scale scores. Fenfluramine treatment was associated with a greater increase in percentage of SFDs versus placebo (RCT; all seizure categories,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.0001), and higher doses corresponded to greater percentages (OLE) consistently across baseline seizure quartiles. SFD correlations with seizure frequency were strong (\n                    <jats:italic>\u03c1<\/jats:italic>\n                    \u2009=\u2009\u2212.776 to \u2212.974); SFD correlations with CGI\u2013I score were weak\/modest (\n                    <jats:italic>\u03c1<\/jats:italic>\n                    \u2009=\u2009\u2212.2494 to \u2212.3203). Assessment of SFDs enhances the evaluation of treatment efficacy and may be clinically meaningful for patients with LGS and their families.\n                  <\/jats:p>","DOI":"10.1002\/epi.70536","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:25:13Z","timestamp":1791995113000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fenfluramine treatment and seizure\u2010free days in pediatric and adult patients with Lennox\u2013Gastaut syndrome: A post hoc analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-9749","authenticated-orcid":false,"given":"St\u00e9phane","family":"Auvin","sequence":"first","affiliation":[{"name":"L'Assistance Publique \u2010 H\u00f4pitaux de Paris Reference Center for Rare Epilepsies, member of European Reference Network EpiCARE, H\u00f4pital Universitaire Robert Debr\u00e9  Paris France"},{"name":"Institut Hospitalo\u2010Universitaire Robert\u2010Debr\u00e9 du Cerveau de I'Enfant  Paris France"},{"name":"Universit\u00e9 Paris\u2010Cit\u00e9, Inserm NeuroDiderot  Paris France"},{"name":"Institut Universitaire de France  Paris France"}],"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":"University of Melbourne, Austin Health  Heidelberg Victoria Australia"},{"name":"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\/0000-0003-4515-0793","authenticated-orcid":false,"given":"Antonio","family":"Gil\u2010Nagel","sequence":"additional","affiliation":[{"name":"Hospital Ruber Internacional  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Healy","sequence":"additional","affiliation":[{"name":"UCB  Smyrna Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9337-054X","authenticated-orcid":false,"given":"Am\u00e9lie","family":"Lothe","sequence":"additional","affiliation":[{"name":"UCB  Courbevoie France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Langlois","sequence":"additional","affiliation":[{"name":"UCB  Courbevoie France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne","family":"Abraham","sequence":"additional","affiliation":[{"name":"UCB  Smyrna Georgia 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 European Reference Network EpiCARE  Leuven Belgium"}],"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"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/epi.17241","article-title":"International League Against Epilepsy 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and future strategies","volume":"35","author":"Strzelczyk A","year":"2021","journal-title":"CNS Drugs"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1111\/epi.17618","article-title":"Seizure\u2010free days as a novel outcome in patients with Lennox\u2010Gastaut syndrome: post hoc analysis of patients receiving cannabidiol in two randomized controlled trials","volume":"64","author":"Auvin S","year":"2023","journal-title":"Epilepsia"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1002\/epi4.70118","article-title":"Nonseizure symptoms and broader seizure impacts in patients with Dravet syndrome and Lennox\u2010Gastaut syndrome in clinical practice settings: results from a multinational survey","volume":"10","author":"Shah D","year":"2025","journal-title":"Epilepsia Open"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1212\/WNL.0000000000003685","article-title":"Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: report of the guideline development, dissemination, and implementation Subcommittee of the American Academy of neurology and the American Epilepsy Society","volume":"88","author":"Harden C","year":"2017","journal-title":"Neurology"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s40120-023-00510-8","article-title":"Determining the relationship between seizure\u2010free days and other predictors of quality of life in patients with Dravet syndrome and their carers from FFA registration studies","volume":"12","author":"Pinsent A","year":"2023","journal-title":"Neurol Ther"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/epi4.12314","article-title":"Novel seizure outcomes in patients with Lennox\u2010Gastaut syndrome: post hoc analysis of seizure\u2010free days in rufinamide study 303","volume":"4","author":"Auvin S","year":"2019","journal-title":"Epilepsia Open"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.yebeh.2021.108239","article-title":"The impact of seizure frequency on quality of life in patients with Lennox\u2010Gastaut syndrome or Dravet syndrome","volume":"123","author":"Auvin S","year":"2021","journal-title":"Epilepsy Behav"},{"key":"e_1_2_10_12_1","volume-title":"FINTEPLA\u00ae (fenfluramine) oral solution [prescribing information]","year":"2025"},{"key":"e_1_2_10_13_1","volume-title":"Fintepla 2.2 mg\/mL oral solution [summary of product characteristics]","year":"2024"},{"key":"e_1_2_10_14_1","volume-title":"Fintepla 2.2 mg\/ml oral solution [summary of product characteristics]","year":"2024"},{"key":"e_1_2_10_15_1","unstructured":"Nippon Shinyaku Co. Ltd.UCB Japan obtained additional application of fintepla\u00ae(fenfluramine) for the treatment of seizures associated with Lennox\u2010Gastaut syndrome in Japan.2024. Available from:https:\/\/www.nippon\u2010shinyaku.co.jp\/file\/download.php?file_id=7484. Accessed 28 Mar 2024."},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1001\/jamaneurol.2022.0829","article-title":"Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox\u2010Gastaut syndrome: a randomized clinical trial","volume":"79","author":"Knupp K","year":"2022","journal-title":"JAMA Neurol"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.yebeh.2025.110753","article-title":"Final analysis from an open\u2010label extension study of fenfluramine for the treatment of seizures in Lennox\u2010Gastaut syndrome: long\u2010term impact on patients and caregivers","volume":"173","author":"Knupp KG","year":"2025","journal-title":"Epilepsy Behav"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1177\/17407745231160074","article-title":"Using modified intention\u2010to\u2010treat as a principal stratum estimator for failure to initiate treatment","volume":"20","author":"Kahan BC","year":"2023","journal-title":"Clin Trials"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/epi.17106","article-title":"Fenfluramine significantly reduces day\u2010to\u2010day seizure burden by increasing number of seizure\u2010free days and time between seizures in patients with Dravet syndrome: a time\u2010to\u2010event analysis","volume":"63","author":"Sullivan J","year":"2022","journal-title":"Epilepsia"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1714631","article-title":"Effect of cannabidiol on drop seizures in the Lennox\u2010Gastaut syndrome","volume":"378","author":"Devinsky O","year":"2018","journal-title":"N Engl J Med"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebr.2021.100508","article-title":"Quantifying the burden of disease in patients with Lennox Gastaut syndrome","volume":"16","author":"Spoor JKH","year":"2021","journal-title":"Epilepsy Behav Rep"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70536","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70536","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70536","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:25:18Z","timestamp":1791995118000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":20,"alternative-id":["10.1002\/epi.70536"],"URL":"https:\/\/doi.org\/10.1002\/epi.70536","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"epi.70536"}}