{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:19:14Z","timestamp":1789100354410,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,4]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n Stiripentol, fenfluramine, and cannabidiol are licensed add\u2010on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first\u2010line add\u2010on therapies in DS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a systematic review and frequentist network meta\u2010analysis (NMA) of randomized controlled trial (RCT) data for licensed add\u2010on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of \u226550% (clinically meaningful), \u226575% (profound), and 100% (seizure\u2010free); serious adverse events (SAEs); discontinuations due to AEs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified relevant data from two placebo\u2010controlled RCTs for each drug. Stiripentol 50\u2009mg\/kg\/day and fenfluramine 0.7\u2009mg\/kg\/day had similar efficacy in achieving \u226550% (clinically meaningful) and \u226575% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: \u221220% to 22%;\n p<\/jats:italic>\n \u2009=\u20090.93] and 6% [\u221215% to 27%;\n p<\/jats:italic>\n \u2009=\u20090.59], respectively), and both were statistically superior (\n p<\/jats:italic>\n \u2009<\u20090.05) to licensed dose regimens of cannabidiol (10 or 20\u2009mg\/kg\/day, with\/irrespective of clobazam) for these outcomes. Stiripentol was statistically superior in achieving seizure\u2010free intervals compared to fenfluramine (RD\u2009=\u200926% [CI: 8% to 44%;\n p<\/jats:italic>\n \u2009<\u20090.01]) and licensed dose regimens of cannabidiol. There were no significant differences in the proportions of patients experiencing SAEs. The risk of discontinuations due to AEs was lower for stiripentol, although the stiripentol trials were shorter.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n This NMA of RCT data indicates stiripentol, as a first\u2010line add\u2010on therapy in DS, is at least as effective as fenfluramine and both are more effective than cannabidiol in reducing convulsive seizures. No significant difference in the incidence of SAEs between the three add\u2010on agents was observed, but stiripentol may have a lower risk of discontinuations due to AEs. These results may inform clinical decision\u2010making and the continued development of guidelines for the treatment of people with DS.<\/jats:p>\n <\/jats:sec>\n \n Plain Language Summary<\/jats:title>\n This study compared three drugs (stiripentol, fenfluramine, and cannabidiol) used alongside other medications for managing seizures in a severe type of epilepsy called DS. The study found that stiripentol and fenfluramine were similarly effective in reducing seizures and both were more effective than cannabidiol. Stiripentol was the best drug for stopping seizures completely based on the available clinical trial data. All three drugs had similar rates of serious side effects, but stiripentol had a lower chance of being stopped due to side effects. This information can help guide treatment choices for people with DS.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi4.12923","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T10:53:59Z","timestamp":1709290439000},"page":"689-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Comparative efficacy and safety of stiripentol, cannabidiol and fenfluramine as first\u2010line add\u2010on therapies for seizures in Dravet syndrome: A network meta\u2010analysis"],"prefix":"10.1002","volume":"9","author":[{"given":"Renzo","family":"Guerrini","sequence":"first","affiliation":[{"name":"Neuroscience Department Children's Hospital Meyer IRCCS Florence Italy"},{"name":"University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-1694","authenticated-orcid":false,"given":"Catherine","family":"Chiron","sequence":"additional","affiliation":[{"name":"INSERM U1141, NeuroDiderot Universit\u00e9 Paris Cit\u00e9 Paris France"},{"name":"Pediatric Neurology and Reference Center for Rare Epilepsies APHP, Necker\u2010Enfants Malades Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3388-9231","authenticated-orcid":false,"given":"Delphine","family":"Vandame","sequence":"additional","affiliation":[{"name":"Orphan Disease Division (HQ) Biocodex Gentilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2587-3564","authenticated-orcid":false,"given":"Warren","family":"Linley","sequence":"additional","affiliation":[{"name":"Paragon Market Access Ltd Chorley Lancashire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4522-4994","authenticated-orcid":false,"given":"Toby","family":"Toward","sequence":"additional","affiliation":[{"name":"Henley Health Economics Ltd Henley\u2010on\u2010Thames Oxfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2011.02994.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2016.243"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2017.08.029"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.06.008"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2016.10.006"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.09.007"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13591"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)05114-9"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17274"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-022-00898-1"},{"key":"e_1_2_12_12_1","unstructured":"National Institute for Health and Care Excellence.NICE Guideline NG217: Epilepsies in children young people and adults.2022. 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