Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/31005
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dc.contributor.authorKnupp, Kelly G-
dc.contributor.authorScheffer, Ingrid E-
dc.contributor.authorCeulemans, Berten-
dc.contributor.authorSullivan, Joseph-
dc.contributor.authorNickels, Katherine C-
dc.contributor.authorLagae, Lieven-
dc.contributor.authorGuerrini, Renzo-
dc.contributor.authorZuberi, Sameer M-
dc.contributor.authorNabbout, Rima-
dc.contributor.authorRiney, Kate-
dc.contributor.authorAgarwal, Anupam-
dc.contributor.authorLock, Michael-
dc.contributor.authorDai, David-
dc.contributor.authorFarfel, Gail M-
dc.contributor.authorGaler, Bradley S-
dc.contributor.authorGammaitoni, Arnold R-
dc.contributor.authorPolega, Shikha-
dc.contributor.authorDavis, Ronald-
dc.contributor.authorGil-Nagel, Antonio-
dc.date2022-
dc.date.accessioned2022-10-21T04:39:32Z-
dc.date.available2022-10-21T04:39:32Z-
dc.date.issued2023-
dc.identifier.citationEpilepsia 2023; 64(1)en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/31005-
dc.description.abstractTo evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on 0.2 mg/kg/day fenfluramine and, after 1 month, were titrated to effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months. As of 10/19/2020, 247 patients were enrolled in the OLE. Mean age was 14.3±7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2-4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was -28.6% over the entire OLE (n=241) and -50.5% at Month 15 (n=142) (P<0.0001); 75/241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in non-drop seizure frequency was -45.9% (n=192; P=0.0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (P<0.0001; n=106) and 35.8% (P<0.0001; n=186), respectively. A total of 37.6% (95% CI: 31.4%, 44.1%; n=237) of investigators and 35.2% of caregivers (95% CI: 29.1%, 41.8%; n=230) rated patients as "Much Improved"/"Very Much Improved" on the Clinical Global Impression of Improvement (CGI-I) scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for SUDEP. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.en
dc.language.isoeng-
dc.subjectLennox-Gastaut syndromeen
dc.subjectdevelopmental and epileptic encephalopathiesen
dc.subjectfenfluramineen
dc.subjectlong-term open-label extensionen
dc.titleFenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: interim analysis of an open-label extension study.en
dc.typeJournal Articleen
dc.identifier.journaltitleEpilepsiaen
dc.identifier.affiliationUniversity of Colorado, Children's Hospital Colorado, Aurora, CO, USA.en
dc.identifier.affiliationSchool of Clinical Medicine, University of Queensland, St Lucia, QLD, Australiaen
dc.identifier.affiliationNeuroscience Unit, Queensland Children's Hospital, South Brisbane, QLD, Australiaen
dc.identifier.affiliationAustin Healthen
dc.identifier.affiliationDepartment of Paediatric Neurology, Antwerp University Hospital, Antwerp, Belgium.en
dc.identifier.affiliationUniversity of California San Francisco Weill Institute for Neurosciences, Benioff Children's Hospital, San Francisco, CA, USA..en
dc.identifier.affiliationMayo Clinic, Department of Neurology, Rochester, MN, USA.en
dc.identifier.affiliationMember of the European Reference Network EpiCARE; Department of Paediatric Neurology, University of Leuven, Leuven, Belgium..en
dc.identifier.affiliationPediatric Neurology and Neurogenetics Unit, Anna Meyer Children's Hospital, University of Florence, Florence, Italy; IRCCS Fondazione Stella Maris, Pisa, Italy..en
dc.identifier.affiliationPaediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, United Kingdom..en
dc.identifier.affiliationReference Centre for Rare Epilepsies, Hôpital Universitaire Necker-Enfants Malades, APHP, Member of EPICARE, Institut Imagine, Université Paris Cité, Paris, France..en
dc.identifier.affiliationFormerly Zogenix, Inc. (now a part of UCB), Emeryville, CA, USA..en
dc.identifier.affiliationIndependent consultant, Zogenix, Inc. (now a part of UCB); Haiku, HI, USA..en
dc.identifier.affiliationSyneos Health, Morrisville, NC, USA..en
dc.identifier.affiliationFormerly Zogenix, Inc. (now a part of UCB), Emeryville, CA, USA..en
dc.identifier.affiliationZogenix, Inc. (now a part of UCB), Emeryville, CA, USA..en
dc.identifier.affiliationNeurology and Epilepsy Research Center, Orlando, FL, USA..en
dc.identifier.affiliationHospital Ruber Internacional, Madrid, Spain..en
dc.identifier.doi10.1111/epi.17431en
dc.type.contentTexten
dc.identifier.orcidhttps://orcid.org/0000-0002-1967-0827en
dc.identifier.orcidhttps://orcid.org/0000-0002-2311-2174en
dc.identifier.orcidhttps://orcid.org/0000-0002-6579-3035en
dc.identifier.orcidhttps://orcid.org/0000-0002-7118-0139en
dc.identifier.orcidhttps://orcid.org/0000-0002-7272-7079en
dc.identifier.orcidhttps://orcid.org/0000-0001-5877-4074en
dc.identifier.orcidhttps://orcid.org/0000-0002-1122-3555en
dc.identifier.orcidhttps://orcid.org/0000-0002-4735-3327en
dc.identifier.orcidhttps://orcid.org/0000-0002-4775-2862en
dc.identifier.pubmedid36196777-
local.name.researcherScheffer, Ingrid E
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
crisitem.author.deptEpilepsy Research Centre-
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