Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/53463 |
Resumo: | © 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessmentsDravet syndromeEchocardiographyFenfluramineLong-termSafety© 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Objective: To assess the cardiovascular safety of fenfluramine when used to treat children and young adults with Dravet syndrome. Methods: Patients with Dravet syndrome who completed one of three phase 3 clinical trials of fenfluramine could enroll in the open-label extension (OLE) study (NCT02823145). All patients started fenfluramine treatment at an oral dose of 0.2 mg/kg/day. The dose was titrated based on efficacy and tolerability to a maximum of 0.7 mg/kg/day (absolute maximum 26 mg/day) or 0.4 mg/kg/day (absolute maximum 17 mg/day) in patients concomitantly receiving stiripentol. Serial transthoracic echocardiography was performed using standardized methods and blinded readings at OLE entry, after 4-6 weeks, and every 3 months thereafter. Valvular heart disease (VHD) was defined as ≥ moderate mitral regurgitation or ≥ mild aortic regurgitation combined with physical signs or symptoms attributable to valve dysfunction. Pulmonary artery hypertension (PAH) was defined as systolic pulmonary artery pressure >35 mmHg. Results: A total of 327 patients (median age, 9.0 years; range, 2-19 years) have enrolled in the OLE and received ≥1 dose of fenfluramine. The median duration of treatment was 23.9 months (range, 0.2-42.6 months) and the median dose of fenfluramine was 0.44 mg/kg/day. No patient demonstrated VHD or PAH at any time during the OLE. Significance/interpretation: This study, which represents the largest, longest, and most rigorous examination of cardiovascular safety of fenfluramine yet reported, found no cases of VHD or PAH. These results, combined with fenfluramine's substantial antiseizure efficacy, support a strong positive benefit-risk profile for fenfluramine in the treatment of Dravet syndrome.ElsevierRepositório da Universidade de LisboaAgarwal, AnupamFarfel, Gail M.Gammaitoni, Arnold R.Wong, Pierre C.Pinto, Fausto J.Galer, Bradley S.2022-06-23T16:39:52Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53463engEur J Paediatr Neurol. 2022 May 24;39:35-391090-379810.1016/j.ejpn.2022.05.0061532-2130info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:59:14Zoai:repositorio.ul.pt:10451/53463Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:24.285098Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
title |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
spellingShingle |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments Agarwal, Anupam Dravet syndrome Echocardiography Fenfluramine Long-term Safety |
title_short |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
title_full |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
title_fullStr |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
title_full_unstemmed |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
title_sort |
Long-term cardiovascular safety of fenfluramine in patients with Dravet syndrome treated for up to 3 years: findings from serial echocardiographic assessments |
author |
Agarwal, Anupam |
author_facet |
Agarwal, Anupam Farfel, Gail M. Gammaitoni, Arnold R. Wong, Pierre C. Pinto, Fausto J. Galer, Bradley S. |
author_role |
author |
author2 |
Farfel, Gail M. Gammaitoni, Arnold R. Wong, Pierre C. Pinto, Fausto J. Galer, Bradley S. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Agarwal, Anupam Farfel, Gail M. Gammaitoni, Arnold R. Wong, Pierre C. Pinto, Fausto J. Galer, Bradley S. |
dc.subject.por.fl_str_mv |
Dravet syndrome Echocardiography Fenfluramine Long-term Safety |
topic |
Dravet syndrome Echocardiography Fenfluramine Long-term Safety |
description |
© 2022 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-06-23T16:39:52Z 2022 2022-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/53463 |
url |
http://hdl.handle.net/10451/53463 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Eur J Paediatr Neurol. 2022 May 24;39:35-39 1090-3798 10.1016/j.ejpn.2022.05.006 1532-2130 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134595012100096 |