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Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study
The aim of this study was to evaluate short-term safety and tolerability of fingolimod in a real-world population with relapsing multiple sclerosis, focusing on cardiac safety during treatment initiation. Patients received fingolimod 0.5 mg once daily for four months. Patients excluded from the pivo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915082/ https://www.ncbi.nlm.nih.gov/pubmed/24221641 http://dx.doi.org/10.1007/s00415-013-7115-8 |
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author | Gold, Ralf Comi, Giancarlo Palace, Jacqueline Siever, Arno Gottschalk, Rebecca Bijarnia, Mahendra von Rosenstiel, Philipp Tomic, Davorka Kappos, Ludwig |
author_facet | Gold, Ralf Comi, Giancarlo Palace, Jacqueline Siever, Arno Gottschalk, Rebecca Bijarnia, Mahendra von Rosenstiel, Philipp Tomic, Davorka Kappos, Ludwig |
author_sort | Gold, Ralf |
collection | PubMed |
description | The aim of this study was to evaluate short-term safety and tolerability of fingolimod in a real-world population with relapsing multiple sclerosis, focusing on cardiac safety during treatment initiation. Patients received fingolimod 0.5 mg once daily for four months. Patients excluded from the pivotal studies with certain pre-existing cardiac conditions or baseline cardiac findings (PCCs), and those receiving beta blockers (BBs) and/or calcium channel blockers (CCBs), were eligible. Heart rate (HR) and electrical conduction events were monitored using ambulatory electrocardiography for at least 6 h after the first dose. Of 2,417 enrolled patients, 2,282 (94.4 %) completed the study. Fingolimod initiation was associated with a transient, mostly asymptomatic decrease in HR. Bradycardia adverse events occurred in 0.6 % of patients and were more frequent in individuals receiving BBs/CCBs (3.3 %) than in other patient subgroups (0.5–1.4 %); most events were asymptomatic, and all patients recovered without pharmacological intervention. In the 6 h post-dose, the incidences of Mobitz type I second-degree atrioventricular block (AVB) and 2:1 AVB were higher in patients with PCCs (4.1 and 2.0 %, respectively) than in those without (0.9 and 0.3 %, respectively); at pre-dose screening, patients with PCCs had the same incidence of Mobitz type I second-degree AVB (4.1 %) and a slightly lower incidence of 2:1 AVB (0.7 %) than 6 h post-dose. All recorded conduction abnormalities were asymptomatic. This study adds to the evidence showing that cardiac effects during fingolimod initiation remain consistent with those known from previous, controlled studies, even if patients with PCCs are included. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00415-013-7115-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3915082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-39150822014-02-10 Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study Gold, Ralf Comi, Giancarlo Palace, Jacqueline Siever, Arno Gottschalk, Rebecca Bijarnia, Mahendra von Rosenstiel, Philipp Tomic, Davorka Kappos, Ludwig J Neurol Original Communication The aim of this study was to evaluate short-term safety and tolerability of fingolimod in a real-world population with relapsing multiple sclerosis, focusing on cardiac safety during treatment initiation. Patients received fingolimod 0.5 mg once daily for four months. Patients excluded from the pivotal studies with certain pre-existing cardiac conditions or baseline cardiac findings (PCCs), and those receiving beta blockers (BBs) and/or calcium channel blockers (CCBs), were eligible. Heart rate (HR) and electrical conduction events were monitored using ambulatory electrocardiography for at least 6 h after the first dose. Of 2,417 enrolled patients, 2,282 (94.4 %) completed the study. Fingolimod initiation was associated with a transient, mostly asymptomatic decrease in HR. Bradycardia adverse events occurred in 0.6 % of patients and were more frequent in individuals receiving BBs/CCBs (3.3 %) than in other patient subgroups (0.5–1.4 %); most events were asymptomatic, and all patients recovered without pharmacological intervention. In the 6 h post-dose, the incidences of Mobitz type I second-degree atrioventricular block (AVB) and 2:1 AVB were higher in patients with PCCs (4.1 and 2.0 %, respectively) than in those without (0.9 and 0.3 %, respectively); at pre-dose screening, patients with PCCs had the same incidence of Mobitz type I second-degree AVB (4.1 %) and a slightly lower incidence of 2:1 AVB (0.7 %) than 6 h post-dose. All recorded conduction abnormalities were asymptomatic. This study adds to the evidence showing that cardiac effects during fingolimod initiation remain consistent with those known from previous, controlled studies, even if patients with PCCs are included. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00415-013-7115-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2013-11-13 2014 /pmc/articles/PMC3915082/ /pubmed/24221641 http://dx.doi.org/10.1007/s00415-013-7115-8 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Communication Gold, Ralf Comi, Giancarlo Palace, Jacqueline Siever, Arno Gottschalk, Rebecca Bijarnia, Mahendra von Rosenstiel, Philipp Tomic, Davorka Kappos, Ludwig Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
title | Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
title_full | Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
title_fullStr | Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
title_full_unstemmed | Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
title_short | Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
title_sort | assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a phase 3b, open-label study |
topic | Original Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915082/ https://www.ncbi.nlm.nih.gov/pubmed/24221641 http://dx.doi.org/10.1007/s00415-013-7115-8 |
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