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Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results

BACKGROUND: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. OBJECTIVE: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. METHODS:...

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Autores principales: Gold, Ralf, Arnold, Douglas L, Bar-Or, Amit, Fox, Robert J, Kappos, Ludwig, Mokliatchouk, Oksana, Jiang, Xiaotong, Lyons, Jennifer, Kapadia, Shivani, Miller, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978463/
https://www.ncbi.nlm.nih.gov/pubmed/34465252
http://dx.doi.org/10.1177/13524585211037909
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author Gold, Ralf
Arnold, Douglas L
Bar-Or, Amit
Fox, Robert J
Kappos, Ludwig
Mokliatchouk, Oksana
Jiang, Xiaotong
Lyons, Jennifer
Kapadia, Shivani
Miller, Catherine
author_facet Gold, Ralf
Arnold, Douglas L
Bar-Or, Amit
Fox, Robert J
Kappos, Ludwig
Mokliatchouk, Oksana
Jiang, Xiaotong
Lyons, Jennifer
Kapadia, Shivani
Miller, Catherine
author_sort Gold, Ralf
collection PubMed
description BACKGROUND: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. OBJECTIVE: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0–2), then DMF (Years 3–10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. RESULTS: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04–10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF (n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120–0.169)), while for PBO/DMF (n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0–2 years, 0.330 (95% CI, 0.266–0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118–0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. CONCLUSION: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF’s positive benefit/risk profile for long-term RRMS treatment.
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spelling pubmed-89784632022-04-05 Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results Gold, Ralf Arnold, Douglas L Bar-Or, Amit Fox, Robert J Kappos, Ludwig Mokliatchouk, Oksana Jiang, Xiaotong Lyons, Jennifer Kapadia, Shivani Miller, Catherine Mult Scler Original Research Papers BACKGROUND: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. OBJECTIVE: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0–2), then DMF (Years 3–10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. RESULTS: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04–10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF (n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120–0.169)), while for PBO/DMF (n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0–2 years, 0.330 (95% CI, 0.266–0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118–0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. CONCLUSION: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF’s positive benefit/risk profile for long-term RRMS treatment. SAGE Publications 2021-09-01 2022-04 /pmc/articles/PMC8978463/ /pubmed/34465252 http://dx.doi.org/10.1177/13524585211037909 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Papers
Gold, Ralf
Arnold, Douglas L
Bar-Or, Amit
Fox, Robert J
Kappos, Ludwig
Mokliatchouk, Oksana
Jiang, Xiaotong
Lyons, Jennifer
Kapadia, Shivani
Miller, Catherine
Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results
title Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results
title_full Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results
title_fullStr Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results
title_full_unstemmed Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results
title_short Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results
title_sort long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: final endorse study results
topic Original Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978463/
https://www.ncbi.nlm.nih.gov/pubmed/34465252
http://dx.doi.org/10.1177/13524585211037909
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