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Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies

INTRODUCTION: Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. METH...

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Autores principales: Amezcua, Lilyana, Mao-Draayer, Yang, Vargas, Wendy S., Farber, Rebecca, Schaefer, Sara, Branco, Filipe, England, Sarah M., Belviso, Nicholas, Lewin, James B., Mendoza, Jason P., Shankar, Sai L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195942/
https://www.ncbi.nlm.nih.gov/pubmed/37061656
http://dx.doi.org/10.1007/s40120-023-00475-8
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author Amezcua, Lilyana
Mao-Draayer, Yang
Vargas, Wendy S.
Farber, Rebecca
Schaefer, Sara
Branco, Filipe
England, Sarah M.
Belviso, Nicholas
Lewin, James B.
Mendoza, Jason P.
Shankar, Sai L.
author_facet Amezcua, Lilyana
Mao-Draayer, Yang
Vargas, Wendy S.
Farber, Rebecca
Schaefer, Sara
Branco, Filipe
England, Sarah M.
Belviso, Nicholas
Lewin, James B.
Mendoza, Jason P.
Shankar, Sai L.
author_sort Amezcua, Lilyana
collection PubMed
description INTRODUCTION: Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; years 0–2 DEFINE/CONFIRM), then DMF (years 3–10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18–29 years. RESULTS: Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0–10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16–0.35) vs. 0.56 (0.35–0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01–0.47) at years 9–10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]). CONCLUSION: The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. CLINICAL TRIAL INFORMATION: Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00475-8.
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spelling pubmed-101959422023-05-20 Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies Amezcua, Lilyana Mao-Draayer, Yang Vargas, Wendy S. Farber, Rebecca Schaefer, Sara Branco, Filipe England, Sarah M. Belviso, Nicholas Lewin, James B. Mendoza, Jason P. Shankar, Sai L. Neurol Ther Original Research INTRODUCTION: Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. METHODS: Randomized patients received DMF 240 mg twice daily or placebo (PBO; years 0–2 DEFINE/CONFIRM), then DMF (years 3–10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18–29 years. RESULTS: Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0–10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16–0.35) vs. 0.56 (0.35–0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01–0.47) at years 9–10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]). CONCLUSION: The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. CLINICAL TRIAL INFORMATION: Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00475-8. Springer Healthcare 2023-04-15 /pmc/articles/PMC10195942/ /pubmed/37061656 http://dx.doi.org/10.1007/s40120-023-00475-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research
Amezcua, Lilyana
Mao-Draayer, Yang
Vargas, Wendy S.
Farber, Rebecca
Schaefer, Sara
Branco, Filipe
England, Sarah M.
Belviso, Nicholas
Lewin, James B.
Mendoza, Jason P.
Shankar, Sai L.
Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies
title Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies
title_full Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies
title_fullStr Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies
title_full_unstemmed Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies
title_short Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies
title_sort efficacy of dimethyl fumarate in young adults with relapsing-remitting multiple sclerosis: analysis of the define, confirm, and endorse studies
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195942/
https://www.ncbi.nlm.nih.gov/pubmed/37061656
http://dx.doi.org/10.1007/s40120-023-00475-8
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