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Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis

BACKGROUND: Strategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation. OBJECTIVE: To provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patient...

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Autores principales: Vollmer, Brandi L., Wolf, Andrew B., Sillau, Stefan, Corboy, John R., Alvarez, Enrique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821102/
https://www.ncbi.nlm.nih.gov/pubmed/35145470
http://dx.doi.org/10.3389/fneur.2021.799138
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author Vollmer, Brandi L.
Wolf, Andrew B.
Sillau, Stefan
Corboy, John R.
Alvarez, Enrique
author_facet Vollmer, Brandi L.
Wolf, Andrew B.
Sillau, Stefan
Corboy, John R.
Alvarez, Enrique
author_sort Vollmer, Brandi L.
collection PubMed
description BACKGROUND: Strategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation. OBJECTIVE: To provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patients. METHODS: We reanalyzed data from a retrospective, real-world cohort of MS patients to model disease activity for oral (dimethyl fumarate and fingolimod) and higher efficacy infusible (natalizumab and rituximab) DMTs by age. For patients with relapsing MS, we conducted a controlled, stratified analysis examining odds of disease activity for oral vs. infusible DMTs in patients <45 or ≥45 years. We reviewed the literature to identify DMT risks and predictors of safe discontinuation. RESULTS: Younger patients had lower probability of disease activity on infusible vs. oral DMTs. There was no statistical difference after age 54.2 years. When dichotomized, patients <45 years on oral DMTs had greater odds of disease activity compared to patients on infusible DMTs, while among those ≥45 years, there was no difference. Literature review noted that adverse events increase with aging, notably infections in patients with higher disability and longer DMT duration. Additionally, we identified factors predictive of disease reactivation including age, clinical stability, and MRI activity. CONCLUSION: In a real-world cohort of relapsing MS patients, high efficacy DMTs had less benefit with aging but were associated with increased risks. This cohort helps overcome some limitations of trials where older patients were excluded. To better balance benefits/risks, we propose a DMT de-escalation approach for aging MS patients.
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spelling pubmed-88211022022-02-09 Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis Vollmer, Brandi L. Wolf, Andrew B. Sillau, Stefan Corboy, John R. Alvarez, Enrique Front Neurol Neurology BACKGROUND: Strategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation. OBJECTIVE: To provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patients. METHODS: We reanalyzed data from a retrospective, real-world cohort of MS patients to model disease activity for oral (dimethyl fumarate and fingolimod) and higher efficacy infusible (natalizumab and rituximab) DMTs by age. For patients with relapsing MS, we conducted a controlled, stratified analysis examining odds of disease activity for oral vs. infusible DMTs in patients <45 or ≥45 years. We reviewed the literature to identify DMT risks and predictors of safe discontinuation. RESULTS: Younger patients had lower probability of disease activity on infusible vs. oral DMTs. There was no statistical difference after age 54.2 years. When dichotomized, patients <45 years on oral DMTs had greater odds of disease activity compared to patients on infusible DMTs, while among those ≥45 years, there was no difference. Literature review noted that adverse events increase with aging, notably infections in patients with higher disability and longer DMT duration. Additionally, we identified factors predictive of disease reactivation including age, clinical stability, and MRI activity. CONCLUSION: In a real-world cohort of relapsing MS patients, high efficacy DMTs had less benefit with aging but were associated with increased risks. This cohort helps overcome some limitations of trials where older patients were excluded. To better balance benefits/risks, we propose a DMT de-escalation approach for aging MS patients. Frontiers Media S.A. 2022-01-25 /pmc/articles/PMC8821102/ /pubmed/35145470 http://dx.doi.org/10.3389/fneur.2021.799138 Text en Copyright © 2022 Vollmer, Wolf, Sillau, Corboy and Alvarez. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Vollmer, Brandi L.
Wolf, Andrew B.
Sillau, Stefan
Corboy, John R.
Alvarez, Enrique
Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis
title Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis
title_full Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis
title_fullStr Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis
title_full_unstemmed Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis
title_short Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis
title_sort evolution of disease modifying therapy benefits and risks: an argument for de-escalation as a treatment paradigm for patients with multiple sclerosis
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821102/
https://www.ncbi.nlm.nih.gov/pubmed/35145470
http://dx.doi.org/10.3389/fneur.2021.799138
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