ArticleFrontiers in neurology2021
Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis.
Article in Frontiers in neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Infection Risk During Rituximab Therapy in Multiple Sclerosis: Effect of Dosing Interval and Age.Neurology. Clinical practice · 2026Observational
- Understanding the Unmet Needs of People with MS at Diagnosis and Throughout Their Care Journey: Insights from a Survey-Based Study.Neurology and therapy · 2026Article
- The impact of age on efficacy and safety of disease modifying treatment-insights from the Austrian Multiple Sclerosis Treatment Registry.Journal of neurology · 2026Observational
- Comparative Effectiveness and Risk of Severe Infection in Adult Patients With MS Treated With Diroximel Fumarate Versus Anti-CD20 Monoclonal Antibodies: A Real-World Claims Analysis.Advances in therapy · 2026Article
- Cellular senescence in multiple sclerosis: hallmarks, immunosenescence, and therapeutic implications.Frontiers in immunology · 2026Review
- Modulation of the immunological and neuroinflammatory microenvironment in older people with multiple sclerosis.Frontiers in immunology · 2026Review
- Machine Learning Analysis Applied to Prediction of Early Progression Independent of Relapse Activity in Multiple Sclerosis Patients.European journal of neurology · 2025Article
- Matching-adjusted indirect comparisons of diroximel fumarate, ocrelizumab and interferon beta-1a for relapsing multiple sclerosis.Journal of comparative effectiveness research · 2025Article
- Impact of Age on Switching or Stopping Disease Modifying Therapies in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- De-Escalation Treatment Strategies From Natalizumab in Patients With Relapsing Multiple Sclerosis in Austria.European journal of neurology · 2025Article
- De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.Brain : a journal of neurology · 2025Review
- Treatment De-escalation in Relapsing-Remitting Multiple Sclerosis: An Observational Study.CNS drugs · 2025Observational
- Inflammatory disease in people with multiple sclerosis treated with immune checkpoint inhibitors.Annals of clinical and translational neurology · 2025Article
- De-Escalation of Disease-Modifying Therapy in Multiple Sclerosis-A Danish Nationwide Cohort Study.European journal of neurology · 2025Article
- Real-world infection risk in multiple sclerosis patients on long-term immunomodulatory treatments.Multiple sclerosis and related disorders · 2025Observational
- Aggressive treatment of early acute focal inflammatory activity to extend the window for BTK inhibition in multiple sclerosis.Therapeutic advances in neurological disorders · 2025Review
- A narrative review on the safety of glatiramer acetate in multiple sclerosis: focus on Europe.Therapeutic advances in chronic disease · 2025Review
- MS treatment de-escalation: review and commentary.Journal of neurology · 2024Review
- Predicting multiple sclerosis disease progression and outcomes with machine learning and MRI-based biomarkers: a review.Journal of neurology · 2024Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStrategies for sequencing disease modifying therapies (DMTs) in multiple sclerosis (MS) patients include escalation, high efficacy early, induction, and de-escalation.
objectiveTo provide a perspective on de-escalation, which aims to match the ratio of DMT benefit/risk in aging patients.
methodsWe 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.
resultsYounger 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.
conclusionIn 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.