Worldwide, the average age of people with multiple sclerosis (MS) has increased significantly over the past several decades. Findings from natural history studies reveal that the risk of new relapse and MRI activity diminishes with age. Available since 1993, the use of disease-modifying therapies (DMTs) for MS has expanded dramatically, with many patients using the drugs indefinitely. The participants of most phase 3 clinical trials that have resulted in regulatory approval of MS DMTs have been 55 years or younger at the onset of participation, so there remains a dearth of data as to the benefits and risks of DMT use in older people with MS. Risks associated with DMT use may increase as people age, especially vascular and malignancy comorbidities. Although some people with MS older than 55 years have discontinued DMT, some are reluctant to even consider a trial off DMT. Findings from many observational DMT discontinuation studies and 2 discontinuation randomized controlled trials have confirmed that the greatest risk of recurrent MS disease activity is in younger patients who discontinue DMT. For clinically stable people older than 60 years, the greatest enhanced risk faced by those who discontinue DMT is that of 1 to 2 brain MRI-detected lesions of unclear long-term clinical significance. Thus, although it may be reasonable to consider a personal DMT discontinuation or de-escalation trial, patients, their families, and MS clinicians would benefit from a substantial increase in clinical studies relevant to the risks and benefits of DMT use and nonuse in those older than 55 years.

The authors would like to thank the Consortium of Multiple Sclerosis Centers for supporting the concept and the meeting that resulted in the publication of this and other related manuscripts on aging in MS.

John R. Corboy, MD, MA, has received compensation as the medical director of the Rocky Mountain MS Center and associate editor of the 

. He has received research support from EMD Serono, the National Institutes of Health via the Immune Tolerance Network, and the National Multiple Sclerosis Society. Jeff Wilken, PhD, has been a speaker for Biogen, EMD Serono, and Sanofi; has been a paid consultant for Bayer and Sanofi; and has received research funding from Biogen and Sanofi. Ruth Ann Marrie, MD, PhD, FRCPC, receives research funding from the Arthritis Society Canada, the Canadian Institutes of Health Research, Children’s Hospital Research Institute of Manitoba, Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Manitoba Medical Service Foundation, MS Canada, National Multiple Sclerosis Society, The Pfizer Foundation, Public Health Agency of Canada, and the US Department of Defense. She is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada and holds the Gillian’s Hope Multiple Sclerosis Clinical Research Chair (Dalhousie University). Jacquelyn Bainbridge, PharmD, has served on advisory boards for EMD Serono, Novartis, and TG Therapeutics. Renee Stewart, DNP, APRN, has been on an advisory board for Genentech. Rachael Stacom, NP, has served on advisory boards for Genentech and TG Therapeutics. Frederick W. Foley, PhD, has been on advisory boards for Bayer and Biogen, has been a paid consultant for Biogen, and has been a speaker for EMD Serono and Sanofi. Le H. Hua, MD, has received personal fees for speaking, consulting, and advisory board activities from Alexion, EMD Serono, Genentech, Genzyme, Horizon, Novartis, and TG Therapeutics and has had research support paid to her institution from Genentech outside the submitted work. Authors Patty Bobryk, MHS, PT, MSCS, ATP; Jennifer S. Graves, MD, PhD, MAS; Mona D. Bostick, RDN, LDN; Maureen T. Choman, MD; Scott D. Newsome, DO, MSCS; Sarah A. Morrow, MD, MS, FRCPC; and Yinan Zhang, MD, have declared no relevant disclosures.

John R. Corboy, MD, MA

Sarah A. Morrow, MD, MS, FRCPC

Patty Bobryk, MHS, PT, MSCS, AT

Jeff Wilken, PhD

Jennifer S. Graves, MD, PhD, MAS

Ruth Ann Marrie, MD, PhD, FRCPC

Jacquelyn Bainbridge, PharmD

Renee Stewart, DNP, APRN

Rachael Stacom, NP

Mona D. Bostick, RDN, LDN

Maureen T. Choman, MD

Frederick W. Foley, PhD

Yinan Zhang, MD

Scott D. Newsome, DO, MSCS

Le H. Hua, MD

Clinicians should be informed about and able to discuss the changing risks and benefits of disease-modifying therapies (DMTs) as they relate to older people with multiple sclerosis (MS).

Discontinuation or de-escalation approaches may be reasonable for older people with MS with no recent relapse or MRI activity, those who have continued to experience slow progression despite ongoing use of DMT, and those with enhanced risks due to a combination of comorbidities and the DMTs themselves (eg, sphingosine-1-phosphate modulators).

DMT discontinuation in people with MS older than 60 years with no recent relapse or MRI activity primarily results in a small increase in MRI-detected lesions of unclear long-term clinical significance.

Ongoing clinical and MRI monitoring is essential in older people with MS, especially if they discontinue or de-escalate DMT. Findings from future studies may reveal serum or other nonimaging markers of disease prognosis to help guide decision-making.

More data are needed to ascertain the actual risks and benefits of DMT use, discontinuation, and de-escalation in older people with MS.

Often diagnosed as young adults, people with multiple sclerosis (MS) may live for decades with variable manifestations of the disease, including either stability or slow worsening of neurological disability, as they age. Since 1993, regulatory agencies around the world have approved over 25 disease-modifying therapies (DMTs) that alter the natural history of the disease in profound ways, resulting in longer lives and less disability for those affected by MS. The expanding armamentarium of DMTs, with their variable benefits, adverse effects, and risks, has resulted in a dramatic change in discussions of risks and benefits of these powerful drugs, especially because as people with MS age, the pathological, clinical, and radiological manifestations of MS change,

 as has been discussed in other manuscripts in this series. The consequences of these changes and the limitations in our knowledge about the use of MS DMTs in older adults are highlighted in this article.

Several factors are relevant to the use of DMT in aging people with MS. Relapses and active gadolinium-enhancing and new T2-hyperintense MRI-detected lesions diminish with age.

 There is, however, no maximum known age at which there is no risk of new or ongoing relapses, inflammatory MRI-detected lesions, or disability progression. Although relatively common even in younger people, the clinical progression of disability independent of relapses and/or active new MRI-detected lesions is substantially greater in older patients.

Current DMTs are primarily directed against the adaptive immune system, which is most active in younger people with relapsing MS,

 and have shown minimal benefit in older people with MS who primarily experience progression independent of acute inflammatory activity manifested by relapses and/or new, active MRI-detected lesions.

 Although 46% of adults with MS living in the United States are 55 years or older,

 there are minimal data available about the risks and benefits of DMT use in this population, as those older than 55 years have been excluded from the vast majority of controlled clinical trials. Thus, although most subgroup analyses and meta-analyses of these studies have concluded that there is diminished benefit of current DMTs above the age of 40 years

 and no clear benefit in reducing progression of disability above the age of 53 years,

 all these reviews are limited by minimal data in those older than 55 years. Notably, and for many different reasons, many older people with MS have discontinued DMT use.

 Conversely, among middle-aged people with MS who remain on DMT, the vast majority are unwilling to consider a trial off their DMT.

 Thus, use of MS DMT remains highly variable in people with MS older than 55 years.

A related issue is the role and potential benefit of DMTs in those with late-onset MS (LOMS), typically defined as people with first symptoms at 50 years or older, which occurs in approximately 5% of MS incident cases.

 A recent retrospective propensity-matched study of 436 participants with relapsing-onset disease 55 years or older in the Observatoire Français de la Sclérose en Plaques (OFSEP) registry compared outcomes between those who were treated with DMT and those who were not (218 in each group). Mean age at onset was 59.3 years, and median follow-up was over 5 years. Mean time to first relapse (the primary outcome) and time to first MRI activity were longer in those treated with DMT; however, median time to confirmed disability progression, progression independent of relapse activity (PIRA), and secondary progressive MS (SPMS) diagnosis were not delayed by treatment. The risk of serious infection was no different between groups.

Compared with no DMT or lower-efficacy DMTs, the risks of using at least some MS DMTs, especially those with greater immunosuppression, may be higher for older people with MS. Infections, cancers, and diminished responses to vaccinations are more common in older people but may be even higher in those with MS, particularly older people with MS who use specific classes of DMTs, especially cell-depleting agents such as anti-CD20 therapies (eg, ocrelizumab, rituximab, ofatumumab, and ublituximab) and the rarely used alemtuzumab and mitoxantrone.

Common comorbidities in older people with MS, such as diabetes mellitus, hypertension, vascular disease, and cancer, are associated with worse clinical outcomes in MS

 and may also worsen safety outcomes and contribute to early discontinuation of MS DMTs.

 Thus, clinical equipoise appears to be achieved in the discussion about how, or whether, to use or discontinue DMTs in aging people with MS. The challenge is to balance DMT efficacy in relapses and disability progression with the risks of infections (in multiple drug classes), worsening vascular risks (as with sphingosine-1-phosphate [S1P] modulators), or malignancies (with S1P modulators and cell-depleting agents) in aging people with MS.

DMT Discontinuation in Older Adults With MS

At least 50 observational, retrospective, and cohort studies have examined outcomes after discontinuation of MS DMTs. Many are series of variable sizes, including all ages, many reasons for discontinuation, and DMTs with differing mechanisms of action. Others have specifically studied older patients, certain DMTs (especially fingolimod and natalizumab due to concerns of rebound disease activity with sequestering agents), or particular contexts such as pregnancy. Findings from these studies, as well as those from meta-analyses

 have concluded that the highest risk of MS relapse after DMT discontinuation is seen in younger people with MS, those with recent active disease (relapse or new MRI-detected lesions), and those with lower disability. Enhanced risk of disability progression upon DMT discontinuation is somewhat less clear but may be associated with older age, higher level of disability, and recent progression.

More recently, 5 randomized controlled trials (RCTs) have investigated disease activity recurrence risks in DMT discontinuation. Two have been published (DISCOMS [NCT03073603]

); 3 are ongoing (STOP-I-SEP [NCT03653273],

). In addition, 3 propensity-matched trials addressing DMT discontinuation have been published. See 

 for a comparison of study design (all 8 trials, Table 1) and primary outcomes (the 5 published studies, Table 2).

 enrolled 259 participants 55 years or older with no relapse for at least 5 years and no new MRI-detected lesions for at least 3 years. Participants were evenly divided into continuers and discontinuers and followed for a median of 24.5 months. The primary outcome of this rater-blinded study was a relapse or any new brain lesion. There were multiple secondary outcomes, including progression of disability confirmed at 6 months, and several patient-reported outcomes focused on quality of life, MS symptoms, and patient satisfaction. The statistical approach was a noninferiority analysis with an 8%
noninferiority margin.

The median age in DISCOMS was 63 years, and the average time since last relapse was almost 14 years. Findings from this study were unable to demonstrate noninferiority in the combined primary outcome measure, primarily due to a small increased risk of new brain MRI activity in discontinuers, especially 1 to 2 new asymptomatic lesions. Time to first event was also faster in the discontinuers. Relapses were rare in both groups, and there were no substantial differences in many other clinical measures and safety outcomes. Importantly, progression of disability confirmed at 6 months was very similar in continuers (11.1%) and discontinuers (12.3%). Patient satisfaction with treatment was the same in both groups at the outset but significantly higher among discontinuers at the end of the study. Notably, among discontinuers with new relapse or MRI activity, mean age was 60.8 years vs 63.3 years among discontinuers without new disease activity, and the number of years since disease onset since last relapse was also very similar in those discontinuers with and without new disease activity.

An extension of DISCOMS with 74 participants from the original study has also been completed and published.

 It was performed at the 10 largest recruiting sites and included those who completed at least 18 months in DISCOMS, did not meet the primary end point of relapse or new MRI-detected lesion, were willing to participate in 1 additional visit at least 1 year after the last DISCOMS visit, and remained in their original assignment group. The primary outcome was time to relapse or new brain MRI-detected lesion. One of 30 continuers and 2 of 44 discontinuers had new MRI-detected lesions, but there were no relapses in either group. As in the original DISCOMS trial, other clinical outcomes were minimally different between groups. Additionally, faster time to new disease activity (from the start of the primary study) and higher treatment satisfaction continued among discontinuers.

 was a similarly designed study but potentially included patients as young as 18 years. Participants had to be free of relapses and could have a single new MRI-detected lesion in the past 5 years prior to enrollment. The primary outcome measure was a new relapse or any significant new MRI activity, meaning 3 or more new brain T2 lesions or 2 or more contrast-enhancing brain MRI-detected lesions. The median age was 54 years, and median time from last relapse was approximately 9 years. This study was stopped prematurely after 89 of 150 (59.3%) anticipated participants were enrolled and followed for a median of 15.3 months, as there was significant new activity in the discontinuer group (8 of 45; 17.8%) vs none in the continuer group. Importantly, the median age of those with significant new disease activity was 46 years (mean, 49.5 years). When the outcome was assessed as in DISCOMS, new activity was 24.4% higher over a shorter follow-up time in DOT-MS vs 12.2% in DISCOMS. Thus, the DOT-MS participants were younger and had more recent disease activity at baseline than those in DISCOMS and had twice as much recurrent disease as discontinuers in DISCOMS. Disability progression was confirmed in 17% of continuers vs 16% of discontinuers in DOT-MS. Comparing the DOT-MS and DISCOMS data reinforces the idea that younger age and more recent disease activity are key risks for disease recurrence in those who discontinue DMT and suggests that although there may be no tipping point where disease recurrence is so low that all people with MS with characteristics similar to those of DISCOMS participants should strongly consider this option, the risks are low enough that discussions about discontinuation should be routine in people with MS fulfilling these criteria.

One significant limitation of some of the retrospective observational trials and both published RCTs examining DMT discontinuation in MS has been the lack of inclusion of more highly effective drugs, especially cell-trafficking agents such as fingolimod and natalizumab, which have been associated with significant return of disease activity upon discontinuation of DMT in younger patients. An interrogation of the OFSEP registry

 has addressed this through a propensity-matched study of 154 participants continuing and 154 participants discontinuing fingolimod, natalizumab, and anti-CD20 agents (mostly rituximab, a small number of ocrelizumab) combined, with a minimum 2-year follow-up. Importantly, these participants had a median age of 57.5 years, a median time since last relapse or new MRI-detected lesion of approximately 4 years, and significantly more disability than DISCOMS or DOT-MS participants. Moreover, more than 35% had 3 or more prior DMT failures. For those discontinuing fingolimod and natalizumab, there was faster time to relapse (both drugs) and progression of disability (significant only for natalizumab) compared with continuers, and this was not seen in the anti-CD20 DMT discontinuers. A similar German propensity-matched cohort of those continuing or discontinuing only ocrelizumab had a similar primary outcome, but there were discordant baseline features and a degree of new activity in both groups.

 The ages at time of discontinuation were not reported but, based on extrapolating from age at onset of ocrelizumab use and median time on the drug before discontinuation, appear to be in the mid-40s. The median Expanded Disability Status Scale score (2.5) and time since last relapse (3.4 years) suggest this group was younger and had less impairment overall at baseline compared with those in the OFSEP study. As in the OFSEP study, the time to new inflammatory activity (relapse or MRI-detected lesion) and PIRA was not faster in discontinuers (following a median of 28.3 months); however, there appeared to be substantially more PIRA in findings from the French study. This difference likely reflects the older French cohort with more disability, with a high number of people with SPMS on anti-CD20 agents. The German trial data also seemed to show that new disease activity in discontinuers began to exceed that in continuers at approximately 24 months, consistent with a potential slow wearing-off of benefit after 2 years. Interestingly, findings from a small, open-label trial looking at a 2-dose induction of ocrelizumab in recently diagnosed people with relapsing-remitting MS reported that 6 of 19 participants had MRI-only disease reactivation starting at month 19 of observation.

 but with 4 doses of ocrelizumab is underway and should be completed in 2030.

An alternative to the either/or method of stopping or continuing the same MS DMT in an older person with MS might be risk reduction by de-escalation, especially for people who have been receiving infrequently administered and highly effective (but potentially riskier) agents for long periods. De-escalation would be based on the principle that prolonged use of highly effective DMTs may not be indicated or offer enhanced benefit

 due to an overall decline in MS disease activity with age, especially when risks are likely higher with some more highly effective DMTs in older individuals.

 De-escalation might be accomplished by reducing the dose

 of the current medication or switching to an alternative with lower risks.

 De-escalation might also be a useful strategy for those taking fingolimod or natalizumab to hopefully avoid disease recurrence or rebound with abrupt discontinuation. The information base for de-escalation is rapidly evolving, but as of yet, there is no broadly accepted algorithm or strategy for implementation and there are minimal data specifically in older people with stable MS.

Future DMT RCTs should include adequate subgroups of participants older than 55 years to ascertain more completely the benefits and hazards associated with DMT use in this population. Similarly, treatment discontinuation algorithms

 based on presently available data offer the opportunity to design RCTs examining different approaches. It will be especially important to define the long-term consequences of modest silent MRI activity after discontinuation of MS DMTs.

 Development of postdiscontinuation, patient-specific recurrence risk profiles with machine learning would aid decision-making in the office. Present data

 do not suggest that analyzing serum biomarkers (eg, serum neurofilament light chain and glial fibrillary acidic protein) at the time of DMT discontinuation is predictive of disease recurrence, but this approach should be pursued further and measurements should be made longitudinally following discontinuation. Finally, DMT utility in those older than 55 years and those with LOMS needs to be examined in more detail.

Among people with MS older than 55 years, there is a relative dearth of data, one way or the other, arguing that presently available MS DMTs have a positive risk-benefit ratio. Subgroup analyses from phase 3 clinical trials, with the limitation of including only a few participants older than 55 years, argue that there is minimal benefit for those 55 years or older, especially if there is no recent relapse or active MRI-detected lesion activity. In older people with MS who discontinue DMT, findings from observational studies and RCTs also show that the highest risk of recurrence of MS activity is in relatively younger patients with recent disease activity. However, even among people with MS older than 60 years with long-time stable disease, available data suggest that a small risk of recurrent MS activity upon DMT discontinuation remains, especially modest new MRI activity of unclear long-term clinical significance. The risk of stopping agents such as fingolimod and natalizumab in this older group with stable disease may also be higher, though this is less clear.

As a real-world example, the regimen at the University of Colorado, Aurora, for people with stable MS older than 60 years who discontinue DMT, especially DMT not associated with rebound activity, is to examine them every 6 months and schedule brain MRI scans once a year for 2 years. Assuming 2 years of stable examination and MRI scan results, we then transition to annual examinations and MRI scans every other year until they are 65 years or older, based on discussions
with them.

Based on all available data, older people with MS may stay on their DMT if tolerated, accept some slight enhanced risk of disease recurrence with DMT discontinuation, or consider de-escalation to a DMT with lower risk, especially if they are not tolerating their present DMT or if they have had recent MS disease activity. In all 3 scenarios, ongoing monitoring for new disease activity remains a key component of MS care.

Goyne CE, Fair AE, Sumowski PE, Graves JS. The impact of aging on multiple sclerosis. 

Tremlett H, Zhao Y, Joseph J, Devonshire V; UBCMS Clinic Neurologists. Relapses in multiple sclerosis are age- and time-dependent. 

. 2008;79(12):1368-1374. doi:10.1136/jnnp.2008.145805

Coerver EM, Kaçar S, Ciccarelli O, et al. Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations. 

. 2024;30(10):1296-1308. doi:10.1177/13524585241272938

Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. 

. 2022;145(9):3147-3161. doi:10.1093/brain/awac016

Lassmann H. Pathogenic mechanisms associated with different clinical courses of multiple sclerosis. 

. 2019;9:3116. doi:10.3389/fimmu.2018.03116

Albelo-Martínez M, Rizvi S. Progressive multiple sclerosis: evaluating current therapies and exploring future treatment strategies. 

. 2025;22(4):e00601. doi:10.1016/j.neurot.2025.e00601

Wallin MT, Culpepper WJ, Campbell JD, et al; US Multiple Sclerosis Prevalence Workgroup. The prevalence of MS in the United States: a population-based estimate using health claims data. 

. 2019;92(10):e1029-e1040. doi:10.1212/WNL.0000000000007035

Signori A, Schiavetti I, Gallo F, Sormani MP. Subgroups of multiple sclerosis patients with larger treatment benefits: a meta-analysis of randomized trials. 

. 2015;22(6):960-966. doi:10.1111/ene.12690

Capanna M, Signori A, Sormani MP. Is the effect of drugs in progressive MS only due to an effect on inflammation? a subgroup meta-analysis of randomised trials. 

. 2022;28(11):1744-1751. doi:10.1177/13524585221094944

Zhang Y, Gonzalez Caldito N, Shirani A, et al. Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials. 

. 2020;13:1756286420969016. doi:10.1177/1756286420969016

Fernández Ó, Sörensen PS, Comi G, et al. Managing multiple sclerosis in individuals aged 55 and above: a comprehensive review. 

. 2024;15:1379538. doi:10.3389/fimmu.2024.1379538

Weideman AM, Tapia-Maltos MA, Johnson K, Greenwood M, Bielekova B. Meta-analysis of the age-dependent efficacy of multiple sclerosis treatments. 

. 2017;8:577. doi:10.3389/fneur.2017.00577

Zhang Y, Salter A, Jin S, et al. Disease-modifying therapy prescription patterns in people with multiple sclerosis by age. 

. 2021;14:17562864211006499. doi:10.1177/17562864211006499

Cisternas M, Bartolome L, Gitar B, et al. Health care resource utilization and disease modifying treatment use in multiple sclerosis patients by age and insurance type. 

. 2021;37(4):597-604. doi:10.1080/03007995.2021.1885367

Goereci Y, Ellenberger D, Rommer P, et al. Persons with multiple sclerosis older than 55 years: an analysis from the German MS registry. 

. 2024;271(6):3409-3416. doi:10.1007/s00415-024-12286-4

McGinley MP, Cola PA, Fox RJ, Cohen JA, Corboy JJ, Miller D. Perspectives of individuals with multiple sclerosis on discontinuation of disease-modifying therapies. 

. 2020;26(12):1581-1589. doi:10.1177/1352458519867314

Naseri A, Nasiri E, Sahraian MA, Daneshvar S, Talebi M. Clinical features of late-onset multiple sclerosis: a systematic review and meta-analysis. 

. 2021;50:102816. doi:10.1016/j.msard.2021.102816

Robin C, Rollot F, Lefort M, et al; OFSEP Investigators. Use of disease-modifying therapies in patients with late-onset multiple sclerosis. 

. 2025;105(3):e213744. doi:10.1212/WNL.0000000000213744

Prosperini L, Haggiag S, Tortorella C, Galgani S, Gasperini C. Age-related adverse events of disease-modifying treatments for multiple sclerosis: a meta-regression. 

. 2021;27(9):1391-1402. doi:10.1177/1352458520964778

Salter A, Lancia S, Kowalec K, Fitzgerald KC, Marrie RA. Comorbidity and disease activity in multiple sclerosis. 

. 2024;81(11):1170-1177. doi:10.1001/jamaneurol.2024.2920

Salter A, Lancia S, Kowalec K, Fitzgerald K, Marrie RA. Comorbidities, safety and persistence in phase III clinical trials in multiple sclerosis. 

. 2025;96(11):1070-1076. doi:10.1136/jnnp-2024-335710

Prosperini L, Haggiag S, Ruggieri S, Tortorella C, Gasperini C. Stopping disease-modifying treatments in multiple sclerosis: a systematic review and meta-analysis of real-world studies. 

. 2023;37(10):915-927. doi:10.1007/s40263-023-01038-z

Shahid S, Hasan A, Iqbal M, et al. Discontinuation of disease-modifying therapy in stable multiple sclerosis: a systematic review and meta-analysis. 

. 2025;101:106599. doi:10.1016/j.msard.2025.106599

Androdias G, Lünemann JD, Maillart E, et al. De-escalating and discontinuing
disease-modifying therapies in multiple sclerosis. 

. 2025;148(5):1459-1478. doi:10.1093/brain/awae409

Corboy JR, Fox RJ, Kister I, et al; DISCOMS Investigators. Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial. 

. 2023;22(7):568-577. doi:10.1016/S1474-4422(23)00154-0

Coerver EME, Fung WH, de Beukelaar J, et al. Discontinuation of first-line
disease-modifying therapy in patients with stable multiple sclerosis: the DOT-MS randomized clinical trial. 

. 2025;82(2):123-131. doi:10.1001/jamaneurol.2024.4164

Disease modifying therapies withdrawal in inactive secondary progressive multiple sclerosis patients older than 50 years (STOP-I-SEP) (STOP-I-SEP). ClinicalTrials.gov. Updated March 30, 2026. Accessed July 21, 2026. https://clinicaltrials.gov/study/NCT03653273

Disease modifying therapies withdrawal in inactive relapsing-remitting multiple sclerosis patients aged 55 and over (TWINS : therapies withdrawal in relapsing multiple sclerosis) (TWINS). ClinicalTrials.gov. Updated January 3, 2025. Accessed July 21, 2026. https://clinicaltrials.gov/study/NCT06663189

Ocrelizumab discontinuation in relapsing multiple sclerosis (AMS05).
ClinicalTrials.gov. Updated June 23, 2026. Accessed July 20, 2026. https://clinicaltrials.gov/study/NCT05285891

Corboy JR, Fox RJ, Cutter G, et al. Discontinuation of disease-modifying therapies in MS: the DISCOMS extension trial. 

. 2025;31(2):159-173. doi:10.1177/13524585241303489

Jouvenot G, Courbon G, Lefort M, et al; OFSEP Investigators. High-efficacy therapy discontinuation vs continuation in patients 50 years and older with nonactive MS. 

. 2024;81(5):490-498. doi:10.1001/jamaneurol.2024.0395

Konen FF, Axhausen F, Wolff S, et al. Discontinuation of ocrelizumab in multiple sclerosis: reoccurrence of disease activity. 

. 2026;97(6):513-521. doi:10.1136/jnnp-2025-337944

Salazar-Camelo A, Vega L, Fadlallah Y, et al. Finite-course ocrelizumab in relapsing multiple sclerosis: results of two prospective open-label trials with matched controls. 

. 2025;31(11):1338-1347. doi:10.1177/13524585251375350

Vollmer BL, Wolf AB, Sillau S, Corboy JR, Alvarez E. Evolution of disease modifying therapy benefits and risks: an argument for de-escalation as a treatment paradigm for patients with multiple sclerosis. 

. 2022;12:799138. doi:10.3389/fneur.2021.799138

Gross RH, Corboy J. De-escalation and discontinuation of disease-modifying therapies in multiple sclerosis. 

. 2024;24(9):341-353. doi:10.1007/s11910-024-01355-w

Selmaj K, Hartung HP, Mycko MP, Selmaj I, Cross AH. MS treatment de-escalation: review and commentary. 

. 2024;271(10):6426-6438. doi:10.1007/s00415-024-12584-x

Disanto G, Ripellino P, Riccitelli GC, et al. De-escalating rituximab dose results in stability of clinical, radiological, and serum neurofilament levels in multiple sclerosis. 

. 2021;27(8):1230-1239. doi:10.1177/1352458520952036

Starvaggi Cucuzza C, Longinetti E, Ruffin N, et al. Sustained low relapse rate with highly variable B-cell repopulation dynamics with extended rituximab dosing intervals in multiple sclerosis. 

. 2022;10(1):e200056. doi:10.1212/NXI.0000000000200056

Foley JF, Defer G, Ryerson LZ, et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial. 

Sacco R, Disanto G, Pravatà E, et al. De-escalation from anti-CD20 to cladribine tablets in multiple sclerosis: a pilot study. 

. 2024;92:106145. doi:10.1016/j.msard.2024.106145

Siddiqui A, Hua LH. Impact of age on switching or stopping disease modifying therapies in multiple sclerosis. 

. 2025;22(4):e00603. doi:10.1016/j.neurot.2025.e00603

Hedström AK. Should disease-modifying therapy be discontinued in older patients with stable MS after long-term clinical and radiological stability? commentary. 

. 2025;31(7):769-770. doi:10.1177/13524585251344786

Fox RJ, Cree BAC, de Sèze J, et al. Temporal relationship between serum neurofilament light chain and radiologic disease activity in patients with multiple sclerosis. 

. 2024;102(9):e209357. doi:10.1212/WNL.0000000000209357

Bose G, Healy BC, Saxena S, et al. Increasing neurofilament and glial fibrillary acidic protein after treatment discontinuation predicts multiple sclerosis disease activity. 

. 2023;10(6):e200167. doi:10.1212/NXI.0000000000200167

Risks and Benefits of Disease-Modifying Therapies  in People Aging With Multiple Sclerosis

Older adults with multiple sclerosis (MS) experience challenges across multiple aspects of health care, and health care delivery must evolve to meet the geriatric needs of the aging MS population. Although the literature on multidisciplinary care or access to care for older adults with MS is sparse, the geriatric care literature for the general population highlights the importance of comprehensive geriatric assessment and the barriers to health care. This review, based on a 2024 Consortium of MS Centers’ Consensus Statement committee meeting, discusses multidisciplinary care and key barriers to care for older adults with MS and integrates insights from the broader geriatric care literature. Clinical and policy-level recommendations are shared to enhance provider knowledge, improve care delivery, and support better outcomes for older adults living with MS.

From the Department of Neurological Sciences, University of Nebraska, Omaha, NE (RStewart); Independence Care System, Brooklyn, NY (RStacom); BronxCare Multiple Sclerosis Center, Bronx, New York (RStacom); Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Neurology, University of Colorado Anschutz School of Medicine, Aurora, CO (JB); UCHealth Yampa Valley Medical Center, Steamboat Springs, CO (PB); Department of Neurology, Georgetown University Medical Center, Washington, DC, (JW); Department of Neurosciences, University of California San Diego, San Diego, CA (JSG); private practice, Greensboro, NC (MDB); Departments of Internal Medicine and Geriatrics, University of Nebraska Medical Center, Omaha, NE (MTC); Department of Neurology, University of Colorado Anschutz School of Medicine, Aurora, CO (JRC); departments of Medicine and Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada (RAM); Nova Scotia Health, Halifax, Nova Scotia, Canada (RAM); Department of Clinical Neurology, Johns Hopkins School of Medicine, Baltimore, MD (SDN); Department of Neurology, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV (LHH); Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (SAM); Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY (FWF); Multiple Sclerosis Center, Holy Name Medical Center, Teaneck, NJ (FWF); Division of MS/Neuroimmunology, The Ohio State University, Wexner Medical Center, Columbus, OH (YZ). 

Renee Stewart, APRN-DNP, 4242 Farnam St, Omaha, NE 68131; 

Renee Stewart, DNP, APRN, has been on an advisory board for Genentech. Rachael Stacom, NP, has served on advisory boards for Genentech and TG Therapeutics. Jacquelyn Bainbridge, PharmD, has served on advisory boards for EMD-Serono, Novartis, and TG Therapeutics. Jeff Wilken, PhD, has been a speaker for Biogen, EMD Serono, and Sanofi; a paid consultant for Bayer and Sanofi; and has received research funding from Biogen and Sanofi. John R. Corboy, MD, MA, has received compensation as the medical director of the Rocky Mountain MS Center and associate editor of the 

. He has received research support from EMD Serono, the National Institutes of Health via the Immune Tolerance Network, and the National Multiple Sclerosis Society. Ruth Ann Marrie, MD, PhD, FRCPC, receives research funding from the Arthritis Society, the Canadian Institutes of Health Research, Children’s Hospital Research Institute of Manitoba, Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Manitoba Medical Service Foundation, MS Canada, National Multiple Sclerosis Society, Pfizer Foundation, Public Health Agency of Canada, and the US Department of Defense. She is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada, and holds the Gillian Hope Multiple Sclerosis Clinical Research Chair (Dalhousie University). Le H. Hua, MD, has received personal fees for speaking, consulting, and advisory board activities from Alexion, EMD Serono, Genentech, Genzyme, Horizon, Novartis, and TG Therapeutics, and has had research support paid to her institution from Genentech outside the submitted work. Frederick W. Foley, PhD, has been on advisory boards for Bayer and Biogen; has been a paid consultant for Biogen; and has been a speaker for EMD Serono and Sanofi. Authors Patty Bobryk, MHS, PT, MSCS, ATP; Jennifer S. Graves, MD, PhD, MAS; Mona D. Bostick, RDN, LDN; Maureen T. Choman, MD; Scott D. Newsome, DO, MSCS; Sarah A. Morrow, MD, FRCPC, MS; and Yinan Zhang, MD, have declared no relevant disclosures.

 This manuscript stems from presentations and discussions at the Consortium of Multiple Sclerosis Centers’ (CMSC) Aging and MS Consensus Conference held June 1 and 2, 2024, and is based on the CMSC publication “MS and Aging: A Summary Statement from a CMSC Consensus Conference.”

Multidisciplinary care for older adults with multiple sclerosis (MS) should address geriatric issues, which can be done using a comprehensive geriatric assessment by providers in disciplines including but not limited to neurology, geriatrics, rehabilitation, social work, pharmacy, neuropsychology, psychology/psychiatry, nutrition, urology, ophthalmology, and audiology.

Providers should assess for health care access issues such as structural and financial barriers in older adults with MS.

Recognition of health care disparities facing older adults with MS, such as ageism and ableism, can improve quality of care.

The most recent estimate of the prevalence of multiple sclerosis (MS) in the United States is approaching 1 million individuals, with the highest peak prevalence between the ages of 55 and 64 years, followed by the 65- to 74-year-old age group, suggesting an increasing number of aging individuals.

This partly reflectsthe advances in disease-modifying therapies (DMTs) and supportive care that have extended the life expectancy of individuals with MS.

 Older adults with MS often have unique health care needs and challenges arising from worsening disability, comorbid conditions, and socioeconomic vulnerabilities. These issues require a comprehensive multidisciplinary approach to achieve a high-quality level of care. At the same time, access to health care in general is a documented challenge for both the general aging population and people with MS. Limited research has examined the intersection of aging and MS regarding multidisciplinary care and access to care. In this review, we discuss the known benefits of geriatric multidisciplinary care and challenges in access to care for older adults with MS, identify similar concepts from the general aging population, and address opportunities for improvement. Although the majority of cited literature originates from the US, we also included studies from other countries to capture relevant international perspectives.

It is commonly accepted that multidisciplinary care is optimal for MS treatment, as advocated by both providers and patients.

 Older adults with MS experience unique issues related to aging and accumulating neurological disability, which require management by providers in disciplines including but not limited to neurology, geriatrics, rehabilitation, social work, pharmacy, neuropsychology, psychology/psychiatry, nutrition, urology, ophthalmology, and audiology (

 The Roles of Multidisciplinary Specialists in the Comprehensive Geriatric Assessment of Older Adults With Multiple Sclerosis

MS multidisciplinary care units integrate many of the aforementioned specialties,

 but they do not routinely perform a comprehensive geriatric assessment (CGA). In the primary care setting, integrated geriatric care has been shown to reduce medical costs and the number of prescription drugs used and to decrease the frequency of emergency department visits and hospitalizations of older adults who attended an integrated geriatric outpatient clinic compared with a nongeriatric clinic.

 Another study evaluating the effect of outpatient CGA-based care by a multidisciplinary team found improvements in frailty and mortality among older adults with multimorbidity.

Currently, no studies have adequately evaluated whether team-based comprehensive management improves MS health care utilization or neurological function outcomes. Improved health care utilization refers to measurable changes in how people with MS use health care services that reflect more effective, appropriate, and efficient care.

In other neurological conditions such as stroke, CGA was associated with decreased hospital mortality and patients receiving more rehabilitation intervention and home health care.

The results of a study by Bahri et al were encouraging. The study describes the implementation of a neurogeriatric MS clinic that provides same-day access to MS care, rehabilitation, nutrition, social work, pharmacy, and neuropsychology during a 4-hour clinic session for adults with MS aged 60 years or older.

 Providers in the clinic delivered a CGA covering functional capacity, cognition, mood, frailty, polypharmacy, nutrition, social/financial need, and goals of care. Recommendations were communicated to the patient, their neurologist, and their primary care physician. An initial survey of clinic participants reflected self-reported improvements in the quality of care.

Future research to evaluate the efficacy of multidisciplinary care in MS could include short-term measures such as the assessment of decision-making aligned with treatment guidelines and patient-reported outcomes, as well as long-term measures, such as assessment of DMT efficacy and safety and reducing claims for disability benefits.

 Additional areas of future research on multidisciplinary care for older adults with MS could include improving understanding of the perspectives of older adults with MS to align with their goals of care, developing pathways to implement CGA, methods to identify patients who benefit from such care, and evaluations of cost-effectiveness.

Penchansky and Thomas identified 5 dimensions of health care access: availability, accommodation, accessibility, affordability, and acceptability.

 Availability refers to the adequacy of the supply of services, including physicians, clinics, hospitals, and specialized programs, in relation to the needs and volume of clients. Accommodation focuses on how services are organized to meet client needs, such as appointment systems, hours of operation, walk-in options, and telephone services. Accessibility describes the geographic relationship between sites of services and client location, considering transportation, travel time, distance, and cost. Affordability is the cost of services relative to clients’ incomes, including insurance coverage, co-payments, and perceived value. Last, acceptability relates to a patient’s satisfaction with the delivery of equitable care. All of these affect the health care available to older adults with MS.

Individuals with MS who are aging often have complex and evolving health care needs, and addressing these needs requires access to coordinated, specialized care. MS is characterized by a high burden of chronic comorbidities, cognitive decline, and increasing physical disability

; these challenges increase with age. Disparities in access and quality of care are further influenced by social determinants of health, defined as the conditions in which people are born, grow, live, work, and age that affect health outcomes and contribute to inequities in disease progression, access to care, and quality of life

 Key Issues and Challenges to Health Care Access for Older Adults With MS

Older adults with MS highly value access to trusted health care providers with expertise in MS

; however, many individuals with MS in the US live in a 

, defined as living more than 60 miles from a neurologist. Specialist access particularly affects those in rural areas and in regions where there is a large number of people with disabilities who do not have insurance.

 A cross-sectional study of Medicare beneficiaries found that nearly 20% of those living with MS traveled 50 miles or more each way to access neurologic care, with older adults disproportionately affected.

 The shortage of MS clinicians is further exacerbated by the limited availability of geriatricians, who provide value n managing the complex medical, cognitive, and psychosocial needs of aging individuals. While the US Department of Health and Human Services projects growth in the number of geriatricians, a projected shortfall of nearly 27,000 physicians remains concerning, especially in rural areas, where only approximately 10% of geriatricians currently practice.

A 2015 systematic review of cross-sectional studies found that individuals with MS commonly experience a high burden of comorbidities.

 The prevalence of many of these comorbid conditions increases with age, including hypertension, hyperlipidemia, diabetes, ischemic heart disease, cerebrovascular disease, and chronic lung disease. This age-related rise in comorbidity burden was most recently described in a meta-analysis of 14 clinical trials that included over 17,000 individuals with MS. The study reported that people with MS over the age of 50 were 5 times more likely to be diagnosed with hypertension compared with those between 30 and 40 years of age.

The cohort of individuals aged 50 years or older was also 3.5 times more likely to be diagnosed with diabetes and 5 to 6 times more likely to have ischemic heart disease and cerebrovascular disease.These individuals tend to be high utilizers of health care services and face increased risks of adverse health outcomes, underscoring the need for improved, coordinated systems of care.

In the general aging population, cognitive impairment also plays a pivotal role in shaping health care access.Between 12% and 18% of US adults over age 60 have mild cognitive impairment. These individuals often have difficulty managing appointments, using telehealth platforms, advocating for themselves, and conveying accurate medical histories.

Cognitive deficits are well documented in people with MS and have a greater association in those of both older age and higher levels of disability. These overlapping factors may contribute to a compounding effect, further limiting health care access and exacerbating challenges as individuals with MS age.

Older adults with MS often face transportation challenges. Chiu et al reviewed barriers to the accessibility and continuity of health care services for people with MS and highlighted that transportation barriers significantly impact their ability to attend medical appointments, which can lead to delays in care and potential deterioration of health outcomes.

 The study emphasized the need for health care systems to address these barriers by implementing more accessible transportation options and improving the overall accessibility of health care facilities to better serve people with MS.

 Similar studies among the general aging population show the same, as about 20% of older adults do not drive and up to one-third face driving restrictions.

 A qualitative study in rural communities identified 5 primary barriers to care, with limited transportation being the most prevalent. The additional barriers noted were limited health care supply (eg, fewer per capita hospital beds, doctors, nurses, and other health care services), lack of quality health care (eg, concerns about provider competence and service quality), social isolation, and financial constraints.

Income plays a critical role in determining an individual’s ability to address their health care needs. Limited financial resources can restrict access to essential services, including specialist visits, transportation, medications, assistive devices, and home- and community-based services. When looking at people with MS without distinguishing by age, direct medical costs (eg, doctor’s appointments and medications) are the biggest contributor to the high cost of MS. The cost of living with MS in the US is estimated to be $88,487 annually, and the average lifetime cost of care for a person with MS exceeds $4 million.

 The annual US economic burden (ie, the societal cost)—including individuals living with MS, the government (federal, state, and local), employers, health insurers, and more—is $85.4 billion.

We know that when the cost of health care becomes a significant financial burden, patients often forgo health care to afford other essential needs. A Canadian study showed that a cohort of older people with MS, who described themselves as financially challenged, prioritized housing, food, and transportation over their health care needs.

 In older adults living in the US, health-related quality of life was found to be significantly associated with household income.

Multidisciplinary care for older adults with multiple sclerosis should address geriatric issues, which can be done using a comprehensive geriatric assessment by providers in disciplines including but not limited to neurology, geriatrics, rehabilitation, social work, pharmacy, neuropsychology, psychology/psychiatry, nutrition, urology, ophthalmology, and audiology.

Volume 27, Issue Theme II

Risks and Benefits of Disease-Modifying Therapies in People Aging With Multiple Sclerosis

Aging and Multiple Sclerosis: Multidisciplinary Care and Access to Care

Comorbidity, Polypharmacy, and Aging in Multiple Sclerosis

Age-Related Changes in Multiple Sclerosis Pathophysiology and Clinical Function

From Disability to Capability: Trajectory of Healthy Aging From the Perspective of People With Multiple Sclerosis

Long-Term Changes in Patient-Reported Outcome Measures in People With Multiple Sclerosis 55 Years and Older: Analysis From the New York State Multiple Sclerosis Consortium

Letter From the Guest Editors - Multiple Sclerosis and Aging