Worldwide, nearly half of people living with multiple sclerosis (MS) are aged over 50 [1]. In parallel, late-onset MS (LOMS), defined as MS having clinical onset after age 50, now represents almost 10% of diagnoses [2]. This increase – from around 1% in the 1990s – has been observed mainly in women [3].
Despite groundbreaking advances in MS therapy, treatment in older patients remains challenging: disease-modifying therapies (DMTs) primarily target relapsing inflammatory activity, which is less prominent in older individuals [4,2]. DMTs remain effective in older people with MS, despite a reduced overall clinical impact at the population level [1]. At the same time, age-related risks – particularly infections – increase, further complicating the risk-benefit balance [1].
As a result, the clinical management of ageing MS population must be adapted to better address age-related challenges [1].
“Raising awareness about the treatment of older individuals with MS has become increasingly important,” says Professor Anneke Van Der Walt from Monash University. “We are facing two key challenges. First, many people who were diagnosed with MS in their 20s or 30s are now ageing. Second, some individuals are being newly diagnosed in their 50s or even 60s, a group we refer to as very late-onset MS. Each of these populations requires specific consideration when it comes to treatment approaches and therapeutic decision-making.”
When to Stop? Treatment Discontinuation in Older People With MS
Deciding whether to continue or change therapy in older people with MS is complex, especially in the context of limited evidence [1]. People over 60 years of age with stable disease – characterised by prolonged relapse-free periods and no MRI (magnetic resonance imaging) activity for at least 3-5 years – are less likely to experience a relapse after discontinuation [5]. The DISCOMS trial indicated that stopping DMTs may be a reasonable option for people with MS aged over 55 years with stable disease [6]. However, 16 of 131 participants still had new or expanding brain MRI lesions [6]. An increased risk of relapse has been reported in individuals aged 50 years and older with high levels of disability and nonactive MS who stopped treatment – particularly natalizumab and fingolimod [7,1].
Professor Van Der Walt tells us, “An important question, particularly for people ageing with MS, is when treatment can be safely stopped or whether it is appropriate to switch from highly effective therapies – such as ocrelizumab or natalizumab – to treatments with a lower efficacy but potentially better long-term safety profile. These alternatives may be associated with less immunosuppression and fewer effects on the immune system. This question has been the focus of several studies published in recent years, including the DISCOMS trial [6]. Since then, several additional studies – including both real world studies and clinical trials – have explored this topic. The consistent message is that, for most older people with MS, complete treatment discontinuation is associated with disease reactivation, with new MRI lesions and, in some cases, clinical relapses. This risk appears to be particularly pronounced in individuals previously treated with natalizumab or fingolimod, where disease reactivation can be severe [7]. These observations highlight the need for a personalised approach that considers the specific therapy the individual is receiving. Rather than complete cessation, the question increasingly becomes whether treatment de-escalation may represent a safer and more appropriate strategy. Can we go from a highly effective treatment to a lower efficacy treatment? A prospective real-world experience was conducted in Germany and presented at ECTRIMS 2025 by Dr Axhausen. The study showed that switching from high-efficacy therapies to cladribine can maintain disease control in people over the age of 50. These early observations suggest that disease control may be maintained with lower-efficacy treatments in older people with MS. However, further research is needed, as the available observations largely come from real world evidence data set, and robust clinical trial evidence is still lacking.”
When MS Begins Later in Life
When MS begins later in life (after 50 years old), it tends to follow a more progressive course, driven mainly by neurodegeneration rather than frequent inflammatory activity. This has important implications for how MS is assessed and treated in older people [4,8].
“The available evidence remains limited, as this topic has only recently begun to attract broader interest,” says Professor Anne Kerbrat from the CHU de Rennes. “In a retrospective study published last year involving 881 patients from the French MS registry, a significantly longer time to first relapse and to first MRI activity was observed in treated individuals with LOMS compared with those who had not yet received DMTs, with no clear effect on disability progression [9]. Another key question concerns which treatments should be used today in patients with LOMS. This is also not an easy question to answer, as these individuals face a higher risk of side effects and have more comorbidities than younger people. It remains a very open question, and treatment decisions will likely need to be tailored to each individual patient, considering their clinical profile and comorbidities. Therapeutic inertia – hesitating to initiate treatment in patients who could still benefit from therapy – also represents an issue in late-onset MS.”
A nationwide study based on the Swedish MS registry shows that, although most individuals with LOMS receive DMTs, they are treated less frequently than those with adult-onset MS (74.7% vs 95.6%) [10]. People with LOMS are also less likely to receive high-efficacy DMTs and tend to reach significant disability earlier [8].
These insights underscore the urgent need to rethink and develop treatment strategies better suited to older people living with MS.
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Written by Stefania de Vito
Special thanks to Professor Anne Kerbrat (CHU de Rennes) and Professor Anneke Van Der Walt (Monash University) for their insights.
References
[1] Van Der Walt A et al. Nat. Rev. Neurol. 2025; 21(8): 432-448.
[2] Foong YC et al. JNNP 2026; 97(1): 50-58.
[3] Prosperini L et al. JNNP 2022; 93(10): 1137-1139.
[4] Filippi M et al. Brain 2024; 147(11): 3665-3680.
[5] Bsteh G et al. Eur. J. Neurol. 2021; 28(5): 1609-1616.
[6] Corboy JR et al. Lancet Neurol. 2023; 22(7): 568-577.
[7] Jouvenot, G. et al. JAMA Neurol. 2024; 81: 490-498.
[8] Knowles S et al. Annals Neurol. 2024; 95(3): 471-486.
[9] Robin C et al Neurology 2025; 105(3): e213744.
[10] Mouresan EF et al. Neurology 2024; 102(6): e208051.