As the population of individuals living with multiple sclerosis (MS) around the world continues to age, clinicians are faced with evolving and often complex challenges in managing these patients. While significant advances have been made in the treatment of relapsing MS (RMS), the needs of older patients require special attention. What considerations should physicians keep in mind when treating this patient population?
In many countries, older adults represent the largest age cohort among individuals with MS. This trend may be linked to improved life expectancy for MS patients, driven by advances such as improved healthcare approaches, including early therapy initiation, the use of high-efficacy disease-modifying treatments, advancements in symptomatic treatments and holistic treatment approaches. Additionally, the age of onset for MS has shifted forward, with cases diagnosed at age 50 or older categorised as late-onset MS (LOMS). There has been a notable rise in LOMS diagnoses, particularly among women. This increase may be attributed to greater awareness and improved diagnostic tools.
This shift in the age prevalence of the disease brings a host of considerations, as both MS itself and the immune system undergo significant changes with age. Understanding these shifts is essential to optimising care for this growing patient population.
The ageing immune system and its implications
Research has shown that as patients with MS get older, several key changes occur:
- A decline in magnetic resonance imaging (MRI) activity and relapse frequency, suggesting a reduced inflammatory disease burden
- An increased risk of progression, due to increased neurodegenerative processes or to less complete recovery from relapses
- A reduced efficacy of certain disease-modifying therapies (DMTs) beyond approximately 53 years of age, as predicted by regression models.
These shifts necessitate a reassessment of treatment approaches to ensure that therapeutic interventions continue to provide meaningful benefits while avoiding undue risks as best as possible.
Ageing is also associated with significant immunological changes, often referred to as ‘immunosenescence’, which can influence both the progression of MS and the response to treatment. Some of these changes include:
- A disproportionate increase in memory T cells that express more pro-inflammatory cytokines, which contributes to a shift in immune function, presenting with a non-specific inflammation
- A loss of ability to respond to new antigens, impacting overall immune resilience, including coping with infections and responding to vaccinations
- Persistent low-grade inflammation, under the term ‘inflamm-ageing’, which may exacerbate neurodegeneration and MS progression.
These changes present a unique challenge when determining the benefit-risk ratio of continuous immunosuppression in older adults with MS. Long-term immunosuppressive therapy is known to increase vulnerability to infections, necessitating a careful reevaluation of treatment strategies.
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