Treatment escalation and de-escalation in late-onset MS

Patients with late-onset multiple sclerosis (LOMS) should be managed differently than patients with adult-onset (AO) MS. Prof. Fredrik Piehl (Karolinska University Hospital, Sweden) talked about various treatment-related aspects that should be taken into consideration for the management of this specific group of patients.

“We see less inflammatory disease activity and fewer relapses in patients with LOMS than in patients with AOMS,” said Prof. Piehl [1]. “However, the consequences of a relapse may be worse in patients with LOMS and LOMS is associated with more evident neurodegeneration.”

Differences between older and younger patients with MS can also be seen in the benefit of disease-modifying treatments. The benefit from treatment in terms of relapse risk and disability progression appears to be less in patients over 40 years than in patients younger than 40 years [2,3]. From 53 years of age, there may be no benefit at all, a meta-analysis indicated [4]. “On the other hand, with older age, the therapeutic risk increases due to co-morbidities and perhaps more severe treatment-related adverse events,” added Prof. Piehl. Especially with anti-CD20 therapies, the risk of hospital-treated infections increases with longer treatment duration [5]. “Moreover, infections are more likely to have an impact on disability progression if a patient is older,” according to Prof. Piehl.

Results from the DISCOMS study suggested that it is probably safe to de-escalate therapy in a population of patients with a median age of 62 years [6]. However, in patients around 50–55 years of age it may not be safe to de-escalate therapy, findings from the DOT-MS trial revealed [7]. “The authors observed a significantly increased MRI activity in patients who discontinued therapy versus those who stayed on therapy,” clarified Prof. Piehl. He further explained that the de-escalation strategy depends on the disease-modifying therapy at hand. “With anti-CD20 therapies, there is no substantial risk of rebound after discontinuation, whereas natalizumab comes with an increased risk of rebound if this drug is stopped.”

Prof. Piehl emphasised that the initiation of a disease-modifying treatment at an advanced age should be based on inflammatory disease activity and not just on chronological age cut-offs. Finally, he mentioned that the choice of therapy should be based on an individualised benefit-risk analysis, taking inflammatory activity and co-existing risk factors into account.

1. Piehl F, et al. Escalation and de-escalation of treatments in late-onset multiple sclerosis. 10th EAN Congress, 29 June–2 July 2024, Helsinki, Finland.
2. Hutchinson M, et al. J Neurol. 2009;256(3):405-415.
3. Signori A, et al. Eur J Neurol. 2015;22(6):960-966.
4. Weideman AM, et al. Front Neurol. 2017;8:577.
5. Virtanen S, et al. J Neurol Neurosurg Psychiatry. 2024 May 14:jnnp-2023-333206.
6. Corboy JR, et al. Lancet Neurol. 2023;22(7):568-57
7. Coerver E, et al. Mult Scler. 2023;29:(3S)4–136.

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Posted on 25 July 202425 July 2024