Caution is needed when discontinuing DMT in individuals under 60

Findings from a retrospective Spanish study support a cautious approach to discontinuing disease-modifying treatment (DMT) in patients with multiple sclerosis aged 50–60 years. Discontinuation appears safer in patients >60 years of age, but even then, systematic MRI monitoring is still recommended.

The MS population is ageing: over half of all MS patients are now ≥50 years of age. The effectiveness of DMT declines with age, while the risk of adverse events increases. Discontinuing DMT is an option, but the optimal patient profile for this approach has yet to be established. Therefore, Dr René Carvajal (Vall Hebron University Hospital, Spain) and colleagues conducted a study to characterise DMT discontinuation (incidence, reason for) and compare inflammatory and neurodegenerative outcomes in patients who discontinued versus those who continued treatment [1]. They included patients with MS who were ≥50 years of age and had received DMT for ≥6 months between 1994 and 2024.

Among 3,197 older MS participants in the prospective cohort, 563 were eligible for inclusion. Patients on immune reconstitution therapies were excluded. Of the participants included, 113 (20%) discontinued therapy; the median age was 58 years, the median disease duration was 21 years, the median Expanded Disability Status Scale (EDSS) score was 5.5, and the median time free of inflammatory activity was 4.5 years. Baseline was set 6 months after treatment discontinuation. A propensity score of 6:1 was used to match the continuation and discontinuation groups.

Of these 113 participants, 82 (73%) stopped first-line therapies (mainly due to tolerability issues), 26 (23%) discontinued anti-CD20 treatment, and 5 (4%) stopped anti-trafficking therapy (in both groups primarily due to safety concerns/infections).

Results after a median follow-up of about 5 years were compared with those of 581 patients who continued therapy. In patients ≥50 years of age, discontinuation was associated with higher inflammatory activity, with the highest levels observed in those treated with anti-trafficking DMTs and the lowest in the anti-CD20 therapy users group. MRI activity was also higher, but did not translate into a clear clinical impact. In the discontinuation group, 19.2% of participants experienced relapses versus 14.1% in the continuation group (P=0.6); MRI activity was observed in 40.9% versus 17.9%, respectively (P<0.005).

The risks associated with discontinuation were attenuated in patients >60 years of age (P=0.027) and were not linked to disease stability or treatment duration. In patients >60 years of age, the likelihood of resuming therapy was 93% lower than in those 50–55 years of age. Dr Carvajal stressed that anti-trafficking therapies should not be withdrawn without a clear exit strategy.

1. Carvajal R, et al. Defining optimal profiles for treatment discontinuation in older MS patients. O006, ECTRIMS 2025 Congress, 24–26 September 2025, Barcelona, Spain.

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Posted on 25 November 202525 November 2025