Late-Onset MS Linked to Lower Rates of Disease-Modifying Therapies

Fewer initiations and more frequent complete discontinuations were the primary drivers of patients with late-onset multiple sclerosis (LOMS) being less likely to be treated with disease-modifying therapies (DMTs) compared with patients with adult-onset MS (AOMS), according to a new study published in Neurology.¹

An increase in diagnoses of MS at older ages has led to an increase in diagnoses of LOMS,² where patients are diagnosed between ages 50 and 55 years. These cases make up approximately 5% to 12% of all cases of MS.³ Despite the significant number of cases, it is not well-known which strategy to take for treatment, especially compared with younger patients. The current study aimed to evaluate the difference in the use of DMT between patients with LOMS and AOMS in patients with MS in France.¹

Data from the Observatoire Français de la Sclérose en Plaques were used for this study, and data from January 1, 1997, through December 31, 2023, for patients with definite MS with relapse-remitting onset were included in the study. Demographic and clinical data were both collected through the last available patient visit; race and ethnicity were not recorded. DMTs and highly effective DMTs (HEDMTs) were identified for this study, and the reasons for discontinuation of any DMT or HEDMT were reported. The primary outcome was the annual probability of receiving a DMT for either patients with AOMS or LOMS from 1997 through 2023. The annual probability of receiving an HEDMT from 2008 to 2023 acted as the secondary outcome.

There were 36,148 patients with relapsing-onset MS who were included in the study; 2308 of the participants were aged 50 years or older at the time of disease onset. The median (IQR) follow-up was 10.8 (5.6-17.0) years, and patients with LOMS had a lower relapse rate during the follow-up compared with patients with AOMS.

A lower annual probability of receiving a DMT was found in patients with LOMS compared with AOMS (predicted probability, 73.7% vs 83.1%; OR, 0.57; 95% CI, 0.52-0.62). HEDMTs were also less likely to be prescribed to patients with LOMS compared with AOMS (predicted probability, 24.6% vs 44.4%) in the 2008 through 2023 period. A linear decrease in probability from ages 20 to 40 was found for the annual probability of being prescribed a DMT. A reduction of 10 percentage points per decade in probability was found for the probability of being prescribed an HEDMT.

Patients with LOMS were more exposed to teriflunomide, less exposed to fumarate and S1PR-modulator, and equally exposed to interferon and glatiramer acetate compared with patients with AOMS. Patients with LOMS had a lower rate of initiation of DMT compared with AOMS (0.13 vs 0.17 per patient year). There was no significant difference in the frequency of follow-up between the 2 groups.

The median duration on DMT was longer in patients with LOMS compared with those on AOMS (3.92 years vs 3.00). Rates of discontinuations were similar when excluding discontinuations due to pregnancy (59.7% in LOMS vs 60.4% in AOMS). Deescalation from HEDMT was also similar between the 2 groups (2.2% vs 2.1%, respectively).

There were some limitations to the study. Some age-related factors could influence the prescription of DMTs but were not evaluated in this study, including patient comorbidities, polypharmacy, cognitive status, socioeconomic status, social support, and patient preferences. The reason for discontinuation of DMTs requires more research to account for the decision-making process. Measurements were frequently missed. A specific analysis of the use of cladribine was not possible due to the limited accessibility in France. External validity of the results could be limited.

The researchers concluded that, at similar levels of disease severity, patients with LOMS were less likely to be treated with a DMT.

“Individual assessment of the risk/benefit ratio in each patient must be carefully addressed to avoid therapeutic inertia in patients with LOMS, and further studies are needed to clarify optimal treatment duration and exit strategies in this older population,” they concluded.

References

1. Gavoille A, Kerbrat A, Edan G, et al. Differences in use of disease-modifying therapies between patients with late-onset and adult-onset relapsing-remitting multiple sclerosis. Neurology. 2026;106:e214943. doi:10.1212/WNL.0000000000214943
2. Cicero CE, Chisari C, Salafica G, et al. Incidence of late onset multiple sclerosis in Italy: a population-based study. Sci Rep. 2024;14:29649. doi:10.1038/s41598-024-81284-3
3. Mouresan EF, Mentesidou E, Berglund A, McKay KA, Hillert J, Iacobaeus E. Clinical characteristics and long-term outcomes of late-onset multiple sclerosis. Neurology. 2024;102:e208051. doi:10.1212/WNL.0000000000208051