Understanding Late-Onset Multiple Sclerosis: A Swedish Nationwide Study

Multiple Sclerosis (MS) is often thought of as a disease that strikes young adults, but what happens when the disease begins later in life? A recent study from Sweden, published in *Neurology* in 2024, sheds light on late-onset MS (LOMS), defined as MS with symptom onset at age 50 or older. The study compares LOMS to adult-onset MS (AOMS), where symptoms begin between ages 18 and 49, examining patient characteristics, treatment approaches, and how the disease progresses over time.

Key Findings:
* Prevalence of LOMS: Nearly 12% of MS cases in the study began after age 50, highlighting that LOMS is not uncommon.

* Faster Disability Progression: Individuals with LOMS experienced a more rapid progression of disability compared to those with AOMS. They reached significant disability milestones, measured by the Expanded Disability Status Scale (EDSS) scores of 4 and 6, more quickly.

* Primary Progressive MS (PPMS): LOMS patients were more likely to be diagnosed with PPMS (25.2%) compared to AOMS patients (4.5%).

* Less DMT Exposure: Patients with LOMS were less frequently prescribed disease-modifying therapies (DMTs) compared to those with AOMS (74.7% vs 95.6%). Furthermore, only 45.8% of LOMS patients were exposed to high-efficacy DMTs, compared to 73.5% of AOMS patients.

* Limited DMT Benefit: The study found limited evidence of a beneficial effect of DMTs on long-term disability in LOMS.

Diving Deeper into the Results:
The Swedish study used data from the Swedish MS registry (SMSreg), a nationwide registry that captures approximately 85% of all MS cases in Sweden. The researchers looked at data from 8,739 patients with MS who had symptom onset between 2001 and 2018 and at least two recorded EDSS scores.

Disability Progression: Disability progression was measured by assessing the time from MS onset to confirmed sustained EDSS scores of 4 and 6. An EDSS score of 4 indicates significant disability, limiting the ability to walk without aid, while a score of 6 indicates the need for a walking aid. The study found that the risk of reaching these disability milestones was significantly higher for LOMS patients.

DMT Use: DMTs are medications used to modify the course of MS, reducing the frequency and severity of relapses and slowing disability progression. The study categorized DMT exposure as none, modest-efficacy therapy only, high-efficacy therapy only, or both. Modest-efficacy DMTs included interferon beta, glatiramer acetate, teriflunomide, and dimethyl fumarate, while high-efficacy DMTs included natalizumab, rituximab, ocrelizumab, fingolimod, alemtuzumab, cladribine, daclizumab, and autologous hematopoietic stem cell transplantation (aHSCT).

Subgroup Analysis: When analyzing the data by disease course (RRMS and PPMS), the researchers found that the differences between LOMS and AOMS were greatest in the RRMS group. However, in the PPMS group, LOMS conferred the same risk of reaching an EDSS score of 4.0 but an increased risk of reaching an EDSS of 6.0, compared with PPMS-AOMS. This suggests that PPMS may behave similarly in both LOMS and AOMS patients.

Why This Matters:
This study highlights that LOMS is a distinct subgroup of MS patients with unique challenges. These patients experience a more rapid disability progression, are less likely to receive DMTs, and may not benefit from these therapies to the same extent as AOMS patients. Several factors may contribute to the unfavorable disease evolution in LOMS:

* Increased prevalence of comorbidities
* Diminished exposure to and efficacy of DMTs
* Age-associated neurodegenerative processes
* Immune senescence

The authors emphasize the need for close monitoring of LOMS patients and further research to understand the benefits of DMTs in older adults with MS. They call for clinical trials that include a wider age range to optimize treatment and care for LOMS patients.

Considerations and Future Directions:
The authors acknowledge some limitations of their study: * Differences in follow-up time between groups
* Lack of information on medication adherence
* The approach to MS pharmacologic treatment has shifted over the past 2 decades in Sweden, which may limit translation of the findings.
* Lack of information on comorbidities

Despite these limitations, this study provides valuable insights into LOMS and underscores the need for a personalized approach to managing MS in older adults. Future research should focus on identifying the factors that drive disability progression in LOMS and developing targeted therapies to improve outcomes for these patients.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

Reference:
Mouresan, E. F., Mentesidou, E., Berglund, A., McKay, K. A., Hillert, J., & Iacobaeus, E. (2024). Clinical characteristics and long-term outcomes of late-onset multiple sclerosis: a Swedish nationwide study. Neurology, 102(6), e208051.