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February 22, 2026Journal of Neurology0 citationsOpen Access

Disability progression in multiple sclerosis: a latent class analysis of predictors

JGJie GuoTOTomas OlssonLALars Alfredsson

Key Result

Baseline clinical and lifestyle factors including older age, higher baseline EDSS, more early relapses, obesity, smoking, low sun exposure, and low physical activity were associated with unfavorable disability progression trajectories in relapsing-onset MS over 15 years.

Key Points

  • The aim was to identify patterns of disability progression in multiple sclerosis and their influencing factors.
  • Applied latent class trajectory modeling to EDSS data from newly diagnosed MS cases.
  • Collected baseline demographics, clinical, and lifestyle data at diagnosis.
  • Used multivariate logistic regression to explore associations with trajectory group membership.
  • Employed Kaplan-Meier analysis to evaluate time to confirmed disability worsening.
  • Identified seven distinct trajectories of EDSS disability progression.
  • Most common trajectory characterized by stable, low disability.
  • Older age, higher EDSS scores, frequent relapses, and comorbidities linked to unfavorable progression.
  • Obesity, smoking, and low sun exposure associated with worse outcomes.
  • High physical activity correlated with decreased odds of unfavorable progression.

Study Design

Type

Observational (n=3,163)

Multicenter

Yes

Structured PICO

Do baseline clinical and lifestyle factors predict long-term disability progression trajectories in newly diagnosed relapsing-onset multiple sclerosis?

P
Population
3,163 individuals with newly diagnosed relapsing-onset multiple sclerosis (MS) from the Swedish Epidemiological Investigation of MS (2005–2019), mean age at diagnosis 33.9 years, 71.6% female.
O
Outcome
Trajectory membership (patterns of disability progression over time based on repeated Expanded Disability Status Scale [EDSS] measurements)

Early clinical factors and modifiable lifestyle factors, such as obesity, smoking, and physical activity, are significantly associated with long-term disability progression trajectories in newly diagnosed relapsing-onset multiple sclerosis.

Limitations

  • Observational design limits causal inference
  • Lifestyle data self-reported at single time point, potential recall bias
  • Possible residual confounding despite adjustments
  • Exclusion of progressive-onset MS limits generalizability
  • Classification uncertainty in smaller trajectory groups
  • Potential selection bias due to exclusion of patients with fewer EDSS measurements
  • Lifestyle data based on self-report at a single time point (potential recall bias)
  • Non-randomized observational design limits causal interpretation
  • Potential reverse causation (e.g., physical activity and sun exposure)
  • Residual confounding by indication for treatment
  • Exclusion of individuals without repeated EDSS assessments may introduce selection bias
  • Findings may not be generalizable to progressive-onset MS or other settings

Abstract

Abstract Background Multiple sclerosis (MS) is a heterogeneous disease with highly variable long-term outcomes. We aimed to identify patterns of disability progression and their determinants to improve individualized risk assessment and support clinical decision-making. Methods We applied latent class trajectory modeling to Expanded Disability Status Scale (EDSS) data from 3163 newly diagnosed relapsing-onset MS cases in the Swedish Epidemiological Investigation of MS (2005–2019). Baseline demographics, clinical, and lifestyle data were collected at diagnosis, and participants were followed through the Swedish MS registry. Multivariate logistic regression was used to examine associations between baseline characteristics and trajectory group membership. Kaplan–Meier analysis estimated time to confirmed disability worsening, EDSS 3 and EDSS 4 across trajectory groups. Results Seven distinct EDSS trajectories were identified. Group 4 ( n = 1149) was the most common and characterized by stable, low disability. Groups 5–7 showed steadily increasing disability and were categorized as unfavorable ( n = 662). In multivariate models, older age at diagnosis, longer baseline disease duration, higher baseline EDSS score, more frequent early relapses, poor cognitive performance, and autoimmune comorbidities were associated with unfavorable progression. Among lifestyle factors, obesity, smoking, and low sun exposure were linked to worse outcomes, while high physical activity decreased the odds of unfavorable progression. No significant association was observed for baseline vitamin D levels. Time to confirmed disability progression outcomes differed substantially across trajectory groups. Discussion Early clinical and lifestyle factors were associated with long-term outcomes. These findings illustrate the heterogeneity of MS progression and support further investigation of early modifiable factors influencing long-term outcomes.

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Cite This Study

Guo et al. (2026) conducted an observational in relapsing-onset multiple sclerosis (n=3,163). N/A (observational study) was evaluated on trajectory group membership based on longitudinal EDSS progression patterns. Baseline clinical and lifestyle factors including older age, higher baseline EDSS, more early relapses, obesity, smoking, low sun exposure, and low physical activity were associated with unfavorable disability progression trajectories in relapsing-onset MS over 15 years.

synapsesocial.com/papers/699a9dae482488d673cd3c51https://doi.org/10.1007/s00415-026-13704-5
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