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Original Investigation
March 18, 2019

Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades: A Nationwide Population-Based Cohort Study in Sweden

Author Affiliations
  • 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 2Cognizant Technology Solutions, Stockholm, Sweden
  • 3Kermanshah University of Medical Sciences, Kermanshah, Iran
  • 4Institute of Environmental Medicine, Unit of Biostatistics, Karolinska Institutet, Stockholm, Sweden
JAMA Neurol. 2019;76(6):665-671. doi:10.1001/jamaneurol.2019.0330
Key Points

Question  Has the risk of reaching disability milestones in multiple sclerosis changed over the last decade?

Findings  In this nationwide population-based cohort study of 7331 patients with multiple sclerosis diagnosed between 1995 and 2010, a significant 3% decrease per calendar year of diagnosis for the risk of sustained Expanded Disability Status Scale score (EDSS) 3.0, a significant 6% decrease for the risk of EDSS 4.0, and a significant 7% decrease for the risk of EDSS 6.0 among patients with relapsing-onset multiple sclerosis was found.

Meaning  The risk of reaching disability milestones decreased significantly over the last decade in patients with relapsing-onset multiple sclerosis in Sweden.


Importance  Clinicians’ experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before.

Objective  To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden.

Design, Setting, and Participants  A nationwide population-based retrospective cohort study. By April 2017, 12 512 patients with available information on demographics, MS phenotype, and date of MS onset and diagnosis were registered in the Swedish MS Registry of which 7331 patients with at least 2 recorded Expanded Disability Status Scale scores (EDSS) and diagnosed between January 1995 and December 2010 were included. No further exclusion criteria were applied. Patients were followed up until December 2016 with a median duration follow-up of 8.5 (interquartile range, 4.7-13.8) years. Statistical analysis began in April 2017.

Main Outcomes and Measures  Patients were followed up from MS onset date to the date of sustained EDSS 3.0, 4.0, and 6.0. To handle interval-censored observations, a Weibull model was fit, and the change in the risk of EDSS 3.0, 4.0, and 6.0 over calendar years was estimated and hazard ratios (HRs) with corresponding CIs were calculated.

Results  Of 7331 patients, 5196 (70.9%) were women, and the mean (SD) age at diagnosis was 38.3 (11.7) years. Adjusting for sex, number of clinic visits, diagnostic delay, and onset age, a 3% decrease per calendar year of diagnosis for the risk of sustained EDSS 3.0 (HR, 0.97; 95% CI, 0.96-0.97), a 6% decrease for the risk of EDSS 4.0 (HR, 0.94; 95% CI, 0.93-0.95), and a 7% decrease for the risk of EDSS 6.0 (HR, 0.93; 95% CI, 0.91-0.94) among patients with relapsing-onset MS was found. The trends were not significant for patients with progressive-onset MS (EDSS 3.0: HR, 1.01; 95% CI, 0.98-1.03; EDSS 4.0: HR, 1.00; 95% CI, 0.98-1.02; EDSS 6.0: HR, 1.00; 95% CI, 0.98-1.02).

Conclusions and Relevance  Risk of reaching major disability milestones has significantly decreased over the last decade in patients with relapsing-onset MS in Sweden. Several factors could potentially be responsible for this observation. However, given that no change was seen in disability accrual of patients with progressive-onset MS and the absence of efficacious treatment option in this group, increased use of more efficacious disease-modifying treatments could be a possible driver of this change.