Early versus later treatment start in multiple sclerosis: a register-based cohort study

Eur J Neurol. 2018 Oct;25(10):1262-e110. doi: 10.1111/ene.13692. Epub 2018 Jul 9.


Background and purpose: To assess long-term treatment effectiveness of disease-modifying therapy (DMT) initiated early in disease course versus later treatment start.

Methods: We included all Danish patients with multiple sclerosis (MS) treated with DMT through two nationwide population-based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted.

Results: The median follow-up time of 3795 patients was 7.0 (range 0.6-19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2-20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early-treated patients [HR, 1.42; 95% confidence interval (CI), 1.18-1.70; P < 0.001]. When stratified by sex, the increased hazard among later-treated women persisted (HR, 1.53; 95% CI, 1.22-1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93-1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96-1.99; P = 0.08).

Conclusions: Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.

Keywords: cohort study; epidemiology; immunomodulating therapy; multiple sclerosis; sex difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Disability Evaluation
  • Disease Progression
  • Female
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Interferon-beta / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Registries
  • Time-to-Treatment
  • Treatment Outcome
  • Young Adult


  • Immunologic Factors
  • Glatiramer Acetate
  • Interferon-beta