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Research paper
Excess mortality among patients with multiple sclerosis in Denmark has dropped significantly over the past six decades: a population based study
  1. Nils Koch-Henriksen1,2,
  2. Bjarne Laursen3,
  3. Egon Stenager2,4,
  4. Melinda Magyari2,5
  1. 1 Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, Denmark
  2. 2 The Danish Multiple Sclerosis Registry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  3. 3 National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
  4. 4 Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark
  5. 5 Department of Neurology, Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Dr Nils Koch-Henriksen, The Danish Multiple Sclerosis Registry, Copenhagen University Hospital Rigshospitalet, Section 7801 Blegdamsvej 9, DK 2100 Copenhagen, Denmark; koch-henriksen{at}


Background Lifetime expectancy in multiple sclerosis (MS) is reduced. Few studies have had sufficient follow-up or sufficient number of patients to assess if survival has improved with time. However, a recent meta-analysis found no time-dependent change in MS excess mortality across studies over recent decades.

Objective To investigate whether short-term all-cause excess mortality in patients with MS in the total Danish population has changed over the last six decades.

Patients and methods We included all patients with MS recorded in the nationwide Danish MS Registry with definite or probable MS and onset from 1950 through 1999. The Danish Civil Registration System provided date of death for all deceased patients with follow-up in 2015, and Statistics Denmark supplied specific population mortality. We calculated excess number of death per 1000 person-years (EDR) and standardised mortality ratio (SMR).

Results We included 18 847 patients among whom 6102 had died as opposed to 2492 expected deaths. EDR was 10.63 (95% CI 10.19 to 11.09) and a SMR was 2.45 (95% CI 2.39 to 2.51). The 15-year EDR dropped gradually from 11.29 (95% CI 9.95 to 12.73) in the 1950–1959 onset cohort to 2.56 (95% CI 1.98 to 3.18) in the 1990–1999 onset cohort, and SMR dropped from 4.48 (95% CI 4.06 to 4.92) to 1.80 (95% CI 1.62 to 1.99).

Conclusion The decline in short-term excess mortality in MS started decades before disease-modifying treatment of MS became available, before use of MRI became widespread, and before the McDonald diagnostic criteria were introduced. A change in the MS cohorts with fewer malignant cases may be a significant contributor.

  • Multiple sclerosis
  • outcome
  • mortality
  • natural history

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  • Contributors NK-H designed the study, contributed to data acquisition, performed the analyses and drafted the manuscript. BL critically revised the manuscript and the statistical methods. ES contributed to data acquisition, critically revised the manuscript and interpreted the results. MM contributed to the concept and design, critically revised the manuscript and interpreted the results.

  • Funding We are grateful to the Danish Multiple Sclerosis Society, which has supported and financed the Danish MS Registry since 1966 without restrictions.

  • Competing interests None declared.

  • Ethics approval The Danish MS Registry is approved for medical research by the Danish Data Protection agency, journal 2008540482. Data extracted for the present study contained no personal identification. According to the Danish regulations, ethical committees need not be involved in observational register studies. For the processing of register data, patient consent is not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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