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July 7, 2017

Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012

Sarah Burkill, MSc, Scott Montgomery, PhD, MohammadHossein Hajiebrahimi, PhD, Jan Hillert, PhD, Tomas Olsson, PhD, and Shahram Bahmanyar, PhDAuthors Info & Affiliations
August 8, 2017 issue
89 (6) 555-562
https://doi.org/10.1212/WNL.0000000000004216
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Abstract

Objective:

To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden.

Methods:

Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS.

Results:

The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86–2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87–5.26) and infectious (HR 4.07, 95% CI 3.70–4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79–7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95–2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators.

Conclusions:

There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.

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Supplementary Material

File (appendix_e-1.docx)

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Information & Authors

Information

Published In

Neurology®
Volume 89 • Number 6 • August 8, 2017
Pages: 555-562
PubMed: 28687718

Copyright

© 2017 American Academy of Neurology.

Publication History

Received: February 13, 2017
Accepted: May 15, 2017
Published online: July 7, 2017
Published in print: August 8, 2017

Permissions

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Disclosure

S. Burkill reports no disclosures relevant to the manuscript. S. Montgomery has received funding for MS-related research from F. Hoffman-La Roche, Novartis International AG, and AstraZeneca, as well as honoraria for serving on an advisory board for IMS Health. M. Hajiebrahimi reports no disclosures relevant to the manuscript. J. Hillert has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme, and Novartis and speaker's fees from Biogen, Novartis, Merck-Serono, Bayer-Schering, Teva, and Sanofi-Genzyme. He has served as principal investigator for projects or received unrestricted research support from BiogenIdec, Merck-Serono, Teva, Sanofi-Genzyme, and Bayer-Schering. T. Olsson has received unrestricted MS research grants or speaker or advisory board honoraria from Biogen, Novartis, and Genzyme. S. Bahmanyar has received funding for MS-related research from F. Hoffman-La Roche, Novartis International AG, and AstraZeneca. Go to Neurology.org for full disclosures.

Study Funding

This study was funded by F. Hoffman La Roche and Novartis Pharma AG.

Authors

Affiliations & Disclosures

Sarah Burkill, MSc
From the Clinical Epidemiology Unit (S.B., S.M., M.H., S.B) and Centre for Pharmacoepidemiology (S.B., S.B.), Department of Medicine, Solna, Karolinska Institutet, Stockholm; Clinical Epidemiology and Biostatistics (S.M.), School of Medical Sciences, Örebro University, Sweden; Department of Epidemiology and Public Health (S.M.), University College London, UK; Division of Neurology (J.H.) and Neuroimmunology Unit (T.O.), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Biostatistics and Epidemiology Unit (M.H., S.B.), Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Scott Montgomery, PhD
From the Clinical Epidemiology Unit (S.B., S.M., M.H., S.B) and Centre for Pharmacoepidemiology (S.B., S.B.), Department of Medicine, Solna, Karolinska Institutet, Stockholm; Clinical Epidemiology and Biostatistics (S.M.), School of Medical Sciences, Örebro University, Sweden; Department of Epidemiology and Public Health (S.M.), University College London, UK; Division of Neurology (J.H.) and Neuroimmunology Unit (T.O.), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Biostatistics and Epidemiology Unit (M.H., S.B.), Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Longitudinal and Life Course Studies, section editor (health), 2014-
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
AstraZeneca 2013 F. Hoffman-La Roche Ltd 2013 Novartis Pharmaceuticals 2013. F. Hoffman-La Roche Ltd 2015
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
KID (Karolinska Institutet funding for doctoral students) 2015 (Co- investigator). The Progressive MS Alliance 2014 (Co-investigator) Folksam 2014 (Co-investigator)
Research Support, Foundations and Societies:
1.
Barncancerfonden 2015 (Co-investigator). Nyckelfonden 2015 (Principal investigator)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
MohammadHossein Hajiebrahimi, PhD
From the Clinical Epidemiology Unit (S.B., S.M., M.H., S.B) and Centre for Pharmacoepidemiology (S.B., S.B.), Department of Medicine, Solna, Karolinska Institutet, Stockholm; Clinical Epidemiology and Biostatistics (S.M.), School of Medical Sciences, Örebro University, Sweden; Department of Epidemiology and Public Health (S.M.), University College London, UK; Division of Neurology (J.H.) and Neuroimmunology Unit (T.O.), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Biostatistics and Epidemiology Unit (M.H., S.B.), Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Jan Hillert, PhD
From the Clinical Epidemiology Unit (S.B., S.M., M.H., S.B) and Centre for Pharmacoepidemiology (S.B., S.B.), Department of Medicine, Solna, Karolinska Institutet, Stockholm; Clinical Epidemiology and Biostatistics (S.M.), School of Medical Sciences, Örebro University, Sweden; Department of Epidemiology and Public Health (S.M.), University College London, UK; Division of Neurology (J.H.) and Neuroimmunology Unit (T.O.), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Biostatistics and Epidemiology Unit (M.H., S.B.), Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
Disclosure
Scientific Advisory Boards:
1.
Dr Hillert received honoraria for serving on advisory boards for BiogenIdec and Sanofi-Genzyme
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Received travel expenses and/or honoraria for lectures or educational activities for BiogenIdec, Merck-Serono, Bayer-Shering, Novartis, Sanofi-Genzyme and TEVA
Editorial Boards:
1.
J Neuroimmunology, no compensation
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Dr Hillert research on MS is currently supported by Biogen, Novartis and Sanofi-Genzyme. In the past Dr Hillert has also received unrestricted research grants from Merck-Serono and Bayer-Schering. and Bayer-Schering.
Research Support, Government Entities:
1.
Dr Hillert receives research support from the Swedish Research Council
Research Support, Academic Entities:
1.
Dr Hillert research on MS genetics is funded by the Karolinska Institute
Research Support, Foundations and Societies:
1.
Dr Hillert research on MS is supported by the Swedish Brain Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Tomas Olsson, PhD
From the Clinical Epidemiology Unit (S.B., S.M., M.H., S.B) and Centre for Pharmacoepidemiology (S.B., S.B.), Department of Medicine, Solna, Karolinska Institutet, Stockholm; Clinical Epidemiology and Biostatistics (S.M.), School of Medical Sciences, Örebro University, Sweden; Department of Epidemiology and Public Health (S.M.), University College London, UK; Division of Neurology (J.H.) and Neuroimmunology Unit (T.O.), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Biostatistics and Epidemiology Unit (M.H., S.B.), Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
Disclosure
Scientific Advisory Boards:
1.
Advisory boards BiogenIdec 2006- 2016 and Genzyme/SanofiAventis 2006- 2016, Merck 2016. Novartis 2009-2016. With all of them advice with regard to therapy in multiple sclerosis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
For lectures on Multiple sclerosis, Novartis 2008 and BiogenIdec 2006, 2007, 2008, 2009, 2010, 2011, 2012 and 2016. Genzyme 2012 and 2013.
Editorial Boards:
1.
Co-editor 2006 in Current opinion in Immunology
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
1)Merck, 2)BiogenIdec, 3)SanofiAventis, 4) Novartis
Research Support, Government Entities:
1.
Tomas Olsson (TO) has received grant support from The Swedish Research council (07488), EU fp7, Euratrans Neurinox 2012-2016 and combiMS, 2013-2014, Swedish Brain foundation,the AFA foundation, Knut and Alice Wallenberg foundation.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
The Knut and Allice Wallenberg foundation, The Swedish Brain foundation, the AFA foundation, EU FP 7 Neurinox . TO has also received unrestricted research grants from Bayer Schering, Genzyme/Sanofi-AventisBiogen Idec and AstraZeneca.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Shahram Bahmanyar, PhD
From the Clinical Epidemiology Unit (S.B., S.M., M.H., S.B) and Centre for Pharmacoepidemiology (S.B., S.B.), Department of Medicine, Solna, Karolinska Institutet, Stockholm; Clinical Epidemiology and Biostatistics (S.M.), School of Medical Sciences, Örebro University, Sweden; Department of Epidemiology and Public Health (S.M.), University College London, UK; Division of Neurology (J.H.) and Neuroimmunology Unit (T.O.), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Biostatistics and Epidemiology Unit (M.H., S.B.), Health Faculty, Golestan University of Medical Sciences, Golestan, Iran.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author

Notes

Correspondence to Sarah Burkill: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Sarah Burkill conducted the statistical analysis and provided initial interpretation of the results. This author also wrote the first draft of the manuscript with supervision from Scott Montgomery and Shahram Bahmanyar. Scott Montgomery was involved in the study concept and design and the acquisition of data. This author also provided supervision for this study and provided feedback and comments for earlier drafts that contributed to the final draft of the manuscript. MohammadHossein Hajiebrahimi provided feedback and comments that contributed to the final version of the manuscript. Jan Hillert was involved in the study concept and design and the acquisition of the data. This author also provided feedback from earlier drafts that contributed to the final manuscript. Tomas Olsson was involved in the study concept and design and the acquisition of the data. This author also provided feedback and comments that contributed to the final manuscript. Shahram Bahmanyar was involved in the study concept and design and the acquisition of data. This author also provided supervision for this study and provided feedback and comments for earlier drafts that contributed to the final draft of the manuscript.

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