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February 07, 2023; 100 (6) Research Article

Risk of Multiple Sclerosis Among Users of Antitumor Necrosis Factor α in 4 Canadian Provinces

A Population-Based Study

Lingyi Li, J. Antonio Aviña-Zubieta, Charles N. Bernstein, Gilaad G. Kaplan, Helen Tremlett, Hui Xie, Juan-Nicolás Peña-Sánchez, Ruth Ann Marrie, Mahyar Etminan
First published October 28, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201472
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Article Information

vol. 100 no. 6 e558-e567
DOI: 
https://doi.org/10.1212/WNL.0000000000201472
PubMed: 
36307225
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received May 27, 2022
  • Accepted in final form September 9, 2022
  • First Published October 28, 2022.

Article Versions

Copyright & Usage: 
© 2022 American Academy of Neurology

Author Disclosures

    1. Lingyi Li, MSc,
    2. J. Antonio Aviña-Zubieta, MD, MSc, PhD*,
    3. Charles N. Bernstein, MD,
    4. Gilaad G. Kaplan, MD, MPH,
    5. Helen Tremlett, PhD,
    6. Hui Xie, PhD,
    7. Juan-Nicolás Peña-Sánchez, MD, PhD,
    8. Ruth Ann Marrie, MD, PhD and
    9. Mahyar Etminan, PharmD, MSc*
  1. Lingyi Li, MSc,
    2. 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. (1) Canadian Institutes of Health Research (CIHR grant number THC-135235 <br><br>and PJT-166183). 2019-2021<br><br><br><br>(2) Canadian Institutes of Health Research Fred Frederick Banting and Charles <br><br>Best Canada Graduate Scholarships Doctoral Awards. 2020-2023

    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

  2. J. Antonio Aviña-Zubieta, MD, MSc, PhD*,
    3. 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

  3. Charles N. Bernstein, MD,
    4. Scientific Advisory Boards:

    1. Abbvie Canada, Amgen Canada, Avir Pharmaceuticals, <br>Bristol Myers Squibb Canada, Janssen Canada, Pfizer <br>Canada, Takeda Canada, Roche Canada, Sandoz Canada

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Speakers bureau for Abbvie Canada, Janssen Canada, Takeda <br>Canada, Pfizer Canada

    Editorial Boards:

    1. Editorial Advisory board for Journal of Canadian <br>Association of Gastroenterology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Takeda and Mylan Pharmaceuticals

    Speakers' Bureaus:

    1. Speaker fees from Abbvie Canada, Takeda Canada, Janssen <br>Canada, Pfizer Canada

    Other Activities:

    1. Education grants from Abbvie Canada, Janssen Canada, <br>Pfizer Canada, Takeda Canada

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Abbvie Canada, Sandoz Canada and Pfizer Canada have given <br>unrestricted investigator initiated grants

    Research Support, Government Entities:

    1. Canadian Institutes of Health Research, Research Manitoba

    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. legal consultant to Mylan Pharmaceuticals and Takeda and <br>3M

  4. Gilaad G. Kaplan, MD, MPH,
    5. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Dr. Kaplan has received honoraria for speaking from AbbVie, <br>Janssen, Pfizer, Amgen, Sandoz, Pendophram, and Takeda.

    Editorial Boards:

    1. Associate Editor, Gastroenterology

    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. Kaplan has received research support from Ferring.

    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

  5. Helen Tremlett, PhD,
    6. Scientific Advisory Boards:

    1. All non-profit:<br><br>&#x0095; National US surveillance system for MS. 2013-2019. <br>Invited by the US National MS Society to form an <br>advisory <br>group to enable the development of a national <br>surveillance <br>system capable of tracking the incidence and prevalence <br>of <br>MS. Monthly teleconferences; one face-to-face meeting: <br>Atlanta, Georgia (March 2014)<br>Status: Bipartisan legislation introduced to Congress - <br>'Advancing Research for Neurological Diseases Act, H.R. <br>292.'to guide the Centers for Disease Control and <br>Prevention <br>in tracking the incidence and prevalence of neurological <br>diseases, including Multiple Sclerosis and Parkinson's <br>disease [13th-Jan-2015; http://burgess.house.gov/blog/?<br>postid=397459]

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Helen Tremlett has, in the last five years, received <br>research support from the Canada Research Chair Program, <br>the National Multiple Sclerosis Society, the Canadian <br>Institutes of Health Research, the Multiple Sclerosis <br>Society of Canada, the Multiple Sclerosis Scientific <br>Research Foundation and the EDMUS Foundation (&#x0091;Fondation <br>EDMUS contre la scl&#x00E9;rose en plaques&#x0092;). In addition, in the <br>last five years, has had travel expenses or registration <br>fees prepaid or reimbursed to present at CME conferences <br>from the Consortium of MS Centres (2018), National MS <br>Society (2016, 2018), ECTRIMS/ ACTRIMS (2015, 2016, 2017, <br>2018, 2019, 2020, 2021, 2022), American Academy of <br>Neurology (2015, 2016, 2019). Speaker honoraria are either <br>declined or donated to an MS charity or to an unrestricted <br>grant for use by HT&#x0092;s research group.<br>Research Support, Foundations and Societies: <br>Canada Foundation for Innovation (CFI); Canadian <br>Institutes <br>of Health Research [#363635 (co-PI); #190898 (PI); <br>#404791; <br>#387503; #388480 (all as PI); #MOP-82738 (PI) and MOP-<br>119393 (PI) and MOP-106607 (PI)]; <br>the US National Multiple Sclerosis Society (Operating <br>grants: 2012-15; 2014-17), the <br>Multiple Sclerosis Society of Canada (2015-19: EGID <br>#2624 <br>(PI); 2016-19: EGID #2680 (co-PI); ) the The Multiple <br>Sclerosis Scientific and Research Foundation (2015-21 <br>(PI)); Canada Research Chair in Neuroepidemiology and <br>Multiple Sclerosis

    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. Canada Foundation for Innovation (CFI); Canadian <br>Institutes <br>of Health Research [#363635 (co-PI); #190898 (PI); <br>#404791; <br>#387503; #388480 (all as PI); #MOP-82738 (PI) and MOP-<br>119393 (PI) and MOP-106607 (PI)]; <br>the US National Multiple Sclerosis Society (Operating <br>grants: 2012-15; 2014-17), the <br>Multiple Sclerosis Society of Canada (2015-19: EGID <br>#2624 <br>(PI); 2016-19: EGID #2680 (co-PI); ) the The Multiple <br>Sclerosis Scientific and Research Foundation (2015-21 <br>(PI)); Canada Research Chair in Neuroepidemiology and <br>Multiple Sclerosis

    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

  6. Hui Xie, PhD,
    7. 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

  7. Juan-Nicolás Peña-Sánchez, MD, PhD,
    8. 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. (1) University of Saskatchewan

    Research Support, Foundations and Societies:

    1. (1) Royal University Hospital Foundation (2) Saskatchewan <br>Health Research Foundation (3) Crohn's and Colitis Canada (4) <br>Canadian Institutes of Health<br>Research.

    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

  8. Ruth Ann Marrie, MD, PhD and
    9. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Multiple Sclerosis Journal, <br>Editorial Board<br>Multiple Sclerosis Journal-ETC, Co-Editor (ended Dec 2020)<br>Neurology, Editorial Board (2022)

    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. Roche Canada (no direct funding to me or my institution), <br>Biogen (no direct funding to me or my institution)

    Research Support, Government Entities:

    1. Received support as principal <br>investigator from the<br>Canadian Institutes of Health <br>Research (2010-2023), and Research <br>Manitoba (2014-2022) and as co-investigator from US <br>Department of Defense (2020-2023).

    Research Support, Academic Entities:

    1. Waugh Family Chair in Multiple Sclerosis

    Research Support, Foundations and Societies:

    1. Received support as principal investigator from <br>Multiple Sclerosis Society of Canada (2009-2025) and the<br>National Multiple Sclerosis Society (2013-2023), and as <br>co-principal investigator from Multiple Sclerosis <br>Scientific Foundation (2009-2021). <br>Received support from <br>Consortium of Multiple Sclerosis Centers (2004-2009, <br>2011-2014, 2016-2022), Crohn's and Colitis Canada (2014-<br>2023), The Arthritis Society (2021-2023)

    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

  9. Mahyar Etminan, PharmD, MSc*
    10. 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. (1) Consulted in Propecia and Sexual Dysfuncation litigation <br>and Abilify and gambling litgation, 2017; (2) Consulted in <br>the Mirena and intracranial hypertension litigation, 2016

  1. From the Experimental Medicine Program (L.L., J.A.A.-Z., M.E.), Division of Rheumatology (J.A.A.-Z.), Department of Medicine, Division of Neurology (H.T.), Faculty of Medicine, and Departments of Ophthalmology and Visual Sciences (M.E.), Medicine and Pharmacology, University of British Columbia, Vancouver; Arthritis Research Canada (L.L., J.A.A.-Z., H.X.), Vancouver, British Columbia; Departments of Internal Medicine (C.N.B., R.A.M.) and Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg; Departments of Medicine and Community Health Sciences (G.G.K.), University of Calgary, Alberta; The Djavad Mowafaghian Centre for Brain Health (H.T.), Vancouver, British Columbia; Faculty of Health Sciences (H.X.), Simon Fraser University, Burnaby, British Columbia; and Department of Community Health and Epidemiology (J.-N.P.-S.), College of Medicine, University of Saskatchewan, Saskatoon, Canada.
  1. Correspondence
    Dr. Etminan etminanm{at}mail.ubc.ca
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Article usage: October 2022 to February 2023

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