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November 2022; 9 (6) Research ArticleOpen Access

Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3

A Systematic Review and Meta-analysis

Dalia Rotstein, Jacqueline M. Solomon, Maria Pia Sormani, Xavier Montalban, Xiang Y. Ye, Dina Dababneh, Alexandra Muccilli, Georges Saab, Prakesh Shah
First published October 12, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200032
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Article Information

vol. 9 no. 6 e200032
DOI: 
https://doi.org/10.1212/NXI.0000000000200032
PubMed: 
36224046
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received March 22, 2022
  • Accepted in final form August 2, 2022
  • First Published October 12, 2022.
Copyright & Usage: 
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Dalia Rotstein, MD, MPH,
    2. Jacqueline M. Solomon, MD,
    3. Maria Pia Sormani, PhD,
    4. Xavier Montalban, MD, PhD,
    5. Xiang Y. Ye, MSc,
    6. Dina Dababneh, MD,
    7. Alexandra Muccilli, MD,
    8. Georges Saab, MD and
    9. Prakesh Shah, MD, MSc
  1. Dalia Rotstein, MD, MPH,
    2. Scientific Advisory Boards:

    1. (1) Biogen (2) Sanofi Aventis (3) EMD Serono (4) Alexion (5) Roche (6) Novartis

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Sanofi Aventis (2) Roche (3) Novartis (4) EMD Serono (5) Alexion (6) Biogen

    Editorial Boards:

    1. Frontiers in Neurology, Associate Editor, 2019-2022

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Sanofi Aventis (2) Roche (3) Alexion (4) Biogen (5) EMD Serono (6) Novartis

    Speakers' Bureaus:

    1. (1) Alexion (2) Biogen (3) EMD Serono (4) Novartis (5) Roche (6) Sanofi Aventis

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. I have received research support from Roche.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. University of Toronto Division of Neurology

    Research Support, Foundations and Societies:

    1. I have received research support from the MS Society of Canada and the Consortium for Multiple Sclerosis Centers (CMSC).

    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. Jacqueline M. Solomon, MD,
    3. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. I have received speaker or consultant fees from Alexion, Biogen, and EMD Serono.

    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. Maria Pia Sormani, PhD,
    4. Scientific Advisory Boards:

    1. Medday, Merck, Sanofi, Roche, Novartis, GeNeuro, Biogen, Celgene, Immunic

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Merck, Sanofi, Novartis, Biogen, Roche

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Merck, Biogen, Sanofi, Roche, Novartis, GeNeuro, Immunic, Celgene

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Biogen, Roche, Merck, Novartis

    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

  4. Xavier Montalban, MD, PhD,
    5. Scientific Advisory Boards:

    1. (1) Actelion, (2) Alexion, (3) Biogen, (4) Bristol-Myers Squibb/Celgene, (5) EMD Serono, (6) Genzyme, (7) Hoffmann-La Roche, (8) Immunic, (9) Janssen Pharmaceuticals, (10) Medday, (11) Merck, (12) Mylan, (13) Nervgen, (14) Novartis, (15) Sanofi-Genzyme, (16) Teva Pharmaceutical, (17) TG Therapeutics

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Travel to scientific meetings: (1) Actelion, (2) Alexion, (3) Biogen, (4) Bristol-Myers Squibb/Celgene, (5) EMD Serono, (6) Genzyme, (7) Hoffmann-La Roche, (8) Immunic, (9) Janssen Pharmaceuticals, (10) Medday, (11) Merck, (12) Mylan, (13) Nervgen, (14) Novartis, (15) Sanofi-Genzyme, (16) Teva Pharmaceutical, (17) TG Therapeutics, (18) Excemed, (19) MSIF and (20) NMSS.

    Editorial Boards:

    1. Member of editorial boards: (1) Multiple Sclerosis Journal, (2) Journal of Neurology, (3) The International MS Journal, (4) Revista de Neurologia, (5) Therapeutic Advances in Neurological Disorders

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Biogen, (2) Celgene, (3) Merck, (4) Novartis, (5) Roche, (6) Sanofi-Genzyme and (7) Teva Pharmaceutical.

    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. (1) Vice-president, Multiple Sclerosis Foundation of Barcelona (FEM) and (2) President, Fundació Cemcat

    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. Xiang Y. Ye, MSc,
    6. 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

  6. Dina Dababneh, MD,
    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. Alexandra Muccilli, MD,
    8. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Commercial entity - Biogen speaking engagement for MS nurses, cheque.

    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

  8. Georges Saab, MD and
    9. 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

  9. Prakesh Shah, MD, MSc
    10. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Acta Obstetricia Gynecologica Scandinavica- editorial advisory board member 2013 onwards.

    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

  1. From the Department of Medicine, (D.R., A.M., G.S.), University of Toronto, Ontario, Canada; St. Michael's Hospital (D.R., A.M., G.S.), Toronto, Ontario, Canada; Department of Medicine, (J.M.S.), McMaster University, Hamilton, Ontario, Canada; Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genova, Italy; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genova, Italy; Department of Neurology and Cemcat (X.M.), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona; Department of Pediatrics (X.Y.Y., P.S.), Mount Sinai Hospital, Toronto, Canada; Columbia University Irving Medical Center (D.D.), Department of Neurology, New York City; York Presbyterian Hospital (NYP) (D.D.), New York City; and Institute of Health (P.S.), Policy, Management and Evaluation, University of Toronto, Canada.
  1. Correspondence
    Dr. Rotstein dalia.rotstein{at}unityhealth.to
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