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April 23, 2018

Comment on 2018 American Academy of Neurology guidelines on disease-modifying therapies in MS

June 12, 2018 issue
90 (24) 1106-1112

Abstract

The American Academy of Neurology has published a comprehensive review and guidelines for the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) for the first time since 2002. These guidelines represent the work of MS experts, patients, and guideline experts and are based on their review of randomized controlled trials and observational evidence that addresses a set of prespecified questions related to starting, switching, and potentially discontinuing DMTs. Many of the recommendations address decision-making regarding the use of DMTs and incorporate the perspective of patients. Modified Delphi methods were used to establish consensus recommendations that were assigned a level of clinical obligation (actions a clinician must [A], should [B], or may [C] do). Most guideline recommendations are level B. Few reached level A, and several achieved only level C, primarily because of lack of evidence. The guidelines eschew formal treatment algorithms and do not address financial considerations and a variety of other controversies. We identify remaining uncertainties, the most important of which is the choice of available DMTs for the average newly diagnosed patient. We reiterate a number of research needs identified in the guidelines that could affect the use of DMTs, including improved definition of breakthrough disease requiring change in therapy, development of better and universally accepted definitions of both benign and aggressive MS, more and longer-duration comparative effectiveness trials, discovery and validation of biomarkers of disease activity and response to therapy, and development of treatment strategies focused on neuroprotection, remyelination, and neural repair.

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Information & Authors

Information

Published In

Neurology®
Volume 90Number 24June 12, 2018
Pages: 1106-1112
PubMed: 29685920

Publication History

Received: January 19, 2018
Accepted: March 27, 2018
Published online: April 23, 2018
Published in print: June 12, 2018

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Disclosure

J.R. Corboy: research funding from the National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, MedDay, Novartis, Biogen; receives compensation as editor of Neurology: Clinical Practice; has received speaking honorarium from PRIME CME and the Rocky Mountain MS Center. B.G. Weinshenker: royalties from RSR Ltd., Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders; member of an adjudication committee for clinical trials in NMO being conducted by MedImmune and Alexion pharmaceutical companies; consultant for Caladrius Biosciences and Brainstorm Therapeutics regarding potential clinical trials for NMO; member of data safety monitoring committee for clinical trials in multiple sclerosis conducted by Novartis. D.M. Wingerchuk: personal compensation as a consultant for Caladrius Biosciences, Inc., Brainstorm Cell Therapeutics, and Celgene; as a member of the adjudication committee of a clinical trial for MedImmune; and as co–editor-in-chief of The Neurologist; research/grant support for clinical trials from Alexion Pharmaceuticals, Inc., and Terumo BCT, Inc. Go to Neurology.org/N for full disclosures.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

John R. Corboy, MD
From the University of Colorado (J.R.C.), School of Medicine, Aurora, CO; Mayo Clinic (B.G.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Prime CME, Honorarium
Editorial Boards:
1.
Editor, Neurology: Clinical Practice
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.
Novartis Med Day Biogen
Research Support, Government Entities:
1.
PCORI, PI, 2017-2020 NMSS, PI 2017-ongoing
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) National MS Society
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.
Has reviewed case files, offered opinions, and provided expert testimony in medico-legal cases.
Brian G. Weinshenker, MD
From the University of Colorado (J.R.C.), School of Medicine, Aurora, CO; Mayo Clinic (B.G.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
Disclosure
Scientific Advisory Boards:
1.
(1) Novartis data safety monitoring board member
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
1. Canadian Journal of Neurological Sciences, editorial board member, 2006-present; no compensation 2. Turkish Journal of Neurology, editorial board member, 2005-present; no compensation 3. Neurology, editorial board member, 2014-present; no compensation
Patents:
1.
1) NMO-IgG for diagnosis of neuromyelitis optica; application 20050112116; patent issued and technology licensed to R.S.R. Ltd.,Oxford University,MVZ Labor PD Dr. Volkmann und Kollegen GbR, Hospices Civil de Lyon
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1. Caladrius: consulting regarding design of neuromyelitis optica clinical trial 2. Brainstorm Therapeutics: consulting regarding design of neuromyelitis optica clinical trial
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
(1)MedImmune Pharmaceuticals, Adjudication Committee Member (2)Alexion Pharmaceuticals, Adjudication Committee Member
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.
Guthy Jackson Charitable Foundation, sponsor of research in NMO, 10/2008-08/2017
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NMO-IgG for diagnosis of neuromyelitis optica; patent issued and technology licensed to R.S.R. Ltd., Oxford University, MVZ Labor PD Dr. Volkmann und Kollegen GbR and Hospices Civil de Lyon
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Dean M. Wingerchuk, MD
From the University of Colorado (J.R.C.), School of Medicine, Aurora, CO; Mayo Clinic (B.G.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1) The Neurologist, Co-Editor-in-Chief, 2014-present.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) MedImmune, (2) Caladrius, (3) ONO Pharmaceuticals; (4) Celgene; (5) Brainstorm Therapeutics.
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Alexion,(2) TerumoBCT
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

Notes

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

Author Contributions

Study concept and design: Drs. Corboy, Weinshenker, and Wingerchuk. Acquisition of data: Drs. Corboy, Weinshenker, and Wingerchuk. Analysis and interpretation: Drs. Corboy, Weinshenker, and Wingerchuk. Critical revision of the manuscript: Drs. Corboy, Weinshenker, and Wingerchuk. Study supervision: Drs. Corboy, Weinshenker, and Wingerchuk.

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