Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective:

To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study.

Methods:

CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort).

Results:

DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance.

Conclusions:

The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS.

Classification of evidence:

This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.

Related collections

Most cited references 15

Record: found
Abstract: found
Article: not found

Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway.

Robert Scannevin, Sowmya Chollate, Hiral Patel … (2012)

Oxidative stress is central to the pathology of several neurodegenerative diseases, including multiple sclerosis, and therapeutics designed to enhance antioxidant potential could have clinical value. The objective of this study was to characterize the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) on cellular resistance to oxidative damage in primary cultures of central nervous system (CNS) cells and further explore the dependence and function of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in this process. Treatment of animals or primary cultures of CNS cells with DMF or MMF resulted in increased nuclear levels of active Nrf2, with subsequent up-regulation of canonical antioxidant target genes. DMF-dependent up-regulation of antioxidant genes in vivo was lost in mice lacking Nrf2 [Nrf2(-/-)]. DMF or MMF treatment increased cellular redox potential, glutathione, ATP levels, and mitochondrial membrane potential in a concentration-dependent manner. Treating astrocytes or neurons with DMF or MMF also significantly improved cell viability after toxic oxidative challenge in a concentration-dependent manner. This effect on viability was lost in cells that had eliminated or reduced Nrf2. These data suggest that DMF and MMF are cytoprotective for neurons and astrocytes against oxidative stress-induced cellular injury and loss, potentially via up-regulation of an Nrf2-dependent antioxidant response. These data also suggest DMF and MMF may function through improving mitochondrial function. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic containing DMF as the active ingredient.

0 comments Cited 167 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.

James Miller, Michael Sailer, P Brex … (2002)

In patients with isolated syndromes that are clinically suggestive of multiple sclerosis, such as optic neuritis or brain-stem or spinal cord syndromes, the presence of lesions as determined by T2-weighted magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis will develop. We sought to determine the relation between early lesion volume, changes in volume, and long-term disability. Seventy-one patients in a serial MRI study of patients with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured with the use of Kurtzke's Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability). Clinically definite multiple sclerosis developed in 44 of the 50 patients (88 percent) with abnormal results on MRI at presentation and in 4 of 21 patients (19 percent) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to multiple sclerosis). The EDSS score at 14 years correlated moderately with lesion volume on MRI at 5 years (r=0.60) and with the increase in lesion volume over the first 5 years (r=0.61). In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment.

0 comments Cited 127 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.

Ludwig Kappos, Ralf Gold, David H Miller … (2008)

Oral fumarate (BG00012) might have dual anti-inflammatory and neuroprotective effects. Our aim was to assess the efficacy and safety of BG00012 in patients with relapsing-remitting multiple sclerosis. 257 patients, aged 18-55 years, with relapsing-remitting multiple sclerosis were randomly assigned to receive 120 mg once daily (n=64), 120 mg three times daily (n=64), or 240 mg three times daily (n=64) BG00012, or placebo (n=65) for 24 weeks. During an extension period of 24 weeks for safety assessment, patients treated with placebo received BG00012 240 mg three times daily. The primary endpoint was total number of new gadolinium enhancing (GdE) lesions on brain MRI scans at weeks 12, 16, 20, and 24. Additional endpoints included cumulative number of new GdE lesions (weeks 4-24), new or enlarging T2-hyperintense lesions, new T1-hypointense lesions at week 24, and annualised relapse rate. Analysis was done on the efficacy-evaluable population. Safety and tolerability were also assessed. This study is registered with ClinicalTrials.gov, number NCT00168701. Treatment with BG00012 240 mg three times daily reduced by 69% the mean total number of new GdE lesions from week 12 to 24 compared with placebo (1.4 vs 4.5, p<0.0001). It also reduced number of new or enlarging T2-hyperintense (p=0.0006) and new T1-hypointense (p=0.014) lesions compared with placebo. BG00012 reduced annualised relapse rate by 32% (0.44 vs 0.65 for placebo; p=0.272). Adverse events more common in patients given BG00012 than in those given placebo included abdominal pain, flushing, and hot flush. Dose-related adverse events in patients on BG00012 were headache, fatigue, and feeling hot. The anti-inflammatory effects and favourable safety profile of BG00012 warrant further long-term phase III studies in large patient groups.

0 comments Cited 122 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

David H. Miller:

Comment :

Scientific Advisory Boards:

1. Novartis, 2. GlaxoSmithKline, 3. Bayer Schering, 4. Biogen Idec 5. US National Institutes of Health 6. Merck 7. Chugai 8. Mitsubishi Pharma Europe

Gifts:

NONE

Funding for travel or speaker honoraria:

1. Biogen Idec, 2. Novartis, 3. Bayer Schering 4. GlaxoSmithKline 5. National MS Society, Cleveland Clinic 6. Merck 7. Chugai 8. Mitsubishi Pharma Europe

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

McAlpines Multiple Sclerosis fourth edition

Employment, Commercial Entity:

Current employment:Professor of Clinical Neurology, UCL UCL Institute of Neurology, London

Consultancies:

1. GlaxoSmithKline, 2. Biogen Idec 3. Novartis 4. Merck 5. Chugai 6. Mitsubishi Pharma Europe 7. Bayer Schering Pharma

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

1. Research grants to my employer UCL Institute of Neurology for MRI analysis of MS trials from Biogen Idec, GlaxoSmithKline, Novartis and Merck

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

1. MS Society of Great Britain & Northern Ireland 2. UK National Institute for Health Research 4. MS Research Australia

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Robert J. Fox:

Comment :

Scientific Advisory Boards:

Biogen Idec, Novartis

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

Editorial Board, Neurology Editorial Board, Multiple Sclerosis Journal

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

Biogen Idec, GlaxoSmithKline, MedDay, Novartis, Questcor, Teva, and XenoPort

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

Research grant from Novartis.

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

National MS Society, RC 1004-A-5, 2010- 2013; RG 4778-A-6, 2013-2018; NIH 1U01NS082329-01A1, 2013- 2018

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

J. Theodore Phillips:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for travel or speaker honoraria:

1. Acorda 2. Biogen-Idec 3. Genzyme 4. Sanofi

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

NONE

Speakers' Bureaus:

1. Acorda 2. Biogen-Idec 3. Genzyme 4. Sanofi

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

1. Biogen Idec 2. Roche

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Michael Hutchinson:

Comment :

Scientific Advisory Boards:

Commercial: Since 2007 I serve on the medical advisory board of the BG00012 study of fumerates in RRMS sponsored by Biogen Idec. Non- Commercial Funded Research: Health Research Board (Ireland) Clinical scientist Award 2012-5: Foundation for Dystonia Research.

Gifts:

NONE

Funding for travel or speaker honoraria:

received honoraria for speaking engagements on behalf of Biogen Idec, Bayer Schering and Novartis 2007-2014.

Editorial Boards:

I serve on the editorial board of the Multiple Sclerosis Journal

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

NONE

Speakers' Bureaus:

Biogen Idec, 2005-present

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

NONE

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

Grant from Dystonia Ireland, 2007-2009.

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Eva Havrdova:

Comment :

Scientific Advisory Boards:

1. Biogen Idec 2. Novartis 3. Teva 4. Genzyme

Gifts:

NONE

Funding for travel or speaker honoraria:

1. Biogen Idec 2. Novartis 3. Teva 4. Genzyme 5. Alkermes 6. Roche

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

1. Biogen Idec 2. Novartis 3. Teva 4. Genzyme 5. Alkermes 6. Roche

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

(1) Biogen Idec, grant support for gait study

Research Support, Government Entities:

1. European Commission Grant: ABIRISK - IMI (2012-2016), investigator 2. Czech Ministry of Education: PRVOUK-P26/LF1/4 (2013-2016), investigator

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Mariko Kita:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for travel or speaker honoraria:

commercial entity (BiogenIdec, Genzyme, Novartis), travel reimbursement

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

Virginia Mason Medical Center has received honoraria payments for my participation as a consultant. Commercial (BiogenIdec, Novartis)

Speakers' Bureaus:

Virginia Mason Medical Center has received honoraria payments for my participation as a speaker. Commercial (BiogenIdec, Genzyme)

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

1)BiogenIdec 2)Novartis 3)Genentech 4)Serono 5? Accorda

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Claudia A.M. Wheeler-Kingshott:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

Functional Neurology, co-editor, 2012 - ongoing

Patents:

NONE

Publishing Royalties:

Quantitative MRI of the Spinal Cord, Elsevier, March 2014

Employment, Commercial Entity:

NONE

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

NONE

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Daniel J. Tozer:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

(1) Part of my salary for performing this work was paid by Biogen Idec in the form of payment to UCL for performing clinical trials (1) Part of my salary was paid by Novartis in the form of payment to UCL for performing clinical trials

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

David G. MacManus:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

Biogen Idec, Novartis

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Tarek A. Yousry:

Comment :

Scientific Advisory Boards:

Biogen Idec Novartis

Gifts:

NONE

Funding for travel or speaker honoraria:

1. Biogen, Travel and speaker honoraria 2. ESOR, Travel and speaker honoraria

Editorial Boards:

1. The Egyptian Journal of Radiology and Nuclear Medicine , Associate Editor, 2012-2013 2. Neuroradiology, Board member, 2012-2013

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

NONE

Consultancies:

1. Biogen Idec

Speakers' Bureaus:

1. ESOR

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

1. GlaxoSmithKline 2. Novartis 3. Biogen Idec

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

Medical Research Council

Research Support, Foundations and Societies:

1. NIHR Comprehensive Biomedical Research Centre 2. MS Society of Great Britain and Northern Ireland 4. Stroke Association 5. British Heart Foundation 6. Wellcome Trust 7. MRC

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Mary Goodsell:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

Circle Science, Scientific Director, 3 years

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

NONE

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Minhua Yang:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

BiogenIdec, Principal Biostatistician, 13 years. Stock/Stock Options, Medical Equipment & Materials: BiogenIdec, 10 years.

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

NONE

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Ray Zhang:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

Employee of Biogen Idec.

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

NONE

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Vissia Viglietta:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

I am a Biogenidec employee

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

NONE

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Katherine T. Dawson:

Comment :

Scientific Advisory Boards:

NONE

Gifts:

NONE

Funding for Travel or Speaker Honoraria:

NONE

Editorial Boards:

NONE

Patents:

NONE

Publishing Royalties:

NONE

Employment, Commercial Entity:

Biogen Idec, Vice President Global Medical Neurology, 2004 - present

Consultancies:

NONE

Speakers' Bureaus:

NONE

Other Activities:

NONE

Clinical Procedures or Imaging Studies:

NONE

Research Support, Commercial Entities:

I am employed by Biogen Idec, Vice President, Global Medical Neurology, 2004- present) Stock/Stock Options, Medical Equipment & Materials: I hold stock in Biogen Idec.

Research Support, Government Entities:

NONE

Research Support, Academic Entities:

NONE

Research Support, Foundations and Societies:

NONE

Stock/Stock Options/Board of Directors Compensation:

NONE

License Fee Payments, Technology or Inventions:

NONE

Royalty Payments, Technology or Inventions:

NONE

Stock/Stock Options, Research Sponsor:

NONE

Stock/Stock Options, Medical Equipment & Materials:

NONE

Legal Proceedings:

NONE

Journal

Journal ID (nlm-ta): Neurology

Journal ID (iso-abbrev): Neurology

Journal ID (hwp): neurology

Journal ID (publisher-id): neur

Journal ID (pmc): neurology

Journal ID (publisher-id): NEUROLOGY

Title: Neurology

Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )

ISSN (Print): 0028-3878

ISSN (Electronic): 1526-632X

Publication date (Print): 17 March 2015

Publication date PMC-release: 17 March 2015

Volume: 84

Issue: 11

Pages: 1145-1152

Affiliations

From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

Author notes

Correspondence to Dr. Miller: david.h.miller@ 123456ucl.ac.uk

Coinvestigators are listed on the Neurology® Web site at Neurology.org.

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. The Article Processing Charge was paid by Biogen Idec.

Article

Publisher ID: NEUROLOGY2013532259

DOI: 10.1212/WNL.0000000000001360

PMC ID: 4371413

PubMed ID: 25681448

SO-VID: 0e1202dc-e787-4d6e-b951-cf325c09e14e

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

History

Date received : 14 June 2013

Date accepted : 21 November 2014

Custom metadata

OPEN-ACCESS TRUE

special-property triangle

Data availability:

Comments

Comment on this article

scite_

Cited by 36

See all cited by

Most referenced authors 358

See all reference authors

- Version 1
- Version 1

Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study

Read this article at

Abstract

Objective:

Methods:

Results:

Conclusions:

Classification of evidence:

Related collections

Karger: Neurology and Neuroscience

Most cited references 15

Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway.

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.

Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 252

Cited by 36

Most referenced authors 358