Absinta M, Lassmann H, Trapp BD. Mechanisms underlying progression in multiple sclerosis. Curr Opin Neurol. 2020;33:277-285.
Absinta M, Sati P, Masuzzo F, et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. 2019;76:1474-1483.
Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609.
Antel J, Antel S, Caramanos Z, et al. Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol. 2012;123:627-638.
Baecher-Allan C, Kaskow BJ, Weiner HL. Multiple sclerosis: mechanisms and immunotherapy. Neuron. 2018;97:742-768.
Bar-Or A. The immunology of multiple sclerosis. Semin Neurol. 2008;28:29-45.
Benjamins JA, Nedelkoska L, Touil H, et al. Exosome-enriched fractions from MS B cells induce oligodendrocyte death. Neurol Neuroimmunol Neuroinflamm. 2019;6:e550.
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15:545-558.
Dutta R, Trapp BD. Relapsing and progressive forms of multiple sclerosis--insights from pathology. Curr Opin Neuro. 2014;27:271-278.
Elliott C, Arnold DL, Chen H, et al. Patterning chronic active demyelination in slowly expanding/evolving white matter MS lesions. AJNR Am J Neuroradiol. 2020;41:1584-1591.
Elliott C, Belachew S, Wolinsky JS, et al. Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis. Brain. 2019;142-2787-2799.
Elliott C, Wolinsky JS, Hauser SL, et al. Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions. Mult Scler. 2019;25:1915-1925.
Filippi M, Bar-Or A, Piehl F, et al. Multiple sclerosis. Nat Rev Dis Primers. 2018;4:43.
Freedman MS, Bar-Or A, Oger J, et al. A phase III study evaluating the efficacy and safety of MPB8298 in secondary progressive MS. Neurology. 2011;77:1551-1560.
Freedman MS, Devonshire V, Duquette P, et al. Treatment optimization in multiple sclerosis: Canadian MS Working Group recommendations. Can J Neurol Sci. 2020;47:437-455.
Freedman MS, Patry DG, Grand'Maison F, et al. Treatment optimization in multiple sclerosis. Can J Neurol Sci. 2004;31:157-168.
Freedman MS, Selchen D, Arnold DL, et al. Treatment optimization in MS: Canadian MS Working Group Updated Recommendations. Can J Neurol Sci. 2013;40:307-323.
Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol. 2015;78:710-721.
Gillen KM, Mubarak M, Nguyen TD, et al. Significance and in vivo detection of iron-laden microglia in white matter multiple sclerosis lesions. Front Immunol. 2018;9:255.
Hauser SL, Bar-Or JA, Cohen JA, et al. Ofatumumab versus teriflunomide in multiple sclerosis. N Engl J Med. 2020;383:546-557.
Hawker K, O'Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized, double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66:460-471.
Hendriks RW. Drug discovery: new BTK inhibitor holds promise. Nat Chem Biol. 2011;7:4-5.
Howell OW, Reeves CA, Nicholas R, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain. 2011;134:2755-2771.
Kalb R, Beier M, Benedict RH., et al. Recommendations for cognitive screening and management in multiple sclerosis care. Mult Scler. 2018;24:1665-1680.
Kapoor R, Ho PR, Campbell N, et al. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018;17:405-415.
Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391:1263-1273.
Kappos L, Montalban X, Cohen JA, et al. Effect of ofatumumab treatment on disability progression independent of relapse activity in patients with relapsing multiple sclerosis. Presented at: 6th Congress of the European Academy of Neurology; May 23-26, 2020; Paris, France. Presentation O2034.
Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1-9.
Lassmann H. Pathogenic mechanisms associated with different clinical courses of multiple sclerosis. Front Immunol. 2018;9:3116.
Li R, Patterson KR, Bar-Or A. Reassessing B cell contributions in multiple sclerosis. Nat Immunol. 2018;19:696-707.
Lisak RP, Nedelkoska L, Benjamins JA, et al. B cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro. J Neuroimmunol. 2017;308:88-99.
Lublin F, Miller DH, Freedman MS, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387:1075-1084.
Magliozzi R, Howell OW, Reeves C, et al. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010;68:477-493.
Manouchehrinia A, Beiki O, Hillert J. Clinical course of multiple sclerosis: a nationwide cohort study. Mult Scler. 2017;23:1488-1495.
Mehta V, Pei W, Yang G, et al. Iron is a sensitive biomarker for inflammation in multiple sclerosis lesions. PLoS One. 2013;8:e57573.
Michael L, Touil H, Pikor NB, et al. B cells in the multiple sclerosis central nervous system: trafficking and contribution to CNS-compartmentalized inflammation. Front Immunol. 2015;6:636.
Montalban X, Arnold DL, Weber MS, et al. Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis. N Engl J Med. 2019;280:2406-2417.
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220.
Penner IK. Cognition in multiple sclerosis. Neurodegener Dis Manag. 2017;7:19-21.
Ramesh A, Schubert RD, Greenfield AL, et al. A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis. Proc Natl Acad Sci U S A. 2020;117:22932-22943.
Reali C, Magliozzi R, Roncaroli F, et al. B cell rich meningeal inflammation associates with increased spinal cord pathology in multiple sclerosis. Brain Pathol. 2020;30:779-793.
Rice CM, Cottrell D, Wilkins A, et al. Primary progressive multiple sclerosis: progress and challenges. J Neurol Neurosurg Psychiatry. 2013;84:1100-1106.
Suthiphosuwan S, Sati P, Absinta M, et al. Paramagnetic rim sign in radiologically isolated syndrome. JAMA Neurol. 2020;77:653-655.
Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162-173.
Tilling K, Lawton M, Robertson N, et al. Modelling disease progression in relapsing-remitting onset multiple sclerosis using multilevel models applied to longitudinal data from two natural history cohorts and one treated cohort. Health Technol Assess. 2016;20:1-48.
Torke S, Weber MS. Inhibition of Bruton's tyrosine kinase as a novel therapeutic approach in multiple sclerosis. Expert Opin Investig Drugs. 2020;29:1143-1150.
Touil H, Kobert A, Lebeurrier N, et al. Human central nervous system astrocytes support survival and activation of B cells: implications for MS pathogenesis. J Neuroinflammation. 2018;15:114.
Wang Q, Pechersky Y, Sagawa S, et al. Structural mechanism for Bruton's tyrosine kinase activation at the cell membrane. Proc Natl Acad Sci U S A. 2019;116:9390-9399.
Wolinsky JS, Narayana PA, O'Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007;61:14-24.
Zajicek J, Ball S, Wright D, et al. Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomized, placebo-controlled trial. Lancet Neurol. 2013;12:857-865.
Zuroff LR, Benjamins JA, Bar-Or A, et al. Inflammatory mechanisms underlying cortical injury in progressive multiple sclerosis. Neuroimmunol Neuroinflammation. 2020. doi:10.20517/2347-8659.2020.35. [Epub ahead of print]

WebMD Global requires each individual who is in a position to control the content of one of its educational activities to disclose any relevant financial relationships occurring within the past 12 months that could create a conflict of interest.

Steering Committee and Faculty

Jiwon Oh, MD, PhD, FRCPC

Assistant Professor
Division of Neurology
St. Michael's Hospital
University of Toronto
Toronto, Ontario, Canada

Disclosures

Disclosure: Jiwon Oh, MD, PhD, FRCPC, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Alexion; Biogen Idec; Bristol Myers Squibb; EMD Serono; Novartis; Roche; Sanofi-Genzyme
Received grants for clinical research from: Biogen Idec; EMD Serono; Roche

Amit Bar-Or, MD, FRCPC

Professor
Department of Neurology
University of Pennsylvania
Philadelphia, Pennsylvania, United States

Disclosures

Disclosure: Amit Bar-Or, MD, FRCPC, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Atara Biotherapeutics; Biogen Idec; Bristol Myers Squibb; Janssen/Actelion; Medimmune; Merck/EMD Serono; Novartis; Roche/Genentech; Sanofi-Genzyme
Received grants for clinical research from: Biogen Idec; Merck/EMD Serono; Novartis; Roche-Genentech

Virginia Devonshire, MD, FRCPC

Clinical Associate Professor
Division of Neurology
University of British Columbia
UBC Hospital
Vancouver, British Columbia, Canada

Disclosures

Disclosure: Virginia Devonshire, MD, FRCPC, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Alexion; Biogen; Novartis; Roche; Sanofi Genzyme; Serono; Teva Neurosciences
Served as a speaker or a member of a speakers bureau for: Alexion; Biogen; Novartis; Roche; Sanofi Genzyme; Serono; Teva Neurosciences

Editors

Leanne Fairley, BJ Hon

Medical Education Director, WebMD Global, LLC

Disclosures

Disclosure: Leanne Fairley, BJ Hon, has disclosed no relevant financial relationships.

Christin Melton, ELS

Scientific Content Manager, Medscape, LLC

Disclosures

Disclosure: Christin Melton, ELS, has disclosed no relevant financial relationships.

Content Reviewer

Amy Bernard, MS, BSN, RN-BC, CHCP

Director, Accreditation and Compliance, Medscape, LLC

Disclosures

Disclosure: Amy Bernard, MS, BSN, RN-BC, CHCP, has disclosed no relevant financial relationships.

CPD

Advances in the Management of MS: A Reappraisal of Disease Progression and Treatment Strategies

Authors: Jiwon Oh, MD, PhD, FRCPC; Amit Bar-Or, MD, FRCPC; Virginia Devonshire, MD, FRCPC
CPD Released: 12/14/2020
THIS ACTIVITY HAS EXPIRED
Valid for credit through: 12/14/2021

Start Activity

Target Audience and Goal Statement

This educational activity is intended for an international audience of non-US neurologists and nurses practicing in Canada.

The goal of this activity is to improve clinician knowledge regarding recent advances in managing multiple sclerosis (MS), new evidence about the pathophysiology of MS progression, the rationale and emerging data concerning B-cell-targeted therapies, and updated guidelines for managing MS.

Upon completion of this activity, participants will be able to:

Describe evidence supporting the progressive nature of MS
Discuss key clinical outcomes with B cell-targeting therapies in MS
Analyze evidence supporting the use of intensive treatment early in the disease course
Apply guideline recommendations that can be used to inform the treatment decision making process

Disclosures

Steering Committee and Faculty

Jiwon Oh, MD, PhD, FRCPC

Assistant Professor
Division of Neurology
St. Michael's Hospital
University of Toronto
Toronto, Ontario, Canada

Disclosures

Disclosure: Jiwon Oh, MD, PhD, FRCPC, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Alexion; Biogen Idec; Bristol Myers Squibb; EMD Serono; Novartis; Roche; Sanofi-Genzyme
Received grants for clinical research from: Biogen Idec; EMD Serono; Roche

Amit Bar-Or, MD, FRCPC

Professor
Department of Neurology
University of Pennsylvania
Philadelphia, Pennsylvania, United States

Disclosures

Disclosure: Amit Bar-Or, MD, FRCPC, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Atara Biotherapeutics; Biogen Idec; Bristol Myers Squibb; Janssen/Actelion; Medimmune; Merck/EMD Serono; Novartis; Roche/Genentech; Sanofi-Genzyme
Received grants for clinical research from: Biogen Idec; Merck/EMD Serono; Novartis; Roche-Genentech

Virginia Devonshire, MD, FRCPC

Clinical Associate Professor
Division of Neurology
University of British Columbia
UBC Hospital
Vancouver, British Columbia, Canada

Disclosures

Disclosure: Virginia Devonshire, MD, FRCPC, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Alexion; Biogen; Novartis; Roche; Sanofi Genzyme; Serono; Teva Neurosciences
Served as a speaker or a member of a speakers bureau for: Alexion; Biogen; Novartis; Roche; Sanofi Genzyme; Serono; Teva Neurosciences

Editors

Leanne Fairley, BJ Hon

Medical Education Director, WebMD Global, LLC

Disclosures

Disclosure: Leanne Fairley, BJ Hon, has disclosed no relevant financial relationships.

Christin Melton, ELS

Scientific Content Manager, Medscape, LLC

Disclosures

Disclosure: Christin Melton, ELS, has disclosed no relevant financial relationships.

Content Reviewer

Amy Bernard, MS, BSN, RN-BC, CHCP

Director, Accreditation and Compliance, Medscape, LLC

Disclosures

Disclosure: Amy Bernard, MS, BSN, RN-BC, CHCP, has disclosed no relevant financial relationships.

Accreditation Statements

This program was co-developed by the Canadian Neurological Sciences Federation and WebMD Global, with the support of Hoffmann-La Roche Limited and was planned to achieve scientific integrity, objectivity and balance.

For Physicians

This program is an Accredited Group Learning Activity (Section 1) as defined by the Maintenance of Certification program of the Royal College of Physicians and Surgeons of Canada, and approved by the Canadian Neurological Sciences Federation for 1.25 credits. This webinar was co-developed by the Canadian Neurological Sciences Federation and WebMD Global and was planned to achieve scientific integrity, objectivity and balance. The Webinar was supported by Hoffmann-La Roche Limited who provided an unrestricted educational grant.
Contact WebMD Global

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information about your eligibility to claim credit, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent participating in the activity. To successfully earn credit, participants must complete the activity online during the credit eligibility period that is noted on the title page.

Follow these steps to claim a credit certificate for completing this activity:

Read the information provided on the title page regarding the target audience, learning objectives, and author disclosures, read and study the activity content and then complete the post-test questions. If you earn a passing score on the post-test and we have determined based on your registration profile that you may be eligible to claim CPD credit for completing this activity, we will issue you a CPD credit certificate.
Once your CPD credit certificate has been issued, you may view and print the certificate from your CME/CE Tracker. CPD credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of the Medscape Education homepage.

We encourage you to complete an Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

From Medscape Education

CPD

Advances in the Management of MS: A Reappraisal of Disease Progression and Treatment Strategies

Authors: Jiwon Oh, MD, PhD, FRCPC; Amit Bar-Or, MD, FRCPC; Virginia Devonshire, MD, FRCPCFaculty and Disclosures

THIS ACTIVITY HAS EXPIRED

CPD Released: 12/14/2020

Valid for credit through: 12/14/2021

processing....

3T = 3 Tesla
7T = 7 Tesla
ADL = activity of daily living
APC = antigen-presenting cell
ARR = annualized relapse rate
BBB = blood-brain barrier
BCR = B-cell receptor
B_eff = effector B cell
B_reg = regulatory B cell
BTK = Bruton tyrosine kinase
CD4 = cluster of differentiation 4
CD8 = cluster of differentiation 8
CDP = confirmed disability progression
CIS = clinically isolated syndrome
CNS = central nervous system
COVID-19 = coronavirus disease 2019
CSF = cerebral spinal fluid
DMF = dimethyl fumarate
DMT = disease-modifying therapy
EAN = European Academy of Neurology
EDSS = Expanded Disability Status Scale
F = follicle
Gd = gadolinium
GM = gray matter
GM-CSF = granulocyte-macrophage colony stimulating factor
GML = gray matter lesion
IFN-γ = interferon gamma
Ig = immunoglobulin
IL = interleukin
iT_reg = induced regulatory T cell
IV = intravenous
LT = lymphotoxin
MAIT = mucosal-associated invariant T
MEDA = minimal evidence of disease activity
MRI = magnetic resonance imaging
MS = multiple sclerosis
NA = not applicable
NAGM = normal-appearing gray matter
NEDA = no evidence of disease activity
NS = not significant
nT_reg = natural regulatory T cell
OCB = oligoclonal band
OCR = ocrelizumab
OL = oligodendrocyte
PC = plasma cell
PDDS = Patient-Determined Disease Steps
PIRA = progression independent of relapse activity
PML = progressive multifocal leukoencephalopathy
PPMS = primary progressive multiple sclerosis
PRL = paramagnetic rim lesion
PRO = patient-reported outcome
QoL = quality of life
RCT = randomized controlled trial
RIS = radiologically isolated syndrome
RMS = relapsing multiple sclerosis
RRMS = relapsing-remitting multiple sclerosis
RRR = relative risk reduction
SDMT = Symbol Digit Modalities Test
SEL = slowly evolving/expanding lesion
SPMS = secondary progressive multiple sclerosis
Syk = spleen tyrosine kinase
Teff = effector T cell
TNFα = tumor necrosis factor alpha
TOR = treatment optimization recommendations
T_reg = regulatory T cell

« Return to: Advances in the Management of MS: A Reappraisal of Disease Progression and Treatment Strategies

CPD Information Download Slides

Print
Like Tweet

References

Faculty and Disclosures

Steering Committee and Faculty

Jiwon Oh, MD, PhD, FRCPC

Amit Bar-Or, MD, FRCPC

Virginia Devonshire, MD, FRCPC

Editors

Leanne Fairley, BJ Hon

Christin Melton, ELS

Content Reviewer

Amy Bernard, MS, BSN, RN-BC, CHCP

CPD

Advances in the Management of MS: A Reappraisal of Disease Progression and Treatment Strategies

Target Audience and Goal Statement

Disclosures

Steering Committee and Faculty

Jiwon Oh, MD, PhD, FRCPC

Amit Bar-Or, MD, FRCPC

Virginia Devonshire, MD, FRCPC

Editors

Leanne Fairley, BJ Hon

Christin Melton, ELS

Content Reviewer

Amy Bernard, MS, BSN, RN-BC, CHCP

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Advances in the Management of MS: A Reappraisal of Disease Progression and Treatment Strategies