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About This Activity

Activity Description and Learning Objectives

In this activity, experts in neurology discuss how greater understanding of multiple sclerosis (MS) pathophysiology is vital to guide the choice of current and emerging therapies, as well as providing an individualized approach for optimal outcomes in patients with relapsing-remitting MS.

This activity has been jointly provided by Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

After watching this activity, participants should be better able to:

Target Audience

This activity is designed to meet the educational needs of neurologists, specialist nurses, radiologists and other healthcare professionals (HCPs) who form the multidisciplinary team (MDT) managing the care of patients with MS worldwide, with a focus on Europe and North America.

Faculty Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Prof. Cris Constantinescu disclosures: Speaker honoraria: Biogen, Merck, Novartis, Teva
Consultancy: Biogen, Merck, Teva. Research support: Bayer, Biogen, Genzyme, GW Pharmaceuticals, Merck, Roche, Sanofi Pasteur/MSD, Teva

Prof. Aksel Siva disclosures: Speaker honoraria/consultancy/advisory boards: Bayer, Biogen Idec/Gen Pharma Turkey, F Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi-Genzyme, Teva

Prof. Xavier Montalban disclosures: Speaker honoraria/advisory boards/clinical trial steering committee from Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Genzyme, Immunic, Medday, Merck, Mylan, Nervgen, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceuticals, TG Therapeutics, Excemed, MSIF and NMSS. Research support through St. Michael’s Hospital from Abbvie, Biogen, Medday, Roche and Sanofi; through Multiple Sclerosis Centre of Catalonia (Cemcat) from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva Pharmaceuticals

Content Reviewer

Walter Murray Yarbrough, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Kathy Day has no financial interests/relationships or affiliations in relation to this activity.

Requirement for Successful Completion

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™️. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: May 25, 2020. Date credits expire: May 25, 2021.

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Q1. Which of the following immune cells is thought to contribute to MS pathogenesis by generating antibodies, while also regulating immune processes by regulating pro-inflammatory cytokines?

  1. A. B cells
  2. B. T cells
  3. C. Natural killer cells
  4. D. Microglial cells

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B cells and different effector T-cell populations of the adaptive immune system, together with natural killer and microglial cells of the innate immune system, play unique roles in contributing to the disease.1 B cells influence the pathogenesis of MS through antigen presentation, autoantibody production or cytokine secretion.2
Abbreviations
MS, multiple sclerosis.

References

  1. Høglund RA, Maghazachi AA. Multiple sclerosis and the role of immune cells. World J Exp Med 2014;4:27–37.
  2. Montalban X, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med 2017;376: 209–220.

Q2. Which of the following statements best describes the data supporting the use of BTK inhibitors in patients with MS?

  1. A. BTK inhibition leads to widespread B-cell depletion
  2. B. BTK inhibition is associated with some (NS) reduction in disease activity compared to placebo
  3. C. BTK inhibition may lead to clinically relevant decreases in the annualized relapse rate
  4. D. BTK inhibition is not associated with any clinically relevant adverse events

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Evobrutinib and SAR442168, are selective oral BTK inhibitors have been shown to inhibit B-cell activation without widespread B-cell depletion and associated side effects.1 The Phase II trials for these agents have both met their primary endpoints, demonstrating significantly fewer enhancing lesions.2,3 Evobrutinib also resulted in a clinically relevant decrease in the annualized relapse rate compared to placebo over 48 weeks, but was associated with increased liver enzymes.2 Phase III trials are ongoing.
Abbreviations
BTK, Bruton’s tyrosine kinase; NS, not significant

References

  1. Kolahdouzan M, et al. Novel molecular leads for the prevention of damage and the promotion of repair in neuroimmunological disease. Front Immunol 2019;10:1657.
  2. Montalban X, et al. Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis. N Engl J Med 2019;380:2406–2417.
  3. Clinicaltrials.gov. Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis. Available from: https://clinicaltrials.gov/ct2/show/NCT03889639 (Accessed May 20).

Q3. Which of the following patients with MS might be considered as a good candidate for induction therapy with high-efficacy DMT?

  1. A. A young patient who presents with a clinically isolated syndrome
  2. B. A patient with clinically stable MS on oral DMT
  3. C. A newly diagnosed patient with recent relapses and EDSS of 3
  4. D. A patient who is having problems being adherent with current DMT

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A number of negative prognostic factors have been identified that can help to identify patients at risk of a more aggressive disease course. The main criteria for identifying a potential good candidate for induction treatment have been recognised as: a younger age, at least two relapses within the previous 12 months, a severe relapse resulting in an EDSS score ≥2 (or a score increase of 2 or more points) within the previous 12 months and the presence of two or more additional Gd-enhancing lesions on a recent MRI scan.1

Abbreviations

EDSS, Expanded Disability Status Scale; Gd, gadolinium; MS, multiple sclerosis.

References

  1. Ruggieri S et al. Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives. Mult Scler Demyelinating Disord 2018;3:5.

Q4. You have a male patient who is 53 years of age with highly active MS. He has experienced several relapses in the last 12 months, with short intervals between attacks, has more than 2 Gd-enhancing lesions and has an EDSS score of 4.0. Which of the following treatment strategies would you consider as a first-line option in this patient?

  1. A. Induction therapy with high-potency DMTs (e.g. alemtuzumab, natalizumab)
  2. B. Induction therapy with intermediate-potency DMTs (e.g. fingolimod, dimethyl fumarate)
  3. C. Escalation therapy with first-line DMTs (e.g. interferon beta, glatiramer acetate)

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This patient has clinical and radiological features suggestive of aggressive disease. In this type of patient, induction therapy with high-potency DMTs such as alemtuzumab and natalizumab is recommended, taking into account patient characteristics and comorbidities and the safety profile of the selected agent.1 In an international cohort study, alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity.2 A systematic review found alemtuzumab, ocrelizumab, natalizumab and fingolimod had a relatively higher response and lower dropout rates than did the other DMTs.3

Abbreviations

EDSS, Expanded Disability Status Scale; Gd, gadolinium; MS, multiple sclerosis.

References

  1. Montalban X, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler J 2018;24: 96–120.
  2. Kalincik T, et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study. Lancet Neurology 2017;16:271–281.
  3. Li H, et al. Comparative efficacy and acceptability of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis. J Neurol 2019; Available from: https://doi.org/10.1007/s00415-019-9395-w
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touchEXPERT OPINIONS

How do we personalize treatment of multiple sclerosis in the light of recent advances?

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Introduction

Watch leading experts involved in the care of patients with multiple sclerosis (MS) discuss how recent advances in understanding of MS pathophysiology may drive treatment choices, now and in the future.

This activity is intended for neurologists, specialist nurses, radiologists and other healthcare professionals who form the multidisciplinary team managing the care of patients with MS worldwide, with a focus on Europe and North America.

Learning Objectives

After watching this touchEXPERT OPINIONS, you should be able to:

  • Recall the disease mechanisms contributing to the progression of MS
  • Interpret the role of induction therapy in real-world clinical practice
  • Recognize the importance of BTK as a potential future treatment target in MS