This site is intended for healthcare professionals
Multiple Sclerosis (MS) Learning Zone
Declaration of sponsorship Novartis Pharma AG

Understanding MS

Declaration of sponsorship Novartis Pharma AG
Read time: 45 mins
Last updated:20th Dec 2021
Published:12th Aug 2021

What is your understanding of multiple sclerosis (MS)? Recognise the unmet needs of people with MS and understand the core principles of optimal MS management.

  • Discover clear strategies to enable shared decision-making between people with MS and their doctor
  • Learn why holistic care can be more effective than treating physical symptoms alone
  • How early should we be using high-efficacy therapies (HET)? And what is the impact for people not treated with HET? Continue on to learn more

Unmet needs in multiple sclerosis

Learn about the complex, unmet needs of people living with multiple sclerosis (MS), and how busy clinicians can meet them following best-practice strategies.

  • Many clinicians are aware that people with MS have unmet needs, but some of these may persist undetected. Learn more about the complex unmet needs in people with MS.
  • How do people with MS benefit from shared decision-making? Novartis-sponsored content in this section covers the many benefits of enabling people to make informed care decisions.
  • Below, discover the clinical actions that can help meet unmet needs in both patients and clinicians; they are diverse and sometimes surprising

Multiple sclerosis

MS is an autoimmune disease characterised by inflammation and damage to the central nervous system (CNS). Common MS symptoms include impairments to cognition, walking, and balance; bladder or bowel dysfunction; abnormal tiredness; or visual disturbances1. The symptoms of MS are caused by peripherally driven inflammation and neurodegeneration of the CNS2–5.

MS is characterised by four disease courses or phenotypes6,7:

  • clinically isolated syndrome (CIS)
  • relapsing-remitting MS (RRMS)
  • secondary progressive MS (SPMS)
  • primary-progressive MS (PPMS)

PPMS differs in important ways from RRMS and SPMS, discussed below, and can be considered apart from relapsing forms of the disease7.

The onset of MS is typically marked by CIS, which is the first episode of neurological symptoms caused by inflammation or demyelination in the CNS. CIS, which must persist for at least 24 hours, does not yet satisfy diagnostic criteria for MS as people who experience CIS may or may not develop MS8. RRMS, however can develop from CIS2,3,7.

Approximately 85% of people with MS are initially diagnosed with RRMS8. RRMS is characterised by clearly defined episodes of new or increasing neurologic symptoms (‘relapses’, ‘exacerbations’), followed by periods of partial or complete recovery (‘remissions’)7. RRMS can be characterised as ‘active’ (with relapses and/or evidence of new magnetic resonance imaging [MRI] activity over a period of time) or ‘not active’, and ‘worsening’ (a confirmed increase in disability following a relapse), or ‘not worsening’7.

SPMS follows an initial relapsing-remitting course. Some people with RRMS transition to a secondary progressive course, which shows progressive worsening of neurologic function (accumulation of disability) over time. SPMS can be characterised as ‘active’ (with relapses and/or evidence of new MRI activity during a period of time) or ‘not active’, and ‘with progression’ (evidence of disability accumulation over time, with or without relapses or new MRI activity), or ‘without progression’7.

Following 6–10 years from MS onset, approximately 25%–40% of people with RRMS have progressed to SPMS, with a median time to transition ranging from 10 to 23 years9–12

PPMS is characterised by worsening neurologic function from symptom onset, without early relapses or remissions. PPMS can be described as ‘active’ (with an occasional relapse and/or evidence of new MRI activity over time), or ‘not active’, and ‘with progression’ or ‘without progression’7.

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Management of multiple sclerosis

Consider these Novartis-resources on best-practice management of multiple sclerosis (MS).

  • What are the main diagnostic criteria of MS? Learn how diagnosis of MS is supported by magnetic resonance imaging (MRI), and lumbar puncture
  • We provide an answer to a core question in MS care: why are medications to treat MS most effective during the early, inflammatory phase of MS, becoming less efficacious as MS advances?
  • Explore the benefits of continuous symptom management with improvements to patient comfort, safety, quality of life, and more – see below

Introduction

Multiple sclerosis (MS) is an immune-mediated disease, caused by peripherally driven inflammation and neurodegeneration of the central nervous system (CNS)2–5.

As MS progresses, lesions in the CNS and the brain indicate advancement from neuroinflammation to neurodegeneration, leading to irreversible neuroaxonal degeneration, demyelination, and cumulative disability, diminishing mobility, cognitive decline, and loss of independence2–5.

MS disease phenotypes comprise clinically isolated syndrome (CIS), relapsing remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS)6,7. Approximately 85% of people with MS are diagnosed with RRMS8. As described in the previous section, PPMS differs from relapsing MS phenotypes (RRMS, SPMS) in important ways. Almost 15% of people with MS are diagnosed with PPMS7.

Follow the link to learn some of the important differences between PPMS and relapsing forms of MS

The development of relapsing forms of MS, excluding PPMS, is shown in Figure 223.

 

T1_MS_Fig2.2.png

Figure 2. Evolution of relapsing forms of multiple sclerosis (RRMS, SPMS) (Adapted24–28). CIS, clinically isolated syndrome; CNS, central nervous system; GM, grey matter; MRI, magnetic resonance imaging; MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; WM, white matter.

Referral timing and pathways

Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

References

  1. Gross HJ, Watson C. Characteristics, burden of illness, and physical functioning of patients with relapsing-remitting and secondary progressive multiple sclerosis: A cross-sectional US survey. Neuropsychiatr Dis Treat. 2017;13:1349–1357.
  2. Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, et al. Multiple sclerosis. Nat Rev Dis Prim. 2018;4(1):1–27.
  3. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nature Reviews Immunology. 2015;15(9):545–558.
  4. Baecher-Allan C, Kaskow BJ, Weiner HL. Multiple Sclerosis: Mechanisms and Immunotherapy. Neuron. 2018;97(4):742–768.
  5. Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. The Lancet Neurology. 2015;14(4):406–419.
  6. NICE. Multiple sclerosis in adults: management. 2019. https://www.nice.org.uk/guidance/cg186. Accessed 18 May 2021.
  7. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology. 2014;83(3):278–286.
  8. National Multiple Sclerosis Society. Types of MS. New York. 2020. https://www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed 17 May 2021.
  9. Scalfari A, Neuhaus A, Daumer M, Muraro PA, Ebers GC. Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014;85(1):67–75.
  10. Koch M, Kingwell E, Rieckmann P, Tremlett H, Adams D, Craig D, et al. The natural history of secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2010;81(9):1039–1043.
  11. Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: Current knowledge and future challenges. Lancet Neurology. 2006;5(4):343–354.
  12. Tremlett H, Zhao Y, Devonshire V. Natural history of secondary-progressive multiple sclerosis. Mult Scler. 2008;14(3):314–324.
  13. Kister I, Bacon TE, Chamot E, Salter AR, Cutter GR, Kalina JT, et al. Natural history of multiple sclerosis symptoms. Int J MS Care. 2013;15(3):146–158.
  14. MS International Federation. Atlas of MS background. 2013. http://www.msif.org/about-us/advocacy/atlas/atlas-of-ms/. Accessed 17 May 2021.
  15. Mehr SR, Zimmerman MP. Reviewing the unmet needs of patients with multiple sclerosis. Am Heal Drug Benefits. 2015;8(8):426–431.
  16. Rieckmann P, Centonze D, Elovaara I, Giovannoni G, Havrdová E, Kesselring J, et al. Unmet needs, burden of treatment, and patient engagement in multiple sclerosis: A combined perspective from the MS in the 21st Century Steering Group. Mult Scler Relat Disord. 2018;19:153–160.
  17. Davies F, Wood F, Brain KE, Edwards M, Jones R, Wallbank R, et al. The transition to secondary progressive multiple sclerosis: An exploratory qualitative study of health professionals’ experiences. Int J MS Care. 2016;18(5):257–264.
  18. Borreani C, Bianchi E, Pietrolongo E, Rossi M, Cilia S, Giuntoli M, et al. Unmet needs of people with severe multiple sclerosis and their carers: Qualitative findings for a home-based intervention. PLoS One. 2014;9(10):e109679.
  19. Lonergan R, Kinsella K, Fitzpatrick P, Duggan M, Jordan S, Bradley D, et al. Unmet needs of multiple sclerosis patients in the community. Mult Scler Relat Disord. 2015;4(2):144–150.
  20. Ponzio M, Tacchino A, Vaccaro C, Traversa S, Brichetto G, Battaglia MA, et al. Unmet needs influence health-related quality of life in people with multiple sclerosis. Mult Scler Relat Disord. 2020;38:101877.
  21. Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):789–800.
  22. Rae-Grant A, Day GS, Marrie RA, Rabinstein A, Cree BAC, Gronseth GS, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):777–788.
  23. Ziemssen T, Derfuss T, de Stefano N, Giovannoni G, Palavra F, Tomic D, et al. Optimizing treatment success in multiple sclerosis. Journal of Neurology. 2016;263(6):1053–1065.
  24. Cree BAC, Hollenbach JA, Bove R, Kirkish G, Sacco S, Caverzasi E, et al. Silent progression in disease activity–free relapsing multiple sclerosis. Ann Neurol. 2019;85(5):653–666.
  25. Larochelle C, Uphaus T, Prat A, Zipp F. Secondary Progression in Multiple Sclerosis: Neuronal Exhaustion or Distinct Pathology? Trends in Neurosciences. 2016;39(5):325–339.
  26. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005;128(11):2705–2712.
  27. Bar-Or A. The immunology of multiple sclerosis. Seminars in Neurology. 2008;28(1):29–45.
  28. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. The Lancet Neurology. 2015;14(2):183–193.
  29. Hobart J, Bowen A, Pepper G, Crofts H, Eberhard L, Berger T, et al. International consensus on quality standards for brain health-focused care in multiple sclerosis. Mult Scler J. 2019;25(13):1809–1818.
  30. Lorefice L, Fenu G, Frau J, Coghe G, Marrosu MG, Cocco E. The impact of visible and invisible symptoms on employment status, work and social functioning in Multiple Sclerosis. Work. 2018;60(2):263–270.
  31. Giovannoni G, Butzkueven H, Dhib-Jalbut S, Hobart J, Kobelt G, Pepper G, et al. Brain health: time matters in multiple sclerosis. Multiple Sclerosis and Related Disorders. 2016;9:S5–S48.
  32. Byatt N, Rothschild AJ, Riskind P, Ionete C, Hunt AT. Relationships Between Multiple Sclerosis and Depression. J Neuropsychiatry Clin Neurosci. 2011;23(2):198–200.
  33. Shull C, Hoyle B, Iannotta C, Fletcher E, Curan M, Cipollone V. A current understanding of multiple sclerosis. JAAPA. 2020;33(2):19–23.
  34. Siva A. Common Clinical and Imaging Conditions Misdiagnosed as Multiple Sclerosis: A Current Approach to the Differential Diagnosis of Multiple Sclerosis. Neurologic Clinics. 2018;36(1):69–117.
  35. Marriott JJ. Safety and Efficacy of Fingolimod in Treatment-Naïve Multiple Sclerosis Patients. J Cent Nerv Syst Dis. 2011;3:JCNSD.S5120.
  36. Mortensen GL, Rasmussen P V. The impact of quality of life on treatment preferences in multiple sclerosis patients. Patient Prefer Adherence. 2017;11:1789–1796.
  37. Toscano S, Patti F. CSF biomarkers in multiple sclerosis: beyond neuroinflammation. Neuroimmunol Neuroinflammation. 2020;2020(1):14–41.
  38. Kapoor R, Smith KE, Allegretta M, Arnold DL, Carroll W, Comabella M, et al. Serum neurofilament light as a biomarker in progressive multiple sclerosis. Neurology. 2020;95(10):436–444.
  39. Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. Journal of Neuroinflammation. 2019;16(1):1–11.
  40. Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, et al. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857–870.
  41. Ferreira-Atuesta C, Reyes S, Giovanonni G, Gnanapavan S. The Evolution of Neurofilament Light Chain in Multiple Sclerosis. Frontiers in Neuroscience. 2021;15:383.
  42. Kuhle J, Kropshofer H, Haering DA, Kundu U, Meinert R, Barro C, et al. Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology. 2019;92(10):E1007–E1015.
  43. Jakimovski D, Kuhle J, Ramanathan M, Barro C, Tomic D, Hagemeier J, et al. Serum neurofilament light chain levels associations with gray matter pathology: a 5-year longitudinal study. Ann Clin Transl Neurol. 2019;6(9):1757–1770.
  44. Dalla Costa G, Martinelli V, Sangalli F, Moiola L, Colombo B, Radaelli M, et al. Prognostic value of serum neurofilaments in patients with clinically isolated syndromes. Neurology. 2019;92(7):E733–E741.
  45. Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020;383(6):546–557.
  46. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541(7638):481–487.
  47. Högel H, Rissanen E, Vuorimaa A, Airas L. Positron emission tomography imaging in evaluation of MS pathology in vivo. Mult Scler J. 2018;24(11):1399–1412.
  48. Abdelhak A, Huss A, Kassubek J, Tumani H, Otto M. Serum GFAP as a biomarker for disease severity in multiple sclerosis. Sci Rep. 2018;8(1):14798.
  49. Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263–1273.
  50. AAN. 2020 AAN Annual Meeting Science Program. 2020. https://issuu.com/americanacademyofneurology/docs/aan_science2020_book. Accessed 18 June 2021.
  51. Gartner J, Hauser S, Bar-Or A, Montalban X, Cohen J, Cross AH, et al. Benefit-risk of ofatumumab in treatment-naïve early relapsing multiple sclerosis patients. In: Multiple Sclerosis Journal. 2020: 210.
  52. Turner B, Cree BAC, Kappos L, Montalban X, Papeix C, Wolinsky JS, et al. Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis. J Neurol. 2019;266(5):1182–1193.
  53. He A, Merkel B, Brown JWL, Zhovits Ryerson L, Kister I, Malpas CB, et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020;19(4):307–316.
  54. Strober LB, Becker A, Randolph JJ. Role of positive lifestyle activities on mood, cognition, well-being, and disease characteristics in multiple sclerosis. Appl Neuropsychol. 2018;25(4):304–311.
  55. Senders A, Wahbeh H, Spain R, Shinto L. Mind-body medicine for multiple sclerosis: A systematic review. Autoimmune Diseases. 2012;1(1). doi:10.1155/2012/567324.
  56. Harding K, Williams O, Willis M, Hrastelj J, Rimmer A, Joseph F, et al. Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients with Multiple Sclerosis. JAMA Neurol. 2019;76(5):536–541.
  57. Grandmaison F, Yeung M, Morrow S, Lee L, Emond F, Ward B, et al. Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis: Perspectives and approaches. Neural Regeneration Research. 2018;13(11):1871–1874.
  58. Stankiewicz JM, Weiner HL. An argument for broad use of high efficacy treatments in early multiple sclerosis. Neurology(R) neuroimmunology & neuroinflammation. 2020;7(1):636.
  59. Fyfe I. Progressive and aggressive MS — new frontiers emerge. Nat Res 2021. 2018;(December):2018.
  60. MSD. Molecular Components of the Immune System - Immunology; Allergic Disorders. 2021. https://www.msdmanuals.com/en-gb/professional/immunology-allergic-disorders/biology-of-the-immune-system/molecular-components-of-the-immune-system. Accessed 17 June 2021.
  61. Gilden D, Devlin M, Wroblewska Z. A technique for the elution of cell‐surface antibody from human brain tissue. Ann Neurol. 1978;3(5):403–405.
  62. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann Neurol. 2000;47(6):707–717.
  63. Dobson R, Ramagopalan S, Davis A, Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: A meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013;84(8):909–914.
  64. Reder AT, Centonze D, Naylor ML, Nagpal A, Rajbhandari R, Altincatal A, et al. COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies. CNS Drugs. 2021;35(3):317–330.
  65. Flores-Gonzalez RE, Hernandez J, Tornes L, Rammohan K, Delgado S. Development of SARS-CoV-2 IgM and IgG antibodies in a relapsing multiple sclerosis patient on ofatumumab. Multiple Sclerosis and Related Disorders. 2021;49:102777.
  66. Lee DSW, Rojas OL, Gommerman JL. B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nat Rev Drug Discov 2020 203. 2020;20(3):179–199.
  67. Soelberg Sorensen P, Giovannoni G, Montalban X, Thalheim C, Zaratin P, Comi G. The Multiple Sclerosis Care Unit. Mult Scler J. 2019;25(5):627–636.
  68. Canning KL, Hicks AL. Physician referral improves adherence to the physical activity guidelines for adults with MS: A randomized controlled trial. Mult Scler Relat Disord. 2020;37. doi:10.1016/j.msard.2019.101441.
Register for free access to this exclusive healthcare learning resource


Why sign up with Medthority?

Develop your knowledge with our disease and condition focused Learning Zones

Access content from credible sources, including expert-led commentary, videos, podcasts, and webinars as well as clinical trials, treatment information and guidelines 

Personalised dashboard providing updates and recommendations for content within your areas of interest

Welcome: