Neurol. praxi. 2023;24(3):218-221 | DOI: 10.36290/neu.2023.040

B-cell targeted therapy to impact the progression of multiple sclerosis

MUDr. Martin Elišák, Ph.D.
Neurologická klinika 2. LF UK a FN Motol, Praha

Monoclonal antibodies against CD20+ lymphocytes represent a highly effective treatment of multiple sclerosis by rapidly suppressing activity conditioned mainly by inflammatory processes. The progressive component of the disease presents a therapeutically more difficult problem - inflammation compartmentalizes beyond the blood-brain barrier, inflammation becomes diffuse, and degenerative processes play a role. Although the best effect of treatment is when it is started as early as possible, some patients may have progression from the beginning of the disease or are diagnosed at an advanced stage of the disease. Depletion of CD20+ lymphocytes may delay or slow progression in these patients. The aim of this article is to summarize the pathophysiology, the possibilities of influencing the progression of B lymphocyte depletion, the results of clinical trials and future directions in the treatment of progressive multiple sclerosis.

Keywords: multiple sclerosis, progression, monoclonal antibodies against CD20+ lymphocytes.

Received: May 22, 2023; Revised: May 22, 2023; Accepted: June 5, 2023; Prepublished online: June 5, 2023; Published: June 14, 2023  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Elišák M. B-cell targeted therapy to impact the progression of multiple sclerosis. Neurol. praxi. 2023;24(3):218-221. doi: 10.36290/neu.2023.040.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Anolik JH, Campbell D, Felgar RE, et al. TherelationshipofFcgammaRIIIa genotype to degreeof B cell depletion by rituximab in thetreatmentofsystemic lupus erythematosus. Arthritis and rheumatism. 2003;48(2):455-459. Go to original source... Go to PubMed...
    2. Barkhof F, Kappos L, Wolinsky JS, et al. Onset of clinical and MRI efficacy of ocrelizumab in relapsing multiple sclerosis. Neurology. 2019;93(19):e1778-e1786. Go to original source... Go to PubMed...
    3. Bar­‑Or A, O'Brien SM, Sweeney ML, et al. Clinical Perspectives on the Molecular and Pharmacological Attributesof Anti­‑CD20 Therapies for Multiple Sclerosis. CNS drugs. 2021;35(9):985-997. Go to original source... Go to PubMed...
    4. Bhargava P, Wicken C, Smith MD, et al. Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement. Multiple sclerosis and related disorders. 2019;30:136-140. Go to original source... Go to PubMed...
    5. Correale J, Gaitán MI, Ysrraelit MC, et al. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain: a journal of neurology. 2017;140(3):527-546.
    6. Disanto G, Barro C, Benkert P, et al. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Annals of neurology. 2017;81(6):857-870. Go to original source... Go to PubMed...
    7. Fereidan­‑Esfahani M, Brück W, Weber MS. Targeting Central Nervous System B Cells in Progression of Multiple Sclerosis: Is Intrathecal Anti­‑CD20 a Therapeutic Option? JAMA neurology. 2015;72(12):1407-1408. Go to original source... Go to PubMed...
    8. Filippi M, Preziosa P, Langdon D, et al. Identifying Progression in Multiple Sclerosis: New Perspectives. Annals of neurology. 2020;88(3):438-452. Go to original source... Go to PubMed...
    9. Giovannoni G, Kappos L, de Seze J, et al. Long­‑Term Reduction of Relapse Rate and Confirmed Disability Progression after 7.5 Years of Ocrelizumab Treatment in Patients with Relapsing Multiple Sclerosis in the OPERA OLE. ECTRIMS 2021.
    10. Hauser SL, Kappos L, Montalban, et al. Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary Progressive Multiple Sclerosis. ECTRIMS 2021. Go to original source...
    11. Hauser SL, Bar­‑Or A, Comi G, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. The New England journa lof medicine. 2017;376(3):221-234. Go to original source... Go to PubMed...
    12. Hauser SL, Bar­‑Or A, Weber MS, et al. Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis. Neurology(R) neuroimmunology & neuroinflammation. 2023;10(2):e20094. DOI: 10.1212/NXI.0000000000200094. Go to original source... Go to PubMed...
    13. Havla J, Hohlfeld R. Antibody Therapies for Progressive Multiple Sclerosis and for Promoting Repair. Neurotherapeutics: the journal of the American Society for Experimental Neuro Therapeutics. 2022;19(3):774-784. Go to original source... Go to PubMed...
    14. Healy BC, Glanz BI, Swallow E, et al. Confirmed disability progressionprovides limited predictive information regarding future disease progression in multiple sclerosis. Multiple sclerosis journal - experimental, translational and clinical. 2021;7(2): 2055217321999070. Go to original source... Go to PubMed...
    15. Hohlfeld R, Dornmair K, Meinl E, et al. The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse­‑translational research. Lancet neurology. 2016:15(3):317-331. Go to original source... Go to PubMed...
    16. Kappos L, HartungHEp, Hauser SL, et al. Eight­‑Year Analyses of Repeated Confirmed Disability Progressions in the OPERA I/II and ORATORIO Studies and Their Open­‑Label Extensions. ECTRIMS 2022. Go to original source...
    17. Kappos L, Wolinsky JS, Giovannoni G, et al. Ocrelizumab reduces disability progression independent of relapse activity in patients with relapsing multiple sclerosis (RMS) (ENCORE). Journal of Neurology, Neurosurgery, and Psychiatry. 2018;89(6):A25.2-A25. Go to original source...
    18. Kuhlmann T, Moccia M, Coetzee T, et al. Multiple sclerosis progression: time for a new mechanism­‑driven framework. Lancet neurology. 2023; 22(1):78-88. Go to original source... Go to PubMed...
    19. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014; 83(3): 278-286. Go to original source... Go to PubMed...
    20. Martin M del P, Cravens PD, Winger R, et al. Depletionof B lymphocytes from cerebral perivascular spaces by rituximab. Archives of neurology. 2009;66(8):1016-1020. Go to original source... Go to PubMed...
    21. Meinl E, Hohlfeld R. CD20 T Cells as Pathogenic Players and Therapeutic Targets in MS. Annals of neurology. 2021;90(5): 722-724. Go to original source... Go to PubMed...
    22. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. The New England journal of medicine. 2017;376(3):209-220. Go to original source... Go to PubMed...
    23. Montalban X, Matthews PM, Simpson A, et al. Real­‑world evaluation of ocrelizumab in multiple sclerosis: a systematic review. Annals of clinical and translational neurology. 2023;10(3):302-311. Go to original source... Go to PubMed...
    24. Obermeier B, Mentele R, Malotka J, et al. Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Naturemedicine. 2008;14(6):688-693. Go to original source... Go to PubMed...
    25. Portaccio E, Bellinvia A, Fonderico M, et al. Progressionis independent of relapse activity in early multiple sclerosis: a real­‑lifecohort study. Brain: a journal of neurology. 2022;145(8):2796-2805. Go to original source... Go to PubMed...
    26. Preziosa P, Rocca MA, Filippi M. Currentstate­‑of­‑art of the application of serum neurofilaments in multiple sclerosis diagnosis and monitoring. Expert review of neurotherapeutics. 2022;20(8):747-769. Go to original source... Go to PubMed...
    27. Rubenstein JL, Combs D, Rosenberg J, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003;101(2):466-468. Go to original source... Go to PubMed...
    28. Turner B, Cree BAC, Kappos L, et al. Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis. Journal of neurology. 2019;266(5):1182-1193. Go to original source... Go to PubMed...
    29. Wolinsky JS, Montalban X, Hauser SL, et al. Evaluation of no evidence of progression oractive disease (NEPAD) in patients with primary progressive multiple sclerosis in the ORATORIO trial. Annals of neurology. 2018;84(4):527-536. Go to original source... Go to PubMed...
    30. Wolinsky JS, Vermersch P, Hartung HP, et al SustainedReduction in 48-Week Confirmed Disability Progression in Patientswith PPMS Treated with Ocrelizumab in the ORATORIO OLE: 8-YearFollow­‑Up. ECTRIMS 2022.

    Return to the content


    Neurology for Practice

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.