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Be aware that the benefits of biological drugs in multiple sclerosis may be offset by their capacity to cause immunological complications

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Abstract

Biological immunotherapies for multiple sclerosis (MS) include recombinant proteins (preparations of interferon-β) and monoclonal antibodies (e.g. natalizumab, alemtuzumab, ocrelizumab and off-label rituximab). They have shown unprecedented efficacy in the treatment of MS; however, they are all immunogenic and have been associated with immunological complications, such as neutralizing immunogenicity, secondary immunodeficiency and secondary autoimmunity.

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References

  1. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–80.

    Article  CAS  Google Scholar 

  2. Soleimani B, Murray K, Hunt D. Established and emerging immunological complications of biological therapeutics in multiple sclerosis. Drug Saf. 2019;42(8):941–56.

    Article  CAS  Google Scholar 

  3. Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011;378(9805):1779–87.

    Article  CAS  Google Scholar 

  4. Hauser SL, Belachew S, Kappos L. Ocrelizumab in primary progressive and relapsing multiple sclerosis. N Engl J Med. 2017;376(17):1694.

    PubMed  Google Scholar 

  5. Hesse D, Sellebjerg F, Sorensen PS. Absence of MxA induction by interferon β in patients with MS reflects complete loss of bioactivity. Neurology. 2009;73(5):372–7.

    Article  CAS  Google Scholar 

  6. Polman CH, Bertolotto A, Deisenhammer F, et al. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis. Lancet Neurol. 2010;9(7):740–50.

    Article  CAS  Google Scholar 

  7. Farrell RA, Giovannoni G. Measuring and management of anti-interferon beta antibodies in subjects with multiple sclerosis. Mult Scler. 2007;13:567–77.

    Article  CAS  Google Scholar 

  8. Kolb-Maurer A, Goebeler M, Maurer M. Cutaneous adverse events associated with interferon-β treatment of multiple sclerosis. Int J Mol Sci. 2015;16(7):14951–60.

    Article  Google Scholar 

  9. Vennegoor A, Rispens T, Strijbis EM, et al. Clinical relevance of serum natalizumab concentration and anti-natalizumab antibodies in multiple sclerosis. Mult Scler. 2013;19(5):593–600.

    Article  CAS  Google Scholar 

  10. Clerico M, Artusi CA, Di Liberto A, et al. Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis. Expert Opin Drug Saf. 2017;16(8):963–72.

    Article  CAS  Google Scholar 

  11. Antezana A, Sigal S, Herbert J, et al. Natalizumab-induced hepatic injury: a case report and review of literature. Mult Scler Relat Disord. 2015;4(6):495–8.

    Article  CAS  Google Scholar 

  12. Ho PR, Koendgen H, Campbell N, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol. 2017;16(11):925–33.

    Article  CAS  Google Scholar 

  13. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.

    Article  CAS  Google Scholar 

  14. Alping P, Frisell T, Novakova L, et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Ann Neurol. 2016;79(6):950–8.

    Article  CAS  Google Scholar 

  15. Castela E, Lebrun-Frenay C, Laffon M, et al. Evolution of nevi during treatment with natalizumab: a prospective follow-up of patients treated with natalizumab for multiple sclerosis. Arch Dermatol. 2011;147(1):72–6.

    Article  Google Scholar 

  16. Dahdaleh D, Altmann DM, Malik O, et al. Breathlessness, night sweats, and weight loss on natalizumab. Lancet. 2012;380(9843):726–7.

    Article  CAS  Google Scholar 

  17. Bergamaschi R, Montomoli C. Melanoma in multiple sclerosis treated with natalizumab: causal association or coincidence? Mult Scler. 2009;15(12):1532–3.

    Article  CAS  Google Scholar 

  18. Dubuisson N, Baker D, Kang AS, et al. Alemtuzumab depletion failure can occur in multiple sclerosis. Immunology. 2018;154(2):253–60.

    Article  CAS  Google Scholar 

  19. Moreau T, Coles A, Wing M, et al. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain. 1996;119(Pt 1):225–37.

    Article  Google Scholar 

  20. Wing MG, Moreau T, Greenwood J, et al. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcγRIII) and CD11a/CD18 (LFA-1) on NK cells. J Clin Invest. 1996;98(12):2819–26.

    Article  CAS  Google Scholar 

  21. Wing MG, Waldmann H, Isaacs J, et al. Ex-vivo whole blood cultures for predicting cytokine-release syndrome: dependence on target antigen and antibody isotype. Ther Immunol. 1995;2(4):183–90.

    CAS  PubMed  Google Scholar 

  22. Blasco MR, Ramos A, Malo CG, et al. Acute pneumonitis and pericarditis related to alemtuzumab therapy in relapsing-remitting multiple sclerosis. J Neurol. 2017;264(1):168–9.

    Article  Google Scholar 

  23. Azzopardi L, Thompson SA, Harding KE, et al. Predicting autoimmunity after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014;85(7):795–8.

    Article  Google Scholar 

  24. CAMMS223 Trial Investigators, Coles AJ, Compston DA, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.

    Article  Google Scholar 

  25. Ocrevus® (ocrelizumab): US prescribing information. South San Francisco: Genentech Inc; 2019.

  26. Dunn N, Juto A, Ryner M, et al. Rituximab in multiple sclerosis: frequency and clinical relevance of anti-drug antibodies. Mult Scler. 2018;24(9):1224–33.

    Article  CAS  Google Scholar 

  27. Kadish R, Robertson D, Sweeney M. Fatal leukoencephalopathy in a patient with multiple sclerosis following treatment with ocrelizumab. Neurology. 2018;90(15 Suppl):5.353.

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    The article was adapted from Drug Safety 2019; 42(8):941–56 by employees of Adis International Ltd./Springer Nature, who are responsible for the article content and declare no conflicts of interest.

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    The preparation of this review was not supported by any external funding.

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    Adis Medical Writers. Be aware that the benefits of biological drugs in multiple sclerosis may be offset by their capacity to cause immunological complications. Drugs Ther Perspect 36, 63–66 (2020). https://doi.org/10.1007/s40267-019-00693-x

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