Skip to main content
SpringerLink
Log in

Adverse events and monitoring requirements associated with monoclonal antibody therapy in patients with multiple sclerosis

  • Therapy in Practice
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

Multiple sclerosis (MS) is treated with a variety of immunomodulatory and immunosuppressive drugs. Among the most potent therapeutic options are monoclonal antibodies (MAbs). So far, the MAbs natalizumab, alemtuzumab, and ocrelizumab have been approved for MS treatment. While their efficacy is indisputable, these drugs have safety issues not seen with previous MS drugs. MAbs are the ideal class of treatment for many patients with MS, but neurologists prescribing these MAbs need to be aware of their potential risks and monitor patients closely. Although rare, adverse events associated with MAbs may be fatal; opportunistic infections, tumors, and infusion-related events require planning and monitoring of patients before, during, and after MAb therapy. This review summarizes the type and management of adverse events associated with MAb treatment in patients with MS, and emphasizes the importance of evidence-based knowledge for all neurologists involved in MS therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Vargas DL, Tyor WR. Update on disease-modifying therapies for multiple sclerosis. J Investig Med. 2017;65(5):883–91.

    PubMed  Google Scholar 

  2. Hartung DM. Economics and cost-effectiveness of multiple sclerosis therapies in the USA. Neurotherapeutics. 2017;14(4):1018–26.

    PubMed  PubMed Central  Google Scholar 

  3. Merkel B, Butzkueven H, Traboulsee AL, et al. Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: a systematic review. Autoimmun Rev. 2017;16(6):658–65.

    PubMed  Google Scholar 

  4. McGinley MP, Moss BP, Cohen JA. Safety of monoclonal antibodies for the treatment of multiple sclerosis. Expert Opin Drug Saf. 2017;16(1):89–100.

    CAS  PubMed  Google Scholar 

  5. Akaishi T, Nakashima I. Efficiency of antibody therapy in demyelinating diseases. Int Immunol. 2017;29(7):327–35.

    CAS  PubMed  Google Scholar 

  6. Pucci E, Giuliani G, Solari A, et al. Natalizumab for relapsing remitting multiple sclerosis. Cochrane Database Syst Rev. 2011;10:CD007621.

    Google Scholar 

  7. Riera R, Porfírio GJ, Torloni MR. Alemtuzumab for multiple sclerosis. Cochrane Database Syst Rev. 2016;4:CD011203.

    PubMed  Google Scholar 

  8. McCool R, Wilson K, Arber M, et al. Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis. Mult Scler Relat Disord. 2019;29:55–61.

    PubMed  Google Scholar 

  9. Shirley M. Daclizumab: a review in relapsing multiple sclerosis. Drugs. 2017;77(4):447–58.

    CAS  PubMed  Google Scholar 

  10. Judson MA, Elicker BM, Colby TV, et al. The development of sarcoidosis in patients receiving daclizumab: a case series from multiple clinical trials. Respir Med. 2019;149:23–7.

    PubMed  Google Scholar 

  11. Williams T, Chataway J. Immune-mediated encephalitis with daclizumab: the final nail. Mult Scler. 2019;25(5):753–4.

    PubMed  Google Scholar 

  12. Engelhardt B, Kappos L. Natalizumab: targeting α4-integrins in multiple sclerosis. Neurodegener Dis. 2008;5(1):16–22.

    CAS  PubMed  Google Scholar 

  13. Chataway J, Miller DH. Natalizumab therapy for multiple sclerosis. Neurotherapeutics. 2013;10(1):19–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Balasa RI, Simu M, Voidazan S, et al. Natalizumab changes the peripheral profile of the Th17 panel in MS patients: new mechanisms of action. CNS Neurol Disord Drug Targets. 2017;16(9):1018–26.

    CAS  PubMed  Google Scholar 

  15. Park SC, Jeen YT. Anti-integrin therapy for inflammatory bowel disease. World J Gastroenterol. 2018;24(17):1868–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Namey M, Halper J, O’leary S, et al. Best practices in multiple sclerosis: infusion reactions versus hypersensitivity associated with biologic therapies. J Infus Nurs. 2010;33(2):98–111.

    PubMed  Google Scholar 

  17. Ruck T, Bittner S, Wiendl H, et al. Alemtuzumab in multiple sclerosis: mechanism of action and beyond. Int J Mol Sci. 2015;16(7):16414–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Laribi K, Lemaire P, Sandrini J, et al. Advances in the understanding and management of T-cell prolymphocytic leukemia. Oncotarget. 2017;8(61):104664–86.

    PubMed  PubMed Central  Google Scholar 

  19. Zhao Y, Su H, Shen X, et al. The immunological function of CD52 and its targeting in organ transplantation. Inflamm Res. 2017;66(7):571–8.

    CAS  PubMed  Google Scholar 

  20. Martin F, Chan AC. B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol. 2006;24:467–96.

    CAS  PubMed  Google Scholar 

  21. Mayer L, Kappos L, Racke MK, et al. Ocrelizumab infusion experience in patients with relapsing and primary progressive multiple sclerosis: results from the phase 3 randomized OPERA I, OPERA II, and ORATORIO studies. Mult Scler Relat Disord. 2019;30:236–43.

    PubMed  Google Scholar 

  22. Berger JR, Koralnik IJ. Progressive multifocal leukoencephalopathy and natalizumab—unforeseen consequences. N Engl J Med. 2005;353(4):414–6.

    CAS  PubMed  Google Scholar 

  23. Nicholas JA, Racke MK, Imitola J, et al. First-line natalizumab in multiple sclerosis: rationale, patient selection, benefits and risks. Ther Adv Chronic Dis. 2014;5(2):62–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhovtis Ryerson L, Frohman TC, Foley J, et al. Extended interval dosing of natalizumab in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87(8):885–9.

    CAS  PubMed  Google Scholar 

  25. Shenoy ES, Mylonakis E, Hurtado RM, et al. Natalizumab and HSV meningitis. J Neurovirol. 2011;17(3):288–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Sharma K, Ballham SA, Inglis KE, et al. Does natalizumab treatment increase the risk of herpes simplex encephalitis in multiple sclerosis? Case and discussion. Mult Scler Relat Disord. 2013;2(4):385–7.

    PubMed  Google Scholar 

  27. Fragoso YD, Brooks JB, Gomes S, et al. Report of three cases of herpes zoster during treatment with natalizumab. CNS Neurosci Ther. 2013;19(4):280–1.

    PubMed  PubMed Central  Google Scholar 

  28. Gutwinski S, Erbe S, Münch C, et al. Severe cutaneous Candida infection during natalizumab therapy in multiple sclerosis. Neurology. 2010;74(6):521–3.

    CAS  PubMed  Google Scholar 

  29. Kobeleva X, Wegner F, Brunotte I, et al. Varicella zoster-associated retinal and central nervous system vasculitis in a patient with multiple sclerosis treated with natalizumab. J Neuroinflamm. 2014;11:19.

    Google Scholar 

  30. Valenzuela RM, Pula JH, Garwacki D, et al. Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab. J Neurol Sci. 2014;340(1–2):109–11.

    PubMed  Google Scholar 

  31. Hradilek P, Zeman D, Tudik I, et al. Asymptomatic lung disease caused by Mycobacterium kansasii as an opportunistic infection in a patient treated with natalizumab for relapsing-remitting multiple sclerosis. Mult Scler. 2014;20(5):639–40.

    PubMed  Google Scholar 

  32. Durmus B, Van Goethem J, Vercruyssen A, et al. Cerebral abscess in a multiple sclerosis patient during treatment with natalizumab. Acta Neurol Belg. 2019. https://doi.org/10.1007/s13760-019-01131-5 (Epub 2019).

    Article  PubMed  Google Scholar 

  33. Lima MR, Farias LABG, da Ponte MF, et al. Self-limited cytomegalovirus infection during natalizumab treatment for multiple sclerosis. Eur J Case Rep Intern Med. 2019;6(2):001046.

    PubMed  PubMed Central  Google Scholar 

  34. Holmoy T, von der Lippe H, Leegaard TM. Listeria monocytogenes infection associated with alemtuzumab: a case for better preventive strategies. BMC Neurol. 2017;17(1):65.

    PubMed  PubMed Central  Google Scholar 

  35. Clerico M, De Mercanti S, Artusi CA, et al. Active CMV infection in two patients with multiple sclerosis treated with alemtuzumab. Mult Scler. 2017;23(6):874–6.

    CAS  PubMed  Google Scholar 

  36. Pappolla A, Midaglia L, Boix Rodríguez CP, et al. Simultaneous CMV and Listeria infection following alemtuzumab treatment for multiple sclerosis. Neurology. 2019;92(6):296–8.

    PubMed  Google Scholar 

  37. Russo CV, Saccà F, Paternoster M, et al. Post-mortem diagnosis of invasive pulmonary aspergillosis after alemtuzumab treatment for multiple sclerosis. Mult Scler. 2019. https://doi.org/10.1177/1352458518813110 (Epub 2019).

    Article  PubMed  Google Scholar 

  38. Coles AJ, Twyman CL, Arnold DL, et al. CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39.

    CAS  PubMed  Google Scholar 

  39. Sheikh-Taha M, Corman LC. Pulmonary Nocardia beijingensis infection associated with the use of alemtuzumab in a patient with multiple sclerosis. Mult Scler. 2017;23(6):872–4.

    PubMed  Google Scholar 

  40. Penkert H, Delbridge C, Wantia N, et al. Fulminant central nervous system nocardiosis in a patient treated with alemtuzumab for relapsing-remitting multiple sclerosis. JAMA Neurol. 2016;73(6):757–9.

    PubMed  Google Scholar 

  41. Ciardi MR, Iannetta M, Zingaropoli MA, et al. Reactivation of hepatitis B virus with immune-escape mutations after ocrelizumab treatment for multiple sclerosis. Open Forum Infect Dis. 2018;6(1):ofy356.

    PubMed  PubMed Central  Google Scholar 

  42. Nicolini LA, Canepa P, Caligiuri P, et al. Fulminant hepatitis associated with echovirus 25 during treatment with ocrelizumab for multiple sclerosis. JAMA Neurol. 2019;76(7):866–7.

    PubMed  Google Scholar 

  43. Hauser SL, Bar-Or A, Comi G, et al. OPERA I and OPERA II clinical investigators. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–34.

    CAS  PubMed  Google Scholar 

  44. https://www.nationalmssociety.org/About-the-Society/News/Case-of-PML-Reported-in-Person-Receiving-Ocrevus-t.

  45. Kelm RC, Hagstrom EL, Mathieu RJ, et al. Melanoma subsequent to natalizumab exposure: a report from the RADAR (Research on Adverse Drug events And Reports) program. J Am Acad Dermatol. 2019;80(3):820–1.

    PubMed  Google Scholar 

  46. Nixon M, Menger RP, Kalakoti P, et al. Natalizumab-associated primary central nervous system lymphoma. World Neurosurg. 2018;109:152–9.

    PubMed  Google Scholar 

  47. Fragoso YD, Brooks JBB, Reghin Neto M. The unexpected finding of a hemangioblastoma on the cerebellum of a patient undergoing treatment with natalizumab for multiple sclerosis. Iran J Neurol. 2017;16(2):96–7.

    PubMed  PubMed Central  Google Scholar 

  48. Kantorova E, Bittsanský M, Sivak S, et al. Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes. BMC Cancer. 2017;17(1):424.

    PubMed  PubMed Central  Google Scholar 

  49. Gandoglia I, Ivaldi F, Carrega P, et al. In vitro VLA-4 blockade results in an impaired NK cell-mediated immune surveillance against melanoma. Immunol Lett. 2017;181:109–15.

    CAS  PubMed  Google Scholar 

  50. Lebrun C, Rocher F. Cancer risk in patients with multiple sclerosis: potential impact of disease-modifying drugs. CNS Drugs. 2018;32(10):939–49.

    CAS  PubMed  Google Scholar 

  51. Guarnera C, Bramanti P, Mazzon E. Alemtuzumab: a review of efficacy and risks in the treatment of relapsing remitting multiple sclerosis. Ther Clin Risk Manag. 2017;13:871–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Fragoso YD, Alves-Leon SV, Arruda WO, et al. Natalizumab adverse events are rare in patients with multiple sclerosis. Arq Neuropsiquiatr. 2013;71(3):137–41.

    PubMed  Google Scholar 

  53. Prosperini L, Kinkel RP, Miravalle AA, et al. Post-natalizumab disease reactivation in multiple sclerosis: systematic review and meta-analysis. Ther Adv Neurol Disord. 2019;12:1756286419837809.

    PubMed  PubMed Central  Google Scholar 

  54. Gonzalez-Suarez I, Rodríguez de Antonio L, Orviz A, et al. Catastrophic outcome of patients with a rebound after natalizumab treatment discontinuation. Brain Behav. 2017;7(4):e00671.

    PubMed  PubMed Central  Google Scholar 

  55. Frau J, Coghe G, Lorefice L, et al. Efficacy and safety of alemtuzumab in a real-life cohort of patients with multiple sclerosis. J Neurol. 2019;266(6):1405–11.

    CAS  PubMed  Google Scholar 

  56. Caon C, Namey M, Meyer C, et al. Prevention and management of infusion-associated reactions in the comparison of alemtuzumab and Rebif® efficacy in multiple sclerosis (CARE-MS) program. Int J MS Care. 2015;17(4):191–8.

    PubMed  PubMed Central  Google Scholar 

  57. Myro AZ, Bjerke G, Zarnovicky S, et al. Diffuse alveolar hemorrhage during alemtuzumab infusion in a patient with multiple sclerosis: a case report. BMC Pharmacol Toxicol. 2018;19(1):75.

    PubMed  PubMed Central  Google Scholar 

  58. Azevedo CJ, Kutz C, Dix A, et al. Intracerebral haemorrhage during alemtuzumab administration. Lancet Neurol. 2019;18(4):329–31.

    PubMed  Google Scholar 

  59. Maniscalco GT, Cerillo I, Servillo G, et al. Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature. Clin Neurol Neurosurg. 2018;175:134–6.

    CAS  PubMed  Google Scholar 

  60. https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-warns-about-rare-serious-risks-stroke-and-blood-vessel-wall-tears-multiple-sclerosis-drug. Accessed 23 Aug 2019

  61. Frey N. Cytokine release syndrome: who is at risk and how to treat. Best Pract Res Clin Haematol. 2017;30(4):336–40.

    PubMed  Google Scholar 

  62. Devonshire V, Phillips R, Wass H, et al. Monitoring and management of autoimmunity in multiple sclerosis patients treated with alemtuzumab: practical recommendations. J Neurol. 2018;265(11):2494–505.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Lambert C, Dubois B, Dive D, et al. Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus. Acta Neurol Belg. 2018;118(1):7–11.

    PubMed  PubMed Central  Google Scholar 

  64. Phelps R, Winston JA, Wynn D, et al. Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis. Mult Scler. 2019;25(9):1273–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Aouad P, Yiannikas C, Fernando SL, et al. A case of autoimmune myositis after treatment with alemtuzumab for multiple sclerosis. Mult Scler J Exp Transl Clin. 2018;4(4):2055217318819012.

    PubMed  PubMed Central  Google Scholar 

  66. Giarola B, Massey J, Barnett Y, et al. Autoimmune encephalitis following alemtuzumab treatment of multiple sclerosis. Mult Scler Relat Disord. 2019;28:31–3.

    PubMed  Google Scholar 

  67. Pisa M, Della Valle P, Coluccia A, et al. Acquired haemophilia A as a secondary autoimmune disease after alemtuzumab treatment in multiple sclerosis: a case report. Mult Scler Relat Disord. 2019;27:403–5.

    CAS  PubMed  Google Scholar 

  68. Richter S, Wagner B, Celius EG. Two cases of diabetes mellitus type 1 after alemtuzumab treatment for multiple sclerosis: another probable secondary autoimmune disease. J Neurol. 2019;266(5):1270–1.

    PubMed  Google Scholar 

  69. Hoffman BM, Zeid NA, Alam U, et al. Lambert-Eaton myasthenic syndrome associated with alemtuzumab administration. Mult Scler Relat Disord. 2019;27:131–2.

    PubMed  Google Scholar 

  70. Whiteside D, Barth S, Datta A, et al. Pneumonitis secondary to alemtuzumab in a patient with multiple sclerosis: anon-infectious cause of breathlessness. Mult Scler Relat Disord. 2018;22:139–40.

    CAS  PubMed  Google Scholar 

  71. Ruck T, Pfeuffer S, Schulte-Mecklenbeck A, et al. Vitiligo after alemtuzumab treatment: secondary autoimmunity is not all about B cells. Neurology. 2018;91(24):e2233–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Alcala C, Pzere-Miralles F, Gascon F, et al. Recurrent and universal alopecia areata following alemtuzumab treatment in multiple sclerosis: a secondary autoimmune disease. Mult Scler Relat Disord. 2019;27:406–8.

    PubMed  Google Scholar 

  73. Jones JL, Thompson SA, Loh P, et al. Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation. Proc Natl Acad Sci USA. 2013;110:20200–5.

    CAS  PubMed  Google Scholar 

  74. Baker D, Herrod SS, Alvarez-Gonzalez C, et al. Interpreting lymphocyte reconstitution data from the pivotal phase 3 trials of alemtuzumab. JAMA Neurol. 2017;74:961–9.

    PubMed  PubMed Central  Google Scholar 

  75. Montalban X, Hauser SL, Kappos L, et al. ORATORIO clinical investigators. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209–20.

    CAS  PubMed  Google Scholar 

  76. Conte WL, Arndt N, Cipriani VP, et al. Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol. Mult Scler Relat Disord. 2019;27:397–9.

    PubMed  Google Scholar 

  77. Cohen BA. Late-onset neutropenia following ocrelizumab therapy for multiple sclerosis. Neurology. 2019;92(9):435–6.

    PubMed  Google Scholar 

  78. Kane SV, Acquah LA. Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol. 2009;104(1):228–33.

    CAS  PubMed  Google Scholar 

  79. Simister NE. Placental transport of immunoglobulin G. Vaccine. 2003;21(24):3365–9.

    CAS  PubMed  Google Scholar 

  80. Fragoso YD, Adoni T, Brooks JBB, et al. Practical evidence-based recommendations for patients with multiple sclerosis who want to have children. Neurol Ther. 2018;7(2):207–32.

    PubMed  PubMed Central  Google Scholar 

  81. Fragoso YD. Is it correct for a woman with multiple sclerosis to forgo medication because she may become pregnant? Arq Neuropsiquiatr. 2013;71(10):826–7.

    PubMed  Google Scholar 

  82. Proschmann U, Thomas K, Thiel S, et al. Natalizumab during pregnancy and lactation. Mult Scler. 2018;24(12):1627–34.

    CAS  PubMed  Google Scholar 

  83. Baker TE, Cooper SD, Kessler L, Hale TW. Transfer of natalizumab into breast milk in a mother with multiple sclerosis. J Hum Lact. 2015;31(2):233–6.

    PubMed  Google Scholar 

  84. Arastehfar A, Wickes BL, Ilkit M, et al. Identification of mycoses in developing countries. J Fungi (Basel). 2019;5(4):E90.

    Google Scholar 

  85. Teixeira AR, Hecht MM, Guimaro MC, et al. Pathogenesis of Chagas’ disease: parasite persistence and autoimmunity. Clin Microbiol Rev. 2011;24(3):592–630.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Perez-Mazliah D, Langhorne J. CD4 T-cell subsets in malaria: TH1/TH2 revisited. Front Immunol. 2015;5:671.

    PubMed  PubMed Central  Google Scholar 

  87. Faubert G. Immune response to Giardia duodenalis. Clin Microbiol Rev. 2000;13(1):35–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Weatherhead J, Cortés AA, Sandoval C, et al. Comparison of cytokine responses in Ecuadorian children infected with Giardia, Ascaris, or both parasites. Am J Trop Med Hyg. 2017;96(6):1394–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Fragoso YD, Adoni T, Anacleto A, et al. How do we manage and treat a patient with multiple sclerosis at risk of tuberculosis? Expert Rev Neurother. 2014;14(11):1251–60.

    CAS  PubMed  Google Scholar 

  90. Mabbott NA. The influence of parasite infections on host immunity to co-infection with other pathogens. Front Immunol. 2018;9:2579.

    PubMed  PubMed Central  Google Scholar 

  91. Schramm G, Haas H. Th2 immune response against Schistosoma mansoni infection. Microbes Infect. 2010;12(12–13):881–8.

    CAS  PubMed  Google Scholar 

  92. Salazar JC, Cruz AR, Pope CD, et al. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis. 2007;195(6):879–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Alwarawrah Y, Kiernan K, MacIver NJ. Changes in nutritional status impact immune cell metabolism and function. Front Immunol. 2018;9:1055.

    PubMed  PubMed Central  Google Scholar 

  94. West-Eberhard MJ. Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity. Proc Natl Acad Sci USA. 2019;116(3):723–31.

    CAS  PubMed  Google Scholar 

  95. Calder PC. Feeding the immune system. Proc Nutr Soc. 2013;72(3):299–309.

    PubMed  Google Scholar 

  96. Gold R, Wolinsky JS, Amato MP, et al. Evolving expectations around early management of multiple sclerosis. Ther Adv Neurol Disord. 2010;3(6):351–67.

    PubMed  PubMed Central  Google Scholar 

  97. Stangel M, Penner IK, Kallmann BA, et al. Towards the implementation of ‘no evidence of disease activity’ in multiple sclerosis treatment: the multiple sclerosis decision model. Ther Adv Neurol Disord. 2015;8(1):3–13.

    PubMed  PubMed Central  Google Scholar 

  98. Hegen H, Bsteh G, Berger T. ‘No evidence of disease activity’: is it an appropriate surrogate in multiple sclerosis? Eur J Neurol. 2018;25(9):1107-e101.

    PubMed  PubMed Central  Google Scholar 

  99. Parks NE, Flanagan EP, Lucchinetti CF, et al. NEDA treatment target? No evident disease activity as an actionable outcome in practice. J Neurol Sci. 2017;383:31–4.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  101. De Giglio L, Grimaldi AE, Fubelli F, et al. Advances in preventing adverse events during monoclonal antibody management of multiple sclerosis. Expert Rev Neurother. 2019;19(5):417–29.

    PubMed  Google Scholar 

  102. Della Rosa S, Sen F. Health topics on Facebook groups: content analysis of posts in multiple sclerosis communities. Interact J Med Res. 2019;8(1):e10146.

    PubMed  PubMed Central  Google Scholar 

  103. Eijkholt M, Sparling A. Health, honesty and happiness: authenticity and anonymity in social media participation of individuals with multiple sclerosis. Mult Scler Relat Disord. 2019;27:121–6.

    PubMed  Google Scholar 

  104. Fragoso YD. Why some of us do not like the expression “no evidence of disease activity” (NEDA) in multiple sclerosis. Mult Scler Relat Disord. 2015;4(4):383–4.

    Google Scholar 

  105. Ziemssen T, Thomas K. Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world. Ther Adv Neurol Disord. 2017;10(10):343–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Carrá A, Macías Islas MA, Tarulla A, et al. Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management. Expert Rev Neurother. 2015;15(6):597–600.

    PubMed  Google Scholar 

  107. Steinberg J, Fragoso YD, Duran Quiroz JC, et al. Practical issues concerning the approval and use of biosimilar drugs for the treatment of multiple sclerosis in Latin America. Neurol Ther. 2019 (Epub 2019).

Download references

Author information

Authors and Affiliations

  1. Universidade Metropolitana de Santos, Santos, SP, Brazil

    Yara Dadalti Fragoso

  2. MS & Headache Research, Santos, SP, Brazil

    Yara Dadalti Fragoso

Authors
  1. Yara Dadalti Fragoso
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yara Dadalti Fragoso.

Ethics declarations

Funding

No private or public funding was provided for this review.

Conflict of interest

The author, Yara Dadalti Fragoso, has no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fragoso, Y.D. Adverse events and monitoring requirements associated with monoclonal antibody therapy in patients with multiple sclerosis. Drugs Ther Perspect 35, 627–634 (2019). https://doi.org/10.1007/s40267-019-00682-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40267-019-00682-0

Search

Navigation