Skip to main content

Advertisement

SpringerLink
Log in

A Clinical Approach to Existing and Emerging Therapeutics in Neuromyelitis Optica Spectrum Disorder

  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Neuromyelitis optica spectrum disorder (NMOSD) is a rare but highly disabling disease of the central nervous system. Unlike multiple sclerosis, disability in NMOSD occurs secondary to relapses that, not uncommonly, lead to blindness, paralysis, and death. Recently, newer, targeted immunotherapies have been trialed and are now in the treatment arsenal. We have endeavoured to evaluate the current state of NMOSD therapeutics.

Recent Findings

This review provides a pragmatic evaluation of recent clinical trials and post-marketing data for rituximab, inebilizumab, satralizumab, eculizumab, and ravalizumab, contrasted to older agents. We also review contemporary issues such as treatment in the context of SARS-CoV2 infection and pregnancy.

Summary

There has been a dramatic shift in NMOSD morbidity and mortality with earlier and improved disease recognition, diagnostic accuracy, and the advent of more effective, targeted therapies. Choosing a maintenance therapy remains nuanced depending on patient factors and accessibility. With over 100 putative agents in trials, disease-free survival is now a realistic goal for NMOSD patients.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Papp V, Magyari M, Aktas O, Berger T, Broadley SA, Cabre P, et al. Worldwide incidence and prevalence of neuromyelitis optica: a systematic review. Neurology. 2021;96(2):59–77. https://doi.org/10.1212/WNL.0000000000011153.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N, et al. Epidemiology of neuromyelitis optica spectrum disorder and its prevalence and incidence worldwide. Front Neurol. 2020;11:501. https://doi.org/10.3389/fneur.2020.00501.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wu Y, Zhong L, Geng J. Neuromyelitis optica spectrum disorder: pathogenesis, treatment, and experimental models. Mult Scler Relat Disord. 2019;27:412–8. https://doi.org/10.1016/j.msard.2018.12.002.

    Article  PubMed  Google Scholar 

  4. Akaishi T, Nakashima I, Takahashi T, Abe M, Ishii T, Aoki M. Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence. Neurol Neuroimmunol Neuroinflamm. 2019;7(1):e640. https://doi.org/10.1212/NXI.0000000000000640.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Songwisit S, Kosiyakul P, Jitprapaikulsan J, Prayoonwiwat N, Ungprasert P, Siritho S. Efficacy and safety of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis. Sci Rep. 2020;10(1):16727. https://doi.org/10.1038/s41598-020-73882-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12. https://doi.org/10.1016/S0140-6736(04)17551-X.

    Article  CAS  PubMed  Google Scholar 

  7. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202(4):473–7. https://doi.org/10.1084/jem.20050304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Papadopoulos MC, Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol. 2012;11(6):535–44. https://doi.org/10.1016/S1474-4422(12)70133-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hamid SHM, Whittam D, Mutch K, Linaker S, Solomon T, Das K, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088–94. https://doi.org/10.1007/s00415-017-8596-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Narayan R, Simpson A, Fritsche K, Salama S, Pardo S, Mealy M, et al. MOG antibody disease: A review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2018;25:66–72. https://doi.org/10.1016/j.msard.2018.07.025.

    Article  PubMed  Google Scholar 

  11. Tradtrantip L, Jin BJ, Yao X, Anderson MO, Verkman AS. Aquaporin-targeted therapeutics: state-of-the-field. Adv Exp Med Biol. 2017;969:239–50. https://doi.org/10.1007/978-94-024-1057-0_16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang Z, Wang KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015;38(6):364–74. https://doi.org/10.1016/j.tins.2015.04.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2008;10(1):55–66. https://doi.org/10.1007/s11940-008-0007-z.

    Article  PubMed  Google Scholar 

  14. Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010;17(8):1019–32. https://doi.org/10.1111/j.1468-1331.2010.03066.x.

    Article  CAS  PubMed  Google Scholar 

  15. Scott TF, Frohman EM, De Seze J, Gronseth GS, Weinshenker BG; Therapeutics and Technology Assessment Subcommittee of American Academy of Neurology. Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011;77(24):2128–34. https://doi.org/10.1212/WNL.0b013e31823dc535.

  16. Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206–16. https://doi.org/10.1002/ana.24554.

    Article  CAS  PubMed  Google Scholar 

  17. Qin C, Tao R, Zhang SQ, Chen B, Chen M, Yu HH, et al. Predictive factors of resistance to high-dose steroids therapy in acute attacks of neuromyelitis optica spectrum disorder. Front Neurol. 2020;11:585471. https://doi.org/10.3389/fneur.2020.585471.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Correia I, Ribeiro JJ, Isidoro L, Batista S, Nunes C, Macario C, et al. Plasma exchange in severe acute relapses of multiple sclerosis - results from a Portuguese cohort. Mult Scler Relat Disord. 2018;19:148–52. https://doi.org/10.1016/j.msard.2017.12.001.

    Article  PubMed  Google Scholar 

  19. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology. 2002;58(1):143–6. https://doi.org/10.1212/wnl.58.1.143.

    Article  CAS  PubMed  Google Scholar 

  20. Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2011;76(3):294–300. https://doi.org/10.1212/WNL.0b013e318207b1f6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Oshiro A, Nakamura S, Tamashiro K, Fujihara K. Anti-MOG + neuromyelitis optica spectrum disorders treated with plasmapheresis. No To Hattatsu. 2016;48(3):199–203.

    PubMed  Google Scholar 

  22. Song W, Qu Y, Huang X. Plasma exchange: an effective add-on treatment of optic neuritis in neuromyelitis optica spectrum disorders. Int Ophthalmol. 2019;39(11):2477–83. https://doi.org/10.1007/s10792-019-01090-z.

    Article  PubMed  Google Scholar 

  23. Aungsumart S, Apiwattanakul M. Clinical outcomes and predictive factors related to good outcomes in plasma exchange in severe attack of NMOSD and long extensive transverse myelitis: case series and review of the literature. Mult Scler Relat Disord. 2017;13:93–7. https://doi.org/10.1016/j.msard.2017.02.015.

    Article  PubMed  Google Scholar 

  24. Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Hellwig K, et al. Apheresis therapies for NMOSD attacks: a retrospective study of 207 therapeutic interventions. Neurol Neuroimmunol Neuroinflamm. 2018;5(6):e504. https://doi.org/10.1212/NXI.0000000000000504.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bonnan M, Valentino R, Debeugny S, Merle H, Ferge JL, Mehdaoui H, et al. Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 2018;89(4):346–51. https://doi.org/10.1136/jnnp-2017-316286.

    Article  PubMed  Google Scholar 

  26. Huang X, Wu J, Xiao Y, Zhang Y. Timing of plasma exchange for neuromyelitis optica spectrum disorders: a meta-analysis. Mult Scler Relat Disord. 2021;48:102709. https://doi.org/10.1016/j.msard.2020.102709.

    Article  CAS  PubMed  Google Scholar 

  27. Sergent SR, Ashurst JV. Plasmapheresis. [Updated 2022 Jul 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560566/.

  28. Espiritu AI, Pasco PMD. Efficacy and tolerability of azathioprine for neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. Mult Scler Relat Disord. 2019;33:22–32. https://doi.org/10.1016/j.msard.2019.05.011.

    Article  PubMed  Google Scholar 

  29. Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, et al. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology. 2011;77(7):659–66. https://doi.org/10.1212/WNL.0b013e31822a2780.

    Article  CAS  PubMed  Google Scholar 

  30. Poupart J, Giovannelli J, Deschamps R, Audoin B, Ciron J, Maillart E, et al. Evaluation of efficacy and tolerability of first-line therapies in NMOSD. Neurology. 2020;94(15):e1645–56. https://doi.org/10.1212/WNL.0000000000009245.

    Article  CAS  PubMed  Google Scholar 

  31. Chen H, Qiu W, Zhang Q, Wang J, Shi Z, Liu J, et al. Comparisons of the efficacy and tolerability of mycophenolate mofetil and azathioprine as treatments for neuromyelitis optica and neuromyelitis optica spectrum disorder. Eur J Neurol. 2017;24(1):219–26. https://doi.org/10.1111/ene.13186.

    Article  CAS  PubMed  Google Scholar 

  32. Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M. Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol. 2014;71(3):324–30. https://doi.org/10.1001/jamaneurol.2013.5699.

    Article  PubMed  Google Scholar 

  33. Zhang M, Zhang C, Bai P, Xue H, Wang G. Effectiveness of low dose of rituximab compared with azathioprine in Chinese patients with neuromyelitis optica: an over 2-year follow-up study. Acta Neurol Belg. 2017;117(3):695–702. https://doi.org/10.1007/s13760-017-0795-6.

    Article  PubMed  Google Scholar 

  34. Jeong IH, Park B, Kim SH, Hyun JW, Joo J, Kim HJ. Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder using multifaceted endpoints. Mult Scler. 2016;22(3):329–39. https://doi.org/10.1177/1352458515587752.

    Article  CAS  PubMed  Google Scholar 

  35. Qiu W, Kermode AG, Li R, Dai Y, Wang Y, Wang J, et al. Azathioprine plus corticosteroid treatment in Chinese patients with neuromyelitis optica. J Clin Neurosci. 2015;22(7):1178–82. https://doi.org/10.1016/j.jocn.2015.01.028.

    Article  CAS  PubMed  Google Scholar 

  36. Elsone L, Kitley J, Luppe S, Lythgoe D, Mutch K, Jacob S, et al. Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler. 2014;20(11):1533–40. https://doi.org/10.1177/1352458514525870.

    Article  CAS  PubMed  Google Scholar 

  37. Xu Y, Wang Q, Ren HT, Qiao L, Zhang Y, Fei YY, et al. Comparison of efficacy and tolerability of azathioprine, mycophenolate mofetil, and cyclophosphamide among patients with neuromyelitis optica spectrum disorder: a prospective cohort study. J Neurol Sci. 2016;370:224–8. https://doi.org/10.1016/j.jns.2016.09.035.

    Article  CAS  PubMed  Google Scholar 

  38. • Magdalena C, Clarissa A, Sutandi N. Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder treated with rituximab, azathioprine, and mycophenolate mofetil: a systematic review and meta-analysis. Innov Clin Neurosci. 2022;19(4–6):51–64. A contemporary meta-analyses comparing conventional oral immunosuppressive agents to rituximab in NMOSD.

  39. Nikoo Z, Badihian S, Shaygannejad V, Asgari N, Ashtari F. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial. J Neurol. 2017;264(9):2003–9. https://doi.org/10.1007/s00415-017-8590-0.

    Article  CAS  PubMed  Google Scholar 

  40. Yang Y, Wang CJ, Wang BJ, Zeng ZL, Guo SG. Comparison of efficacy and tolerability of azathioprine, mycophenolate mofetil, and lower dosages of rituximab among patients with neuromyelitis optica spectrum disorder. J Neurol Sci. 2018;385:192–7. https://doi.org/10.1016/j.jns.2017.12.034.

    Article  CAS  PubMed  Google Scholar 

  41. McWilliam M, Khan U. Azathioprine and the neurologist. Pract Neurol. 2020;20(1):69–74. https://doi.org/10.1136/practneurol-2018-002161.

    Article  PubMed  Google Scholar 

  42. Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, et al. Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol. 2009;66(9):1128–33. https://doi.org/10.1001/archneurol.2009.175.

    Article  PubMed  Google Scholar 

  43. Huh SY, Kim SH, Hyun JW, Joung AR, Park MS, Kim BJ, et al. Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder. JAMA Neurol. 2014;71(11):1372–8. https://doi.org/10.1001/jamaneurol.2014.2057.

    Article  PubMed  Google Scholar 

  44. Huang Q, Wang J, Zhou Y, Yang H, Wang Z, Yan Z, et al. Low-dose mycophenolate mofetil for treatment of neuromyelitis optica spectrum disorders: a prospective multicenter study in South China. Front Immunol. 2018;9:2066. https://doi.org/10.3389/fimmu.2018.02066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen H, Zhang Y, Shi Z, Feng H, Yao S, Xie J, et al. The Efficacy and tolerability of mycophenolate mofetil in treating neuromyelitis optica and neuromyelitis optica spectrum disorder in Western China. Clin Neuropharmacol. 2016;39(2):81–7. https://doi.org/10.1097/WNF.0000000000000131.

    Article  CAS  PubMed  Google Scholar 

  46. Montcuquet A, Collongues N, Papeix C, Zephir H, Audoin B, Laplaud D, et al. Effectiveness of mycophenolate mofetil as first-line therapy in AQP4-IgG, MOG-IgG, and seronegative neuromyelitis optica spectrum disorders. Mult Scler. 2017;23(10):1377–84. https://doi.org/10.1177/1352458516678474.

    Article  CAS  PubMed  Google Scholar 

  47. Wang Y, Ma J, Chang H, Zhang X, Yin L. Efficacy of mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorders: an update systematic review and meta -analysis. Mult Scler Relat Disord. 2021;55:103181. https://doi.org/10.1016/j.msard.2021.103181.

    Article  CAS  PubMed  Google Scholar 

  48. Enriquez CAG, Espiritu AI, Pasco PMD. Efficacy and tolerability of mitoxantrone for neuromyelitis optica spectrum disorder: a systematic review. J Neuroimmunol. 2019;332:126–34. https://doi.org/10.1016/j.jneuroim.2019.04.007.

    Article  CAS  PubMed  Google Scholar 

  49. Ramanathan RS, Malhotra K, Scott T. Treatment of neuromyelitis optica/neuromyelitis optica spectrum disorders with methotrexate. BMC Neurol. 2014;14:51. https://doi.org/10.1186/1471-2377-14-51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kitley J, Elsone L, George J, Waters P, Woodhall M, Vincent A, et al. Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies. J Neurol Neurosurg Psychiatry. 2013;84(8):918–21. https://doi.org/10.1136/jnnp-2012-304774.

    Article  PubMed  Google Scholar 

  51. Patti F, Lo Fermo S. Lights and shadows of cyclophosphamide in the treatment of multiple sclerosis. Autoimmune Dis. 2011;2011:961702. https://doi.org/10.4061/2011/961702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yaguchi H, Sakushima K, Takahashi I, Nishimura H, Yashima-Yamada M, Nakamura M, et al. Efficacy of intravenous cyclophosphamide therapy for neuromyelitis optica spectrum disorder. Intern Med. 2013;52(9):969–72. https://doi.org/10.2169/internalmedicine.52.7885.

    Article  CAS  PubMed  Google Scholar 

  53. Wang L, Liu K, Tan X, Zhou L, Zhang Y, Liu X, et al. Remedial effect of intravenous cyclophosphamide in corticosteroid-refractory patients in the acute phase of neuromyelitis optica spectrum disorder-related optic neuritis. Front Neurol. 2020;11:612097. https://doi.org/10.3389/fneur.2020.612097.

    Article  PubMed  Google Scholar 

  54. Whittam DH, Tallantyre EC, Jolles S, Huda S, Moots RJ, Kim HJ, et al. Rituximab in neurological disease: principles, evidence and practice. Pract Neurol. 2019;19(1):5–20. https://doi.org/10.1136/practneurol-2018-001899.

    Article  PubMed  Google Scholar 

  55. Etemadifar M, Salari M, Mirmosayyeb O, Serati M, Nikkhah R, Askari M, et al. Efficacy and safety of rituximab in neuromyelitis optica: review of evidence. J Res Med Sci. 2017;22:18. https://doi.org/10.4103/1735-1995.200275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Annovazzi P, Capobianco M, Moiola L, Patti F, Frau J, Uccelli A, et al. Rituximab in the treatment of neuromyelitis optica: a multicentre Italian observational study. J Neurol. 2016;263(9):1727–35. https://doi.org/10.1007/s00415-016-8188-y.

    Article  CAS  PubMed  Google Scholar 

  57. Damato V, Evoli A, Iorio R. Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis. JAMA Neurol. 2016;73(11):1342–8. https://doi.org/10.1001/jamaneurol.2016.1637.

    Article  PubMed  Google Scholar 

  58. Wang Y, Chang H, Zhang X, Yin L. Efficacy of rituximab in the treatment of neuromyelitis optica spectrum disorders: an update systematic review and meta -analysis. Mult Scler Relat Disord. 2021;50:102843. https://doi.org/10.1016/j.msard.2021.102843.

    Article  CAS  PubMed  Google Scholar 

  59. Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013;70(9):1110–7. https://doi.org/10.1001/jamaneurol.2013.3071.

    Article  PubMed  Google Scholar 

  60. Tahara M, Oeda T, Okada K, Ochi K, Maruyama H, Fukaura H, et al. Compassionate open-label use of rituximab following a randomised clinical trial against neuromyelitis optica (RIN-2 study): B cell monitoring-based administration. Mult Scler Relat Disord. 2022;60:103730. https://doi.org/10.1016/j.msard.2022.103730.

    Article  CAS  PubMed  Google Scholar 

  61. Tahara M, Oeda T, Okada K, Kiriyama T, Ochi K, Maruyama H, et al. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020;19(4):298–306. https://doi.org/10.1016/S1474-4422(20)30066-1.

    Article  CAS  PubMed  Google Scholar 

  62. Lindsey JW, Meulmester KM, Brod SA, Nelson F, Wolinsky JS. Variable results after rituximab in neuromyelitis optica. J Neurol Sci. 2012;317(1–2):103–5. https://doi.org/10.1016/j.jns.2012.02.017.

    Article  CAS  PubMed  Google Scholar 

  63. Perumal JS, Kister I, Howard J, Herbert J. Disease exacerbation after rituximab induction in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2015;2(1):e61. https://doi.org/10.1212/NXI.0000000000000061.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kim SH, Kim W, Li XF, Jung IJ, Kim HJ. Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol. 2011;68(11):1412–20. https://doi.org/10.1001/archneurol.2011.154.

    Article  PubMed  Google Scholar 

  65. Collongues N, Brassat D, Maillart E, Labauge P, Ouallet JC, Carra-Dalliere C, et al. Efficacy of rituximab in refractory neuromyelitis optica. Mult Scler. 2016;22(7):955–9. https://doi.org/10.1177/1352458515602337.

    Article  CAS  PubMed  Google Scholar 

  66. Zephir H, Bernard-Valnet R, Lebrun C, Outteryck O, Audoin B, Bourre B, et al. Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol. 2015;262(10):2329–35. https://doi.org/10.1007/s00415-015-7852-y.

    Article  CAS  PubMed  Google Scholar 

  67. Cabre P, Mejdoubi M, Jeannin S, Merle H, Plumelle Y, Cavillon G, et al. Treatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study. J Neurol. 2018;265(4):917–25. https://doi.org/10.1007/s00415-018-8771-5.

    Article  CAS  PubMed  Google Scholar 

  68. Pellkofer HL, Krumbholz M, Berthele A, Hemmer B, Gerdes LA, Havla J, et al. Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology. 2011;76(15):1310–5. https://doi.org/10.1212/WNL.0b013e3182152881.

    Article  CAS  PubMed  Google Scholar 

  69. Pellkofer HL, Suessmair C, Schulze A, Hohlfeld R, Kuempfel T. Course of neuromyelitis optica during inadvertent pregnancy in a patient treated with rituximab. Mult Scler. 2009;15(8):1006–8. https://doi.org/10.1177/1352458509106512.

    Article  CAS  PubMed  Google Scholar 

  70. Bedi GS, Brown AD, Delgado SR, Usmani N, Lam BL, Sheremata WA. Impact of rituximab on relapse rate and disability in neuromyelitis optica. Mult Scler. 2011;17(10):1225–30. https://doi.org/10.1177/1352458511404586.

    Article  CAS  PubMed  Google Scholar 

  71. Ip VH, Lau AY, Au LW, Fan FS, Chan AY, Mok VC, et al. Rituximab reduces attacks in Chinese patients with neuromyelitis optica spectrum disorders. J Neurol Sci. 2013;324(1–2):38–9. https://doi.org/10.1016/j.jns.2012.09.024.

    Article  CAS  PubMed  Google Scholar 

  72. Kim SH, Jeong IH, Hyun JW, Joung A, Jo HJ, Hwang SH, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica: influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol. 2015;72(9):989–95. https://doi.org/10.1001/jamaneurol.2015.1276.

    Article  PubMed  Google Scholar 

  73. Gao F, Chai B, Gu C, Wu R, Dong T, Yao Y, et al. Effectiveness of rituximab in neuromyelitis optica: a meta-analysis. BMC Neurol. 2019;19(1):36. https://doi.org/10.1186/s12883-019-1261-2.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Kunchok A, Malpas C, Nytrova P, Havrdova EK, Alroughani R, Terzi M, et al. Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2020;38:101868. https://doi.org/10.1016/j.msard.2019.101868.

    Article  PubMed  Google Scholar 

  75. Ciron J, Audoin B, Bourre B, Brassat D, Durand-Dubief F, Laplaud D, et al. Recommendations for the use of rituximab in neuromyelitis optica spectrum disorders. Rev Neurol (Paris). 2018;174(4):255–64. https://doi.org/10.1016/j.neurol.2017.11.005.

    Article  CAS  PubMed  Google Scholar 

  76. Tallantyre EC, Whittam DH, Jolles S, Paling D, Constantinesecu C, Robertson NP, et al. Secondary antibody deficiency: a complication of anti-CD20 therapy for neuroinflammation. J Neurol. 2018;265(5):1115–22. https://doi.org/10.1007/s00415-018-8812-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108(9):3701–6. https://doi.org/10.1073/pnas.1017385108.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Chen D, Gallagher S, Monson NL, Herbst R, Wang Y. Inebilizumab, a B cell-depleting anti-CD19 antibody for the treatment of autoimmune neurological diseases: insights from preclinical studies. J Clin Med. 2016;5(12):107. https://doi.org/10.3390/jcm5120107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, et al. B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010;335(1):213–22. https://doi.org/10.1124/jpet.110.168062.

    Article  CAS  PubMed  Google Scholar 

  80. Ward E, Mittereder N, Kuta E, Sims GP, Bowen MA, Dall’Acqua W, et al. A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo. Br J Haematol. 2011;155(4):426–37. https://doi.org/10.1111/j.1365-2141.2011.08857.x.

    Article  CAS  PubMed  Google Scholar 

  81. Gallagher S, Turman S, Yusuf I, Akhgar A, Wu Y, Roskos LK, et al. Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice. Int Immunopharmacol. 2016;36:205–12. https://doi.org/10.1016/j.intimp.2016.04.035.

    Article  CAS  PubMed  Google Scholar 

  82. Gallagher S, Yusuf I, McCaughtry TM, Turman S, Sun H, Kolbeck R, et al. MEDI-551 treatment effectively depletes B cells and reduces serum titers of autoantibodies in mice transgenic for Sle1 and human CD19. Arthritis Rheumatol. 2016;68(4):965–76. https://doi.org/10.1002/art.39503.

    Article  CAS  PubMed  Google Scholar 

  83. Frampton JE. Inebilizumab: first approval. Drugs. 2020;80(12):1259–64. https://doi.org/10.1007/s40265-020-01370-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Yan L, Wang B, She D, Mitchell B, Criste R, Cimbora D, et al. Pharmacodynamic modelling and exposure-response assessment of inebilizumab in subjects with neuromyelitis optica spectrum disorders. Br J Clin Pharmacol. 2022;88(8):3803–12. https://doi.org/10.1111/bcp.15332.

    Article  CAS  PubMed  Google Scholar 

  85. •• Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352–63. https://doi.org/10.1016/S0140-6736(19)31817-3. Phase III randomized controlled trial of inebilizumab in NMOSD compared to placebo, stopped early due to reaching efficacy stopping rules. Truly placebo-controlled, widely recruited trial with, intended treatment phase period of only 6 months to avoid protracted risk of relapse.

    Article  CAS  PubMed  Google Scholar 

  86. Rensel M, Zabeti A, Mealy MA, Cimbora D, She D, Drappa J, et al. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for ⩾4 years in the N-MOmentum trial. Mult Scler. 2022;28(6):925–32. https://doi.org/10.1177/13524585211047223.

    Article  CAS  PubMed  Google Scholar 

  87. Marignier R, Pittock SJ, Paul F, Kim HJ, Bennett JL, Weinshenker BG, et al. AQP4-IgG-seronegative patient outcomes in the N-MOmentum trial of inebilizumab in neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2022;57:103356. https://doi.org/10.1016/j.msard.2021.103356.

    Article  CAS  PubMed  Google Scholar 

  88. Marignier R, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk D, et al. Disability outcomes in the N-MOmentum trial of inebilizumab in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2021;8(3):e978. https://doi.org/10.1212/NXI.0000000000000978.

  89. Bennett JL, Aktas O, Rees WA, Smith MA, Gunsior M, Yan L, et al. Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: an exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial. EBioMedicine. 2022;86:104321. https://doi.org/10.1016/j.ebiom.2022.104321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Flanagan EP, Levy M, Katz E, Cimbora D, Drappa J, Mealy MA, et al. Inebilizumab for treatment of neuromyelitis optica spectrum disorder in patients with prior rituximab use from the N-MOmentum Study. Mult Scler Relat Disord. 2022;57:103352. https://doi.org/10.1016/j.msard.2021.103352.

    Article  CAS  PubMed  Google Scholar 

  91. Fujihara K, Bennett JL, de Seze J, Haramura M, Kleiter I, Weinshenker BG, et al. Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e841. https://doi.org/10.1212/NXI.0000000000000841.

  92. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010;40(7):1830–5. https://doi.org/10.1002/eji.201040391.

    Article  CAS  PubMed  Google Scholar 

  93. Lin J, Li X, Xia J. Th17 cells in neuromyelitis optica spectrum disorder: a review. Int J Neurosci. 2016;126(12):1051–60. https://doi.org/10.3109/00207454.2016.1163550.

    Article  CAS  PubMed  Google Scholar 

  94. Takeshita Y, Obermeier B, Cotleur AC, Spampinato SF, Shimizu F, Yamamoto E, et al. Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm. 2017;4(1):e311. https://doi.org/10.1212/NXI.0000000000000311.

    Article  PubMed  Google Scholar 

  95. Takeshita Y, Fujikawa S, Serizawa K, Fujisawa M, Matsuo K, Nemoto J, et al. New BBB model reveals that IL-6 blockade suppressed the BBB disorder, preventing onset of NMOSD. Neurol Neuroimmunol Neuroinflamm. 2021;8(6):e1076. https://doi.org/10.1212/NXI.0000000000001076.

  96. Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci. 2012;8(9):1254–66. https://doi.org/10.7150/ijbs.4679.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Vallejo R, Tilley DM, Vogel L, Benyamin R. The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract. 2010;10(3):167–84. https://doi.org/10.1111/j.1533-2500.2010.00367.x.

    Article  PubMed  Google Scholar 

  98. Arruda JL, Sweitzer S, Rutkowski MD, DeLeo JA. Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Res. 2000;879(1–2):216–25. https://doi.org/10.1016/s0006-8993(00)02807-9.

    Article  CAS  PubMed  Google Scholar 

  99. Serizawa K, Tomizawa-Shinohara H, Yasuno H, Yogo K, Matsumoto Y. Anti-IL-6 receptor antibody inhibits spontaneous pain at the pre-onset of experimental autoimmune encephalomyelitis in mice. Front Neurol. 2019;10:341. https://doi.org/10.3389/fneur.2019.00341.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Uzawa A, Mori M, Arai K, Sato Y, Hayakawa S, Masuda S, et al. Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. Mult Scler. 2010;16(12):1443–52. https://doi.org/10.1177/1352458510379247.

    Article  CAS  PubMed  Google Scholar 

  101. Barros PO, Cassano T, Hygino J, Ferreira TB, Centuriao N, Kasahara TM, et al. Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase. Clin Exp Immunol. 2016;183(3):480–9. https://doi.org/10.1111/cei.12733.

    Article  CAS  PubMed  Google Scholar 

  102. Matsushita T, Tateishi T, Isobe N, Yonekawa T, Yamasaki R, Matsuse D, et al. Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis. PLoS One. 2013;8(4):e61835. https://doi.org/10.1371/journal.pone.0061835.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Icoz S, Tuzun E, Kurtuncu M, Durmus H, Mutlu M, Eraksoy M, et al. Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients. Int J Neurosci. 2010;120(1):71–5. https://doi.org/10.3109/00207450903428970.

    Article  PubMed  Google Scholar 

  104. Wei Y, Chang H, Li X, Wang H, Du L, Zhou H, et al. Cytokines and tissue damage biomarkers in first-onset neuromyelitis optica spectrum disorders: significance of interleukin-6. NeuroImmunoModulation. 2018;25(4):215–24. https://doi.org/10.1159/000494976.

    Article  CAS  PubMed  Google Scholar 

  105. Uzawa A, Mori M, Masuda H, Ohtani R, Uchida T, Sawai S, et al. Interleukin-6 analysis of 572 consecutive CSF samples from neurological disorders: a special focus on neuromyelitis optica. Clin Chim Acta. 2017;469:144–9. https://doi.org/10.1016/j.cca.2017.03.006.

    Article  CAS  PubMed  Google Scholar 

  106. Uzawa A, Mori M, Sawai S, Masuda S, Muto M, Uchida T, et al. Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks. Clin Chim Acta. 2013;421:181–3. https://doi.org/10.1016/j.cca.2013.03.020.

    Article  CAS  PubMed  Google Scholar 

  107. Uzawa A, Mori M, Ito M, Uchida T, Hayakawa S, Masuda S, et al. Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis. J Neurol. 2009;256(12):2082–4. https://doi.org/10.1007/s00415-009-5274-4.

    Article  CAS  PubMed  Google Scholar 

  108. Wang H, Wang K, Zhong X, Dai Y, Qiu W, Wu A, et al. Notable increased cerebrospinal fluid levels of soluble interleukin-6 receptors in neuromyelitis optica. NeuroImmunoModulation. 2012;19(5):304–8. https://doi.org/10.1159/000339302.

    Article  CAS  PubMed  Google Scholar 

  109. •• Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114–24. https://doi.org/10.1056/NEJMoa1901747. Phase III randomized placebo-controlled trial of satralizumab add on to immunosuppressive therapy in NMOSD.

  110. Igawa T, Ishii S, Tachibana T, Maeda A, Higuchi Y, Shimaoka S, et al. Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization. Nat Biotechnol. 2010;28(11):1203–7. https://doi.org/10.1038/nbt.1691.

    Article  CAS  PubMed  Google Scholar 

  111. •• Traboulsee A, Greenberg BM, Bennett JL, Szczechowski L, Fox E, Shkrobot S, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402–12. https://doi.org/10.1016/S1474-4422(20)30078-8. Phase III randomized placebo-controlled trial of satralizumab immunosuppressive therapy in NMOSD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Kleiter I, Traboulsee A, Palace J, Yamamura T, Fujihara K, Saiz A, et al. Long-term efficacy of satralizumab in AQP4-IgG-seropositive neuromyelitis optica spectrum disorder from SAkuraSky and SAkuraStar. Neurol Neuroimmunol Neuroinflamm. 2022;10(1):e200071. https://doi.org/10.1212/NXI.0000000000200071.

  113. Duchow A, Bellmann-Strobl J. Satralizumab in the treatment of neuromyelitis optica spectrum disorder. Neurodegener Dis Manag. 2021;11(1):49–59. https://doi.org/10.2217/nmt-2020-0046.

    Article  PubMed  Google Scholar 

  114. Lotan I, McGowan R, Levy M. Anti-IL-6 therapies for neuromyelitis optica spectrum disorders: a systematic review of safety and efficacy. Curr Neuropharmacol. 2021;19(2):220–32. https://doi.org/10.2174/1570159X18666200429010825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Yamamura T, Weinshenker B, Yeaman MR, De Seze J, Patti F, Lobo P, et al. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022;66:104025. https://doi.org/10.1016/j.msard.2022.104025.

    Article  CAS  PubMed  Google Scholar 

  116. Hoffmann-La Roche Limited. https://www.rochecanada.com/PMs/Actemra/Actemra_PM_E.pdf. Date of initial authorization 30 Apr 2010 [Amended 20 June 2023]. Accessed 19 March 2023.

  117. Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T. Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol. 2013;23(4):827–31. https://doi.org/10.1007/s10165-012-0715-9.

    Article  CAS  PubMed  Google Scholar 

  118. Kieseier BC, Stuve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, et al. Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses. JAMA Neurol. 2013;70(3):390–3. https://doi.org/10.1001/jamaneurol.2013.668.

    Article  PubMed  Google Scholar 

  119. Lauenstein AS, Stettner M, Kieseier BC, Lensch E. Treating neuromyelitis optica with the interleukin-6 receptor antagonist tocilizumab. BMJ Case Rep. 2014;2014:bcr2013202939. https://doi.org/10.1136/bcr-2013-202939.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Harmel J, Ringelstein M, Ingwersen J, Mathys C, Goebels N, Hartung HP, et al. Interferon-beta-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab. BMC Neurol. 2014;14:247. https://doi.org/10.1186/s12883-014-0247-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Breu M, Glatter S, Hoftberger R, Freilinger M, Kircher K, Kasprian G, et al. Two cases of pediatric AQP4-antibody positive neuromyelitis optica spectrum disorder successfully treated with tocilizumab. Neuropediatrics. 2019;50(3):193–6. https://doi.org/10.1055/s-0039-1684004.

    Article  PubMed  Google Scholar 

  122. Komai T, Shoda H, Yamaguchi K, Sakurai K, Shibuya M, Kubo K, et al. Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: a case report. Mod Rheumatol. 2016;26(2):294–6. https://doi.org/10.3109/14397595.2013.861333.

    Article  PubMed  Google Scholar 

  123. Marino A, Narula S, Lerman MA. First Pediatric patient with neuromyelitis optica and sjogren syndrome successfully treated with tocilizumab. Pediatr Neurol. 2017;73:e5–6. https://doi.org/10.1016/j.pediatrneurol.2017.05.015.

    Article  PubMed  Google Scholar 

  124. Ayzenberg I, Kleiter I, Schroder A, Hellwig K, Chan A, Yamamura T, et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol. 2013;70(3):394–7. https://doi.org/10.1001/jamaneurol.2013.1246.

    Article  PubMed  Google Scholar 

  125. Carreon Guarnizo E, Hernandez Clares R, Castillo Trivino T, Meca Lallana V, Arocas Casan V, Iniesta Martinez F, et al. Experience with tocilizumab in patients with neuromyelitis optica spectrum disorders. Neurologia (Engl Ed). 2022;37(3):178–83. https://doi.org/10.1016/j.nrleng.2018.12.021.

    Article  CAS  PubMed  Google Scholar 

  126. Ringelstein M, Ayzenberg I, Harmel J, Lauenstein AS, Lensch E, Stogbauer F, et al. Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol. 2015;72(7):756–63. https://doi.org/10.1001/jamaneurol.2015.0533.

    Article  PubMed  Google Scholar 

  127. Araki M, Matsuoka T, Miyamoto K, Kusunoki S, Okamoto T, Murata M, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology. 2014;82(15):1302–6. https://doi.org/10.1212/WNL.0000000000000317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Rigal J, Pugnet G, Ciron J, Lepine Z, Biotti D. Off-label use of tocilizumab in neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases: a case-series. Mult Scler Relat Disord. 2020;46:102483. https://doi.org/10.1016/j.msard.2020.102483.

    Article  CAS  PubMed  Google Scholar 

  129. Lotan I, Charlson RW, Ryerson LZ, Levy M, Kister I. Effectiveness of subcutaneous tocilizumab in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord. 2019;39:101920. https://doi.org/10.1016/j.msard.2019.101920.

    Article  PubMed  Google Scholar 

  130. Du C, Zeng P, Han JR, Zhang TX, Jia D, Shi FD, et al. Early initiation of tocilizumab treatment against moderate-to-severe myelitis in neuromyelitis optica spectrum disorder. Front Immunol. 2021;12:660230. https://doi.org/10.3389/fimmu.2021.660230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Xie Q, Zheng T, Sun M, Sun J, Wang M. A meta-analysis to determine the efficacy and safety of tocilizumab in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord. 2020;45:102421. https://doi.org/10.1016/j.msard.2020.102421.

    Article  PubMed  Google Scholar 

  132. Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, et al. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020;19(5):391–401. https://doi.org/10.1016/S1474-4422(20)30070-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Stathopoulos P, Dalakas MC. The role of complement and complement therapeutics in neuromyelitis optica spectrum disorders. Expert Rev Clin Immunol. 2022;18(9):933–45. https://doi.org/10.1080/1744666X.2022.2105205.

    Article  CAS  PubMed  Google Scholar 

  134. Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain. 2002;125(Pt 7):1450–61. https://doi.org/10.1093/brain/awf151.

    Article  PubMed  Google Scholar 

  135. Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP, Kryzer TJ, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007;69(24):2221–31. https://doi.org/10.1212/01.WNL.0000289761.64862.ce.

    Article  CAS  PubMed  Google Scholar 

  136. Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50. https://doi.org/10.1073/pnas.1109980108.

    Article  PubMed  Google Scholar 

  137. Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133(Pt 2):349–61. https://doi.org/10.1093/brain/awp309.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Duan T, Smith AJ, Verkman AS. Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflammation. 2018;15(1):294. https://doi.org/10.1186/s12974-018-1333-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. •• Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614–25. https://doi.org/10.1056/NEJMoa1900866. Phase III randomized controlled trial of eculizumab in NMOSD compared to placebo.

    Article  CAS  PubMed  Google Scholar 

  140. Singh P, Gao X, Kleijn HJ, Bellanti F, Pelto R. Eculizumab pharmacokinetics and pharmacodynamics in patients with neuromyelitis optica spectrum disorder. Front Neurol. 2021;12:696387. https://doi.org/10.3389/fneur.2021.696387.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Wingerchuk DM, Fujihara K, Palace J, Berthele A, Levy M, Kim HJ, et al. Long-term safety and efficacy of eculizumab in aquaporin-4 IgG-positive NMOSD. Ann Neurol. 2021;89(6):1088–98. https://doi.org/10.1002/ana.26049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Palace J, Wingerchuk DM, Fujihara K, Berthele A, Oreja-Guevara C, Kim HJ, et al. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: subgroup analyses of the randomized controlled phase 3 PREVENT trial. Mult Scler Relat Disord. 2021;47:102641. https://doi.org/10.1016/j.msard.2020.102641.

    Article  CAS  PubMed  Google Scholar 

  143. Pittock SJ, Fujihara K, Palace J, Berthele A, Kim HJ, Oreja-Guevara C, et al. Eculizumab monotherapy for NMOSD: data from PREVENT and its open-label extension. Mult Scler. 2022;28(3):480–6. https://doi.org/10.1177/13524585211038291.

    Article  CAS  PubMed  Google Scholar 

  144. Kim HJ, Nakashima I, Viswanathan S, Wang KC, Shang S, Miller L, et al. Eculizumab in Asian patients with anti-aquaporin-IgG-positive neuromyelitis optica spectrum disorder: a subgroup analysis from the randomized phase 3 PREVENT trial and its open-label extension. Mult Scler Relat Disord. 2021;50:102849. https://doi.org/10.1016/j.msard.2021.102849.

    Article  CAS  PubMed  Google Scholar 

  145. Chatterton S, Parratt JDE, Ng K. Eculizumab for acute relapse of neuromyelitis optica spectrum disorder: case report. Front Neurol. 2022;13:951423. https://doi.org/10.3389/fneur.2022.951423.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Digala L, Katyal N, Narula N, Govindarajan R. Eculizumab in the treatment of aquaporin-4 seronegative neuromyelitis optica spectrum disorder: a case report. Front Neurol. 2021;12:660741. https://doi.org/10.3389/fneur.2021.660741.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Saab G, Munoz DG, Rotstein DL. Chronic cognitive impairment in AQP4+ NMOSD with improvement in cognition on eculizumab: a report of two cases. Front Neurol. 2022;13:863151. https://doi.org/10.3389/fneur.2022.863151.

    Article  PubMed  PubMed Central  Google Scholar 

  148. •• Wingerchuk DM, Zhang I, Kielhorn A, Royston M, Levy M, Fujihara K, et al. Network meta-analysis of food and drug administration-approved treatment options for adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder. Neurol Ther. 2022;11(1):123–35. https://doi.org/10.1007/s40120-021-00295-8. An elegant meta-analysis with the goal of comparing current pivotal trials in NMOSD to distinguish treatment response between them within limits of such an analysis.

    Article  PubMed  Google Scholar 

  149. Shi M, Chu F, Jin T, Zhu J. Progress in treatment of neuromyelitis optica spectrum disorders (NMOSD): novel insights into therapeutic possibilities in NMOSD. CNS Neurosci Ther. 2022;28(7):981–91. https://doi.org/10.1111/cns.13836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. McNamara LA, Topaz N, Wang X, Hariri S, Fox L, MacNeil JR. High risk for invasive meningococcal disease among patients receiving eculizumab (Soliris) despite receipt of meningococcal vaccine. MMWR Morb Mortal Wkly Rep. 2017;66(27):734–7. https://doi.org/10.15585/mmwr.mm6627e1.

    Article  PubMed  PubMed Central  Google Scholar 

  151. •• Pittock SJ, Barnett M, Bennett JL, Berthele A, de Sèze J, Levy M, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1053–68. https://doi.org/10.1002/ana.26626. Randomized controlled trial of ravulizumab in NMOSD compared to placebo. PREVENT trial placebo group used as historial controls, with NO relapses in the treatment group seen during the trial.

    Article  CAS  PubMed  Google Scholar 

  152. Dalakas MC. Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis. Expert Rev Clin Immunol. 2022;18(7):691–701. https://doi.org/10.1080/1744666X.2022.2082946.

    Article  CAS  PubMed  Google Scholar 

  153. Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540–9. https://doi.org/10.1182/blood-2018-09-876805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Fureder W, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133(6):530–9. https://doi.org/10.1182/blood-2018-09-876136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol. 2021;20(1):60–7. https://doi.org/10.1016/S1474-4422(20)30392-6.

    Article  CAS  PubMed  Google Scholar 

  156. Shimizu Y, Fujihara K, Ohashi T, Nakashima I, Yokoyama K, Ikeguch R, et al. Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder. Mult Scler. 2016;22(11):1413–20. https://doi.org/10.1177/1352458515583376.

    Article  PubMed  Google Scholar 

  157. Costello F, Burton JM. Contemporary management challenges in seropositive NMOSD. J Neurol. 2022;269(10):5674–81. https://doi.org/10.1007/s00415-022-11241-5.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Collongues N, Alves Do Rego C, Bourre B, Biotti D, Marignier R, da Silva AM, et al. Pregnancy in patients with AQP4-Ab, MOG-Ab, or double-negative neuromyelitis optica disorder. Neurology. 2021;96(15):e2006–15. https://doi.org/10.1212/WNL.0000000000011744.

    Article  CAS  PubMed  Google Scholar 

  159. Belizna C, Meroni PL, Shoenfeld Y, Devreese K, Alijotas-Reig J, Esteve-Valverde E, et al. In utero exposure to azathioprine in autoimmune disease. Where do we stand? Autoimmun Rev. 2020;19(9):102525. https://doi.org/10.1016/j.autrev.2020.102525.

    Article  CAS  PubMed  Google Scholar 

  160. Hyoun SC, Obican SG, Scialli AR. Teratogen update: methotrexate. Birth Defects Res A Clin Mol Teratol. 2012;94(4):187–207. https://doi.org/10.1002/bdra.23003.

    Article  CAS  PubMed  Google Scholar 

  161. Asgari N, Henriksen TB, Petersen T, Lillevang ST, Weinshenker BG. Pregnancy outcomes in a woman with neuromyelitis optica. Neurology. 2014;83(17):1576–7. https://doi.org/10.1212/WNL.0000000000000911.

    Article  PubMed  Google Scholar 

  162. Coscia LA, Armenti DP, King RW, Sifontis NM, Constantinescu S, Moritz MJ. Update on the teratogenicity of maternal mycophenolate mofetil. J Pediatr Genet. 2015;4(2):42–55. https://doi.org/10.1055/s-0035-1556743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Krysko KM, Bove R, Dobson R, Jokubaitis V, Hellwig K. Treatment of women with multiple sclerosis planning pregnancy. Curr Treat Options Neurol. 2021;23(4):11. https://doi.org/10.1007/s11940-021-00666-4.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Smith JB, Hellwig K, Fink K, Lyell DJ, Piehl F, Langer-Gould A. Rituximab, MS, and pregnancy. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e734. https://doi.org/10.1212/NXI.0000000000000734.

    Article  PubMed  PubMed Central  Google Scholar 

  165. Database DaL: Rituximab https://www.ncbi.nlm.nih.gov/books/NBK501798/ (2023). Accessed April 4 2023

  166. Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011;117(5):1499–506. https://doi.org/10.1182/blood-2010-07-295444.

    Article  CAS  PubMed  Google Scholar 

  167. Klink DT, van Elburg RM, Schreurs MW, van Well GT. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol. 2008;2008:271363. https://doi.org/10.1155/2008/271363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Morales E, Galindo A, Garcia L, Villalain C, Alonso M, Gutierrez E, et al. Eculizumab in early-stage pregnancy. Kidney Int Rep. 2020;5(12):2383–7. https://doi.org/10.1016/j.ekir.2020.09.045.

    Article  PubMed  PubMed Central  Google Scholar 

  169. Sarno L, Tufano A, Maruotti GM, Martinelli P, Balletta MM, Russo D. Eculizumab in pregnancy: a narrative overview. J Nephrol. 2019;32(1):17–25. https://doi.org/10.1007/s40620-018-0517-z.

    Article  CAS  PubMed  Google Scholar 

  170. Soliris product monograph. https://alexion.com/Documents/Canada/Product-Monograph-Soliris-English-20Aug2018.aspx Accessed March 19 2023.

  171. •• Newsome SD, Cross AH, Fox RJ, Halper J, Kanellis P, Bebo B, et al. COVID-19 in patients with neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody disease in North America: from the COViMS Registry. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1057. https://doi.org/10.1212/NXI.0000000000001057. A study on risk factors in the setting of COVID-19 and their relation to NMOSD.

  172. Sormani MP, De Rossi N, Schiavetti I, Carmisciano L, Cordioli C, Moiola L, et al. Disease-modifying therapies and coronavirus disease 2019 severity in multiple sclerosis. Ann Neurol. 2021;89(4):780–9. https://doi.org/10.1002/ana.26028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Giovannoni G. Anti-CD20 immunosuppressive disease-modifying therapies and COVID-19. Mult Scler Relat Disord. 2020;41:102135. https://doi.org/10.1016/j.msard.2020.102135.

    Article  PubMed  PubMed Central  Google Scholar 

  174. Salter A, Fox RJ, Newsome SD, Halper J, Li DKB, Kanellis P, et al. Outcomes and risk factors associated with SARS-CoV-2 infection in a North American Registry of patients with multiple sclerosis. JAMA Neurol. 2021;78(6):699–708. https://doi.org/10.1001/jamaneurol.2021.0688.

    Article  PubMed  Google Scholar 

  175. Abboud H, Zheng C, Kar I, Chen CK, Sau C, Serra A. Current and emerging therapeutics for neuromyelitis optica spectrum disorder: relevance to the COVID-19 pandemic. Mult Scler Relat Disord. 2020;44:102249. https://doi.org/10.1016/j.msard.2020.102249.

    Article  PubMed  PubMed Central  Google Scholar 

  176. Khiali S, Khani E, Entezari-Maleki T. A comprehensive review of tocilizumab in COVID-19 acute respiratory distress syndrome. J Clin Pharmacol. 2020;60(9):1131–46. https://doi.org/10.1002/jcph.1693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5):e01753–18. https://doi.org/10.1128/mBio.01753-18.

  178. Ruggenenti P, Di Marco F, Cortinovis M, Lorini L, Sala S, Novelli L, et al. Eculizumab in patients with severe coronavirus disease 2019 (COVID-19) requiring continuous positive airway pressure ventilator support: retrospective cohort study. PLoS One. 2021;16(12):e0261113. https://doi.org/10.1371/journal.pone.0261113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. van Kempen ZLE, Wieske L, Stalman EW, Kummer LYL, van Dam PJ, Volkers AG, et al. Longitudinal humoral response after SARS-CoV-2 vaccination in ocrelizumab treated MS patients: to wait and repopulate? Mult Scler Relat Disord. 2022;57:103416. https://doi.org/10.1016/j.msard.2021.103416.

    Article  CAS  PubMed  Google Scholar 

  180. Boekel L, Steenhuis M, Hooijberg F, Besten YR, van Kempen ZLE, Kummer LY, et al. Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies. Lancet Rheumatol. 2021;3(11):e778–88. https://doi.org/10.1016/S2665-9913(21)00222-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Kroger A, Bahta L, Long S, Sanchez P. General best practice guidelines for immunization. www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Accessed 15 Apr 2023.

  182. Hoffmann-La Roche Limited. https://pdf.hres.ca/dpd_pm/00056524.PDF. Date of initial approval 1 June 2020. Accessed 19 Mar 2023.

  183. Alexion Pharma GmbH. https://alexion.com/documents/ultomiris_product_monograph_approved_english. Date of initial authorization 28 Aug 2019 [Amended 6 Jan 2023]. Accessed 19 Mar 2023.

  184. Yang Y, Chen L, Wu L, Yao J, Wang N, Su X, et al. Effective rituximab treatment in patients with neuromyelitis optica spectrum disorders compared with azathioprine and mycophenolate. Neurol Ther. 2022;11(1):137–49. https://doi.org/10.1007/s40120-021-00298-5.

    Article  PubMed  Google Scholar 

  185. Brod SA. Review of approved NMO therapies based on mechanism of action, efficacy and long-term effects. Mult Scler Relat Disord. 2020;46:102538. https://doi.org/10.1016/j.msard.2020.102538.

    Article  PubMed  PubMed Central  Google Scholar 

  186. Burt RK, Balabanov R, Han X, Burns C, Gastala J, Jovanovic B, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation for neuromyelitis optica. Neurology. 2019;93(18):e1732–41. https://doi.org/10.1212/WNL.0000000000008394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Burton JM, Duggan P, Costello F, Metz L, Storek J. A pilot trial of autologous hematopoietic stem cell transplant in neuromyelitis optic spectrum disorder. Mult Scler Relat Disord. 2021;53:102990. https://doi.org/10.1016/j.msard.2021.102990.

    Article  PubMed  Google Scholar 

  188. • Greco R, Bondanza A, Oliveira MC, Badoglio M, Burman J, Piehl F, et al. Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT Autoimmune Diseases Working Party. Mult Scler. 2015;21(2):189–97. https://doi.org/10.1177/1352458514541978. An elegant summary of case series and learning points from initial efforts to trial bone marrow transplantation in NMOSD.

    Article  PubMed  Google Scholar 

  189. Hoay KY, Ratnagopal P. Autologous hematopoietic stem cell transplantation for the treatment of neuromyelitis optica in Singapore. Acta Neurol Taiwan. 2018;27(1):26–32.

    PubMed  Google Scholar 

  190. Zhang P, Liu B. Effect of autologous hematopoietic stem cell transplantation on multiple sclerosis and neuromyelitis optica spectrum disorder: a PRISMA-compliant meta-analysis. Bone Marrow Transplant. 2020;55(10):1928–34. https://doi.org/10.1038/s41409-020-0810-z.

    Article  PubMed  Google Scholar 

  191. Nabizadeh F, Masrouri S, Sharifkazemi H, Azami M, Nikfarjam M, Moghadasi AN. Autologous hematopoietic stem cell transplantation in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. J Clin Neurosci. 2022;105:37–44. https://doi.org/10.1016/j.jocn.2022.08.020.

    Article  CAS  PubMed  Google Scholar 

  192. Khan TR, Zimmern V, Aquino V, Wang C. Autologous hematopoietic stem cell transplantation in a pediatric patient with aquaporin-4 neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2021;50:102852. https://doi.org/10.1016/j.msard.2021.102852.

    Article  CAS  PubMed  Google Scholar 

  193. Matiello M, Pittock SJ, Porrata L, Weinshenker BG. Failure of autologous hematopoietic stem cell transplantation to prevent relapse of neuromyelitis optica. Arch Neurol. 2011;68(7):953–5. https://doi.org/10.1001/archneurol.2011.38.

    Article  PubMed  Google Scholar 

  194. Peng F, Qiu W, Li J, Hu X, Huang R, Lin D, et al. A preliminary result of treatment of neuromyelitis optica with autologous peripheral hematopoietic stem cell transplantation. Neurologist. 2010;16(6):375–8. https://doi.org/10.1097/NRL.0b013e3181b126e3.

    Article  PubMed  Google Scholar 

  195. Fu Y, Yan Y, Qi Y, Yang L, Li T, Zhang N, et al. Impact of autologous mesenchymal stem cell infusion on neuromyelitis optica spectrum disorder: a pilot, 2-year observational study. CNS Neurosci Ther. 2016;22(8):677–85. https://doi.org/10.1111/cns.12559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Ceglie G, Papetti L, Valeriani M, Merli P. Hematopoietic stem cell transplantation in Neuromyelitis Optica-Spectrum Disorders (NMO-SD): state-of-the-art and future perspectives. Int J Mol Sci. 2020;21(15):5304. https://doi.org/10.3390/ijms21155304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Le Garff-Tavernier M, Herbi L, de Romeuf C, Nguyen-Khac F, Davi F, Grelier A, et al. Antibody-dependent cellular cytotoxicity of the optimized anti-CD20 monoclonal antibody ublituximab on chronic lymphocytic leukemia cells with the 17p deletion. Leukemia. 2014;28(1):230–3. https://doi.org/10.1038/leu.2013.240.

    Article  CAS  PubMed  Google Scholar 

  198. Steinman L, Fox E, Hartung HP, Alvarez E, Qian P, Wray S, et al. Ublituximab versus teriflunomide in relapsing multiple sclerosis. N Engl J Med. 2022;387(8):704–14. https://doi.org/10.1056/NEJMoa2201904.

    Article  CAS  PubMed  Google Scholar 

  199. Mealy MA, Levy M. A pilot safety study of ublituximab, a monoclonal antibody against CD20, in acute relapses of neuromyelitis optica spectrum disorder. Medicine (Baltimore). 2019;98(25):e15944. https://doi.org/10.1097/MD.0000000000015944.

    Article  PubMed  Google Scholar 

  200. Zhang C, Tian DC, Yang CS, Han B, Wang J, Yang L, et al. Safety and efficacy of bortezomib in patients with highly relapsing neuromyelitis optica spectrum disorder. JAMA Neurol. 2017;74(8):1010–2. https://doi.org/10.1001/jamaneurol.2017.1336.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Pancheri E, Guglielmi V, Wilczynski GM, Malatesta M, Tonin P, Tomelleri G, et al. Non-hematologic toxicity of bortezomib in multiple myeloma: the neuromuscular and cardiovascular adverse effects. Cancers (Basel). 2020;12(9):2540. https://doi.org/10.3390/cancers12092540.

  202. Katz Sand I, Fabian MT, Telford R, Kraus TA, Chehade M, Masilamani M, et al. Open-label, add-on trial of cetirizine for neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2018;5(2):e441. https://doi.org/10.1212/NXI.0000000000000441.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Levy M, Mealy MA. Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2014;1(1):e5. https://doi.org/10.1212/NXI.0000000000000005.

    Article  PubMed  PubMed Central  Google Scholar 

  204. Kim W, Kim SH, Kim HJ. New insights into neuromyelitis optica. J Clin Neurol. 2011;7(3):115–27. https://doi.org/10.3988/jcn.2011.7.3.115.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Funding for figure reproduction was provided by an unrestricted research grant from the University of Calgary, Calgary, Alberta.

Author information

Authors and Affiliations

  1. Division of Neurology, Department of Clinical Neurosciences, University of Calgary, Cummings School of Medicine, Calgary, AB, Canada

    Heather Y. F. Yong & Jodie M. Burton

  2. Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada

    Jodie M. Burton

  3. Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada

    Jodie M. Burton

Authors
  1. Heather Y. F. Yong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jodie M. Burton
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.Y. performed the literature review with support from J.M.B. H.Y. drafted all figures and tables. Both authors contributed to manuscript content and final review.

Corresponding author

Correspondence to Jodie M. Burton.

Ethics declarations

Conflict of Interest

H.Y. has nothing to disclose. J.M.B. has received honoraria for consulting and speaking engagements from Roche, Alexion, Novartis, and Biogen.

Human and Animal Rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

Disclaimer

The corresponding author J.M.B. takes full responsibility for the data, the analyses and interpretation, and the conduct of the research. The principal author had full access to all of the data and has the right to publish any and all data separate and apart from any sponsor.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yong, H.Y.F., Burton, J.M. A Clinical Approach to Existing and Emerging Therapeutics in Neuromyelitis Optica Spectrum Disorder. Curr Neurol Neurosci Rep 23, 489–506 (2023). https://doi.org/10.1007/s11910-023-01287-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-023-01287-x

Keywords

Search

Navigation