Progress of neuromyelitis optica spectrum disorder treatment_West China Medical Journal

Authors：

LIANG Chen ,  LU Fang

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LU Fang, Email: lufang@wschscu.cn

Keywords：

Neuromyelitis optica spectrum disorder; aquaporin-4; monoclonal antibody

DOI：

10.7507/1002-0179.202411173

Video：

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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system that primarily affects the optic nerves and spinal cord. Most patients have positive serum antibody of aquaporin-4 (AQP4), which targets the AQP4 protein expressed on the end-feet of astrocytes. Although the prevalence of NMOSD is limited to around (1-2)/100 000, the recurrence rate is high. Repeated and severe immune-mediated attacks can quickly lead to blindness and paralysis if undiagnosed and untreated. While high-dose methylprednisolone and plasma exchange are used in the acute phase, the treatment for recurrent prevention is limited. In recent years, researchers developed several kinds of monoclonal antibodies targeting different nodes of immune pathogenic process, including satralizumab (an interleukin-6 receptor inhibitor), inebilizumab (an antibody against CD19⁺ B cells), and eculizumab (an antibody blocking the C5 component of complement). In several randomized controlled clinical trials, these monoclonal antibodies decreased the relapse rate significantly in NMOSD. These emerging treatments have greatly changed the treatment of NMOSD.

1.	Uzawa A, Oertel FC, Mori M, et al. NMOSD and MOGAD: an evolving disease spectrum. Nat. Rev Neurol, 2024, 20(10): 602-619.
2.	Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol, 2021, 20(1): 60-67.
3.	Tahara M, Oeda T, Okada K, 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.
4.	Jung JS, Bhat RV, Preston GM, et al. Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A, 1994, 91(26): 13052-13056.
5.	Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet, 2004, 364(9451): 2106-2112.
6.	Bennett JL, Pittock SJ, Paul F, et al. B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity. Ann Clin Transl Neurol, 2024, 11(10): 2792-2798.
7.	Majed M, Fryer JP, McKeon A, et al. Clinical utility of testing AQP4-IgG in CSF: guidance for physicians. Neurol Neuroimmunol Neuroinflamm, 2016, 3(3): e231.
8.	Chihara N, Aranami T, Sato W, 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): 3701-3706.
9.	Popescu BF, Lucchinetti CF. Pathology of demyelinating diseases. Annu Rev Pathol, 2012, 7: 185-217.
10.	Carnero Contentti E, Correale J. Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies. J Neuroinflammation, 2021, 18(1): 208.
11.	Arellano G, Loda E, Chen Y, et al. Interferon-γ controls aquaporin 4-specific Th17 and B cells in neuromyelitis optica spectrum disorder. Brain, 2024, 147(4): 1344-1361.
12.	Jarius S, Aktas O, Ayzenberg I, et al. Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis. J Neurol, 2023, 270(7): 3341-3368.
13.	Kümpfel T, Giglhuber K, Aktas O, et al. Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. J Neurol, 2024, 271(1): 141-176.
14.	Carnero Contentti E, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice [Mult Scler Relat Disord. 2020 Oct; 45: 102428]. Mult Scler Relat Disord, 2021, 52: 103026.
15.	Stiebel-Kalish H, Hellmann MA, Mimouni M, et al. Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis?. Neurol Neuroimmunol Neuroinflamm, 2019, 6(4): e572.
16.	Songthammawat T, Srisupa-Olan T, Siritho S, et al. A pilot study comparing treatments for severe attacks of neuromyelitis optica spectrum disorders: intravenous methylprednisolone (IVMP) with add-on plasma exchange (PLEX) versus simultaneous ivmp and PLEX. Mult Scler Relat Disord, 2020, 38: 101506.
17.	Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler, 2016, 22(2): 185-192.
18.	Elsone L, Panicker J, Mutch K, et al. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler, 2014, 20(4): 501-504.
19.	Mealy MA, Shin K, John G, et al. Bevacizumab is safe in acute relapses of neuromyelitis optica. Clin Exp Neuroimmunol, 2015, 6(4): 413-418.
20.	Carnero Contentti E, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice. Mult Scler Relat Disord, 2020, 45: 102428.
21.	Bichuetti DB, Perin MMM, Souza NA, et al. Treating neuromyelitis optica with azathioprine: 20-year clinical practice. Mult Scler, 2019, 25(8): 1150-1161.
22.	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): 1342-1348.
23.	Tahara M, Oeda T, Okada K, 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.
24.	Yu H, Chen Y, Qi Y, et al. First-in-human study of BAT4406F, an ADCC-enhanced fully humanized anti-CD20 monoclonal antibody in patients with neuromyelitis optica spectrum disorders. CNS Neurosci Ther, 2024, 30(11): e70126.
25.	Cree BAC, Bennett JL, Kim HJ, 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): 1352-1363.
26.	Bennett JL, Aktas O, Rees WA, 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.
27.	Ringelstein M, Ayzenberg I, Harmel J, et al. Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol, 2015, 72(7): 756-763.
28.	Araki M, Matsuoka T, Miyamoto K, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology, 2014, 82(15): 1302-1306.
29.	Zhang C, Zhang M, Qiu W, 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.
30.	Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med, 2019, 381(22): 2114-2124.
31.	Traboulsee A, Greenberg BM, Bennett JL, 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): 402-412.
32.	Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med, 2019, 381(7): 614-625.
33.	Davoudi V, Keyhanian K, Bove RM, et al. Immunology of neuromyelitis optica during pregnancy. Neurol Neuroimmunol Neuroinflamm, 2016, 3(6): e288.
34.	Klawiter EC, Bove R, Elsone L, et al. High risk of postpartum relapses in neuromyelitis optica spectrum disorder. Neurology, 2017, 89(22): 2238-2244.
35.	Collongues N, Alves Do Rego C, Bourre B, et al. Pregnancy in patients with AQP4-Ab, MOG-Ab, or double-negative neuromyelitis optica disorder. Neurology, 2021, 96(15): e2006-e2015.
36.	Wang L, Su M, Zhou Z, et al. Analysis of pregnancy-related attacks in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. JAMA Netw Open, 2022, 5(8): e2225438.
37.	Mao-Draayer Y, Thiel S, Mills EA, et al. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nat Rev Neurol, 2020, 16(3): 154-170.
38.	Chitnis T, Ness J, Krupp L, et al. Clinical features of neuromyelitis optica in children: US Network of Pediatric MS Centers report. Neurology, 2016, 86(3): 245-252.

1. Uzawa A, Oertel FC, Mori M, et al. NMOSD and MOGAD: an evolving disease spectrum. Nat. Rev Neurol, 2024, 20(10): 602-619.
2. Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol, 2021, 20(1): 60-67.
3. Tahara M, Oeda T, Okada K, 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.
4. Jung JS, Bhat RV, Preston GM, et al. Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A, 1994, 91(26): 13052-13056.
5. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet, 2004, 364(9451): 2106-2112.
6. Bennett JL, Pittock SJ, Paul F, et al. B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity. Ann Clin Transl Neurol, 2024, 11(10): 2792-2798.
7. Majed M, Fryer JP, McKeon A, et al. Clinical utility of testing AQP4-IgG in CSF: guidance for physicians. Neurol Neuroimmunol Neuroinflamm, 2016, 3(3): e231.
8. Chihara N, Aranami T, Sato W, 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): 3701-3706.
9. Popescu BF, Lucchinetti CF. Pathology of demyelinating diseases. Annu Rev Pathol, 2012, 7: 185-217.
10. Carnero Contentti E, Correale J. Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies. J Neuroinflammation, 2021, 18(1): 208.
11. Arellano G, Loda E, Chen Y, et al. Interferon-γ controls aquaporin 4-specific Th17 and B cells in neuromyelitis optica spectrum disorder. Brain, 2024, 147(4): 1344-1361.
12. Jarius S, Aktas O, Ayzenberg I, et al. Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis. J Neurol, 2023, 270(7): 3341-3368.
13. Kümpfel T, Giglhuber K, Aktas O, et al. Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. J Neurol, 2024, 271(1): 141-176.
14. Carnero Contentti E, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice [Mult Scler Relat Disord. 2020 Oct; 45: 102428]. Mult Scler Relat Disord, 2021, 52: 103026.
15. Stiebel-Kalish H, Hellmann MA, Mimouni M, et al. Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis?. Neurol Neuroimmunol Neuroinflamm, 2019, 6(4): e572.
16. Songthammawat T, Srisupa-Olan T, Siritho S, et al. A pilot study comparing treatments for severe attacks of neuromyelitis optica spectrum disorders: intravenous methylprednisolone (IVMP) with add-on plasma exchange (PLEX) versus simultaneous ivmp and PLEX. Mult Scler Relat Disord, 2020, 38: 101506.
17. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler, 2016, 22(2): 185-192.
18. Elsone L, Panicker J, Mutch K, et al. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler, 2014, 20(4): 501-504.
19. Mealy MA, Shin K, John G, et al. Bevacizumab is safe in acute relapses of neuromyelitis optica. Clin Exp Neuroimmunol, 2015, 6(4): 413-418.
20. Carnero Contentti E, Rojas JI, Cristiano E, et al. Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice. Mult Scler Relat Disord, 2020, 45: 102428.
21. Bichuetti DB, Perin MMM, Souza NA, et al. Treating neuromyelitis optica with azathioprine: 20-year clinical practice. Mult Scler, 2019, 25(8): 1150-1161.
22. 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): 1342-1348.
23. Tahara M, Oeda T, Okada K, 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.
24. Yu H, Chen Y, Qi Y, et al. First-in-human study of BAT4406F, an ADCC-enhanced fully humanized anti-CD20 monoclonal antibody in patients with neuromyelitis optica spectrum disorders. CNS Neurosci Ther, 2024, 30(11): e70126.
25. Cree BAC, Bennett JL, Kim HJ, 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): 1352-1363.
26. Bennett JL, Aktas O, Rees WA, 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.
27. Ringelstein M, Ayzenberg I, Harmel J, et al. Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol, 2015, 72(7): 756-763.
28. Araki M, Matsuoka T, Miyamoto K, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology, 2014, 82(15): 1302-1306.
29. Zhang C, Zhang M, Qiu W, 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.
30. Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med, 2019, 381(22): 2114-2124.
31. Traboulsee A, Greenberg BM, Bennett JL, 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): 402-412.
32. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med, 2019, 381(7): 614-625.
33. Davoudi V, Keyhanian K, Bove RM, et al. Immunology of neuromyelitis optica during pregnancy. Neurol Neuroimmunol Neuroinflamm, 2016, 3(6): e288.
34. Klawiter EC, Bove R, Elsone L, et al. High risk of postpartum relapses in neuromyelitis optica spectrum disorder. Neurology, 2017, 89(22): 2238-2244.
35. Collongues N, Alves Do Rego C, Bourre B, et al. Pregnancy in patients with AQP4-Ab, MOG-Ab, or double-negative neuromyelitis optica disorder. Neurology, 2021, 96(15): e2006-e2015.
36. Wang L, Su M, Zhou Z, et al. Analysis of pregnancy-related attacks in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. JAMA Netw Open, 2022, 5(8): e2225438.
37. Mao-Draayer Y, Thiel S, Mills EA, et al. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nat Rev Neurol, 2020, 16(3): 154-170.
38. Chitnis T, Ness J, Krupp L, et al. Clinical features of neuromyelitis optica in children: US Network of Pediatric MS Centers report. Neurology, 2016, 86(3): 245-252.

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