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Anti-B-cell therapy in patients with neuromyelitis optica spectrum disorders

https://doi.org/10.14412/2074-2711-2021-4-18-24

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Abstract

Neuromyelitis optica spectrum disorders (NMOSDs) are a group of central nervous system autoimmune diseases characterized by similar clinical manifestations, optic neuritis, and transverse myelitis being the most frequent among them. In most cases, the pathogenesis of NMOSDs is associated with autoantibodies to aquaporin-4 (AQP4-IgG). However, AQP4-IgG is not detected in at least 10-20% of patients with NMOSDs. In this subgroup and in patients with isolated transverse myelitis or optic neuritis, IgG antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) were detected. Patients seronegative for both AQP4-IgG and MOG-IgG have also been described.

Objective: to evaluate rituximab (RTX) effectiveness in preventing relapses and disability in patients with NMOSDs.

Patients and methods. The study included 27 patients with NMOSDs (9 men and 18 women) aged 20-51 years who received RTX in 2019-2021. The treatment protocol included intravenous infusions of 1000 mg of RTX on the 1st and 15th days, the second and subsequent courses (maintenance therapy) - intravenous infusions of 1000 mg of RTX once every six months. Treatment effectiveness was assessed by the average annualized relapse rate, the median changes of the Expanded Disability Status Scale (EDSS), and based on the magnetic resonance imaging (MRI) changes.

Results and discussion. The annualized relapse rate at baseline and 18 months after the start of treatment was: all patients (n=27) — 0.6±0.3 and 0.07±0.27(p<0.0001); AQP4-IgG+ patients (n=6) — 1.1±0.9 and 0.17±0.41 (p=0.028); MOG-IgG+ patients (n=14) — 0.4±0.3 and 0.07±0.28(p=0.001); AQP4-IgG-, MOG-IgG-patients (n=7) — 0.8±0.4 and 0.0±0.0 (p=0.018). The EDSSscore at baseline and 18months after the start of treatment was: all patients — 4.5 [3.25; 6.0] and 4.0 [3.0; 5.75] (p=0.679); AQP4-IgG+ — 3.5 [2.625; 4.75] and 3.5 [2.5; 4.5] (p=0.869); MOG-IgG+ - 5.5[3.75; 6.5] and 5.5[2.75; 6.25] (p=0.465); AQP4-IgG-, MOG-IgG- - 4.0[3.75; 5.25] and 3.5[3.0; 3.5] (p=0.043). We observed two clinical relapses during the study period: one in an AQP4-IgG+ male and another one in a MOG-IgG+ woman. There was a significant decrease in the annualized relapse rate in all groups. The disability indicator did not increase during the study period, and in AQP4-IgG and MOG-IgG seronegative patients, it slightly but significantly decreased. Brain and spinal cord MRI monitoring during the treatment period revealed new active foci only in two patients with clinical relapses.

Conclusion. RTX treatment in NMOSDs is reasonably efficient and safe, but with the obligatory prior patient evaluation and monitoring of treatment results.

About the Authors

S. V. Kotov
M.F. Vladimirsky Moscow Regional Research Clinical Institute
Russian Federation

61/2, Shchepkin St., Build. 1, Moscow 129110.


Competing Interests:

There are no conflicts of interest. 



E. S. Novikova
M.F. Vladimirsky Moscow Regional Research Clinical Institute
Russian Federation

61/2, Shchepkin St., Build. 1, Moscow 129110.


Competing Interests:

There are no conflicts of interest. 



A. S. Kotov
M.F. Vladimirsky Moscow Regional Research Clinical Institute
Russian Federation

Aleksey Sergeevich Kotov.

61/2, Shchepkin St., Build. 1, Moscow 129110.


Competing Interests:

There are no conflicts of interest. 



References

1. Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation. 2013 Jan 15;10:8. doi: 10.1186/1742-2094-10-8

2. Lucchinetti CF, Guo Y, Popescu BF, et al. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol. 2014 Jan;24(1):83-97. doi: 10.1111/bpa.12099

3. Wingerchuk DM, Banwell B, Bennett JL, et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-89. doi: 10.1212/WNL.0000000000001729

4. Kotov AS. Anti-MOG syndrome: two case reports. Nevrologiya, neyropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(1):84-8. doi: 10.14412/2074-2711-2019-1-84-88 (In Russ.).

5. Kitley J, Waters P, Woodhall M, et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol. 2014;71(3):276-83. doi: 10.1001/jamaneurol.2013.5857

6. Jarius S, Ruprecht K, Kleiter I, et al; in cooperation with the Neuromyelitis Optica Study Group (NEMOS). MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016;13(1):280. doi: 10.1186/s12974-016-0718-0

7. Pandit L, Sato DK, Mustafa S, et al. Serological markers associated with neuromyelitis optica spectrum disorders in South India. Ann Indian Acad Neurol. 2016 Oct-Dec;19(4):505-9. doi: 10.4103/09722327.192389

8. Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014;82(6):474-81. doi: 10.1212/WNL.0000000000000101

9. Cross H, Sabiq F, Ackermans N, et al. Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Positive Patients in a Multi-Ethnic Canadian Cohort. Front Neurol. 2021 Jan 12;11:525933. doi: 10.3389/fneur.2020.525933. eCollection 2020.

10. Tokareva YuV, Kotov AS, Panteleeva MV, Bunak MS. Neuromyelitis optica spectrum disorders in pediatric patients. Nevrologiya, neyropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):60-4. doi: 10.14412/2074-2711-2018-1-60-64 (In Russ.).

11. Fujihara K. Neuromyelitis optica spectrum disorders: still evolving and broadening. Curr Opin Neurol. 2019 Jun;32(3):385-94. doi: 10.1097/WCO.0000000000000694

12. Borisow N, Mori M, Kuwabara S, et al. Diagnosis and Treatment of NMO Spectrum Disorder and MOG-Encephalomyelitis. Front Neurol. 2018 Oct 23;9:888. doi: 10.3389/fneur.2018.00888. eCollection 2018.

13. Simaniv TO, Vasiliev AV, Askarova LSh, Zakharova MN. Neuromyelitis optica and neuromyelitis optica spectrum disorders. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2019;119(10-2):35-48. doi: 10.17116/jnevro20191191035 (In Russ.).

14. Kimbrough DJ, Fujihara K, Jacob A, et al; GJCF-CC&BR. Treatment of Neuromyelitis Optica: Review and Recommendations. Mult Scler Relat Disord. 2012 Oct;1(4):180-7. doi: 10.1016/j.msard.2012.06.002

15. Kaneko K, Sato DK, Nakashima I, et al. CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications. J Neurol Neurosurg Psychiatry. 2018 Sep;89(9):927-36. doi: 10.1136/jnnp-2018-317969. Epub 2018 Jun 6.

16. Axtell RC, Raman C, Steinman L. Type I interferons: beneficial in Th1 and detrimental in Th17 autoimmunity. Clin Rev Allergy Immunol. 2013 Apr;44(2):114-20. doi: 10.1007/s12016-011-8296-5

17. Kleiter I, Gahlen A, Borisow N, et al; Neuromyelitis Optica Study Group. Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016 Feb;79(2):206-16. doi: 10.1002/ana.24554. Epub 2015 Nov 26.

18. 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 Feb;22(2):185-92. doi: 10.1177/1352458515581438. Epub 2015 Apr 28.

19. Ellwardt E, Ellwardt L, Bittner S, Zipp F. Monitoring B-cell repopulation after depletion therapy in neurologic patients. Neurol Neuroimmunol Neuroinflamm. 2018 Apr 25;5(4):e463. doi: 10.1212/NXI.0000000000000463. eCollection 2018 Jul.

20. Evangelopoulos ME, Andreadou E, Koutsis G, et al. Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell monitoring. A six-year follow-up. J Neurol Sci. 2017 Jan 15;372:92-6. doi: 10.1016/j.jns.2016.11.016. Epub 2016 Nov 10.

21. 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 May;19(5):402-12. doi: 10.1016/S1474-4422(20)30078-8

22. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Aug 15;381(7):614-25. doi: 10.1056/NEJMoa1900866. Epub 2019 May 3.

23. Cree BAC, Bennett JL, Kim HJ, et al; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019 Oct 12;394(10206):1352-63. doi: 10.1016/S0140-6736(19)31817-3. Epub 2019 Sep 5.

24. Jurynczyk M, Weinshenker B, Akman-Demir G, et al. Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes. J Neurol. 2016 Jan;263(1):140-9. doi: 10.1007/s00415-015-7952-8. Epub 2015 Nov 3.

25. Cree BA, Lamb S, Morgan K, et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology. 2005 Apr 12;64(7):1270-2. doi: 10.1212/01.WNL.0000159399.81861.D5

26. 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 Nov 1;73(11):1342-8. doi: 10.1001/jamaneurol.2016.1637

27. Gao F, Chai B, Gu C, et al. Effectiveness of rituximab in neuromyelitis optica: a meta-analysis. BMC Neurol. 2019 Mar 6;19(1):36. doi: 10.1186/s12883-019-1261-2

28. Ciron J, Audoin B, Bourre B, et al; NOMADMUS group, under the aegis of OFSEP, SFSEP. Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders. Rev Neurol (Paris). 2018 Apr;174(4):255-64. doi: 10.1016/j.neurol.2017.11.005. Epub 2018 Mar 30.

29. Schmetzer O, Lakin E, Roediger B, et al. Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder. Front Neurol. 2021;12:635419. doi: 10.3389/fneur.2021.635419


For citation:


Kotov S.V., Novikova E.S., Kotov A.S. Anti-B-cell therapy in patients with neuromyelitis optica spectrum disorders. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(4):18-24. https://doi.org/10.14412/2074-2711-2021-4-18-24

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)