Interleukin-6 targeting antibodies for the treatment of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD): A review of current literature

Siddarth R. Ganesh; Orion Yedidia; Krupa Pandey; Carmenrita Infortuna; Charitha Madiraju; Florian P. Thomas; Fortunato Battaglia; Siddarth R. Ganesh; Orion Yedidia; Krupa Pandey; Carmenrita Infortuna; Charitha Madiraju; Florian P. Thomas; Fortunato Battaglia

doi:10.3934/Neuroscience.2025008

AIMS Neuroscience

2025, Volume 12, Issue 2: 113-139. doi: 10.3934/Neuroscience.2025008

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Interleukin-6 targeting antibodies for the treatment of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD): A review of current literature

1.
Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
2.
Department of Neurology, Hackensack University Medical Center and Hackensack Meridian School of Medicine, Nutley, NJ, USA
3.
Department of Cognitive Sciences, Psychology, Educational and Cultural Studies, University of Messina, Messina, Italy
These two authors contributed equally.

Received: 23 December 2024 Revised: 24 April 2025 Accepted: 28 April 2025 Published: 08 May 2025

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune inflammatory demyelinating disorder that can manifest as optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. Although typically monophasic, relapsing cases are more common in adults. Current treatments include corticosteroids, intravenous immunoglobulin, immune-suppressive drugs, and plasma exchange, but there is emerging interest in the use of interleukin-6 (IL-6) inhibitors to prevent relapses such as tocilizumab and satralizumab. This review analyzed 24 studies on IL-6 inhibitors for MOGAD, including case reports, case series, and retrospective studies with at least one MOGAD patient. Tocilizumab demonstrated significant efficacy, with most studies reporting reduced annualized relapse rates (ARR), prolonged relapse-free periods, and improved neurological outcomes, including stabilization or recovery of vision, motor function, and magnetic resonance imaging (MRI) lesion resolution. Satralizumab also showed potential, though data were more limited. While IL-6 inhibitors appear beneficial for steroid-dependent or treatment-resistant MOGAD, the existing data are limited to small, observational studies. Larger controlled trials are needed to establish their long-term efficacy and safety.
- MOGAD,
- Interleukin 6,
- tocilizumab,
- satralizumab,
- efficacy
Citation: Siddarth R. Ganesh, Orion Yedidia, Krupa Pandey, Carmenrita Infortuna, Charitha Madiraju, Florian P. Thomas, Fortunato Battaglia. Interleukin-6 targeting antibodies for the treatment of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOGAD): A review of current literature[J]. AIMS Neuroscience, 2025, 12(2): 113-139. doi: 10.3934/Neuroscience.2025008

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Abstract

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune inflammatory demyelinating disorder that can manifest as optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. Although typically monophasic, relapsing cases are more common in adults. Current treatments include corticosteroids, intravenous immunoglobulin, immune-suppressive drugs, and plasma exchange, but there is emerging interest in the use of interleukin-6 (IL-6) inhibitors to prevent relapses such as tocilizumab and satralizumab. This review analyzed 24 studies on IL-6 inhibitors for MOGAD, including case reports, case series, and retrospective studies with at least one MOGAD patient. Tocilizumab demonstrated significant efficacy, with most studies reporting reduced annualized relapse rates (ARR), prolonged relapse-free periods, and improved neurological outcomes, including stabilization or recovery of vision, motor function, and magnetic resonance imaging (MRI) lesion resolution. Satralizumab also showed potential, though data were more limited. While IL-6 inhibitors appear beneficial for steroid-dependent or treatment-resistant MOGAD, the existing data are limited to small, observational studies. Larger controlled trials are needed to establish their long-term efficacy and safety.

Conflict of interest

The authors declare no conflicts of interest.

Authors' contributions

SRG, OY, KP, CM, and FB planned the literature search; SRG and OY performed the literature search and drafted the first version of the manuscript; KP, CM, and FB reviewed the methodology; SRG, OY, KP, CI, CM, FPT, and FB contributed to data interpretation; SRG, OY, KP, CI, CM, FPT, and FB revised the manuscript critically. All authors approved the final version of the manuscript.

References

[1]	Hor JY, Fujihara K (2023) Epidemiology of myelin oligodendrocyte glycoprotein antibody-associated disease: a review of prevalence and incidence worldwide. Front Neurol 14: 1260358. https://doi.org/10.3389/fneur.2023.1260358
[2]	Banwell B, Bennett JL, Marignier R, et al. (2023) Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol 22: 268-282. https://doi.org/10.1016/S1474-4422(22)00431-8
[3]	Fadda G, Flanagan EP, Cacciaguerra L, et al. (2022) Myelitis features and outcomes in CNS demyelinating disorders: comparison between multiple sclerosis, MOGAD, and AQP4-IgG-positive NMOSD. Front Neurol 13: 1011579. https://doi.org/10.3389/fneur.2022.1011579
[4]	Uzawa A, Oertel FC, Mori M, et al. (2024) NMOSD and MOGAD: an evolving disease spectrum. Nat Rev Neurol 20: 602-619. https://doi.org/10.1038/s41582-024-01014-1
[5]	Schoeps VA, Virupakshaiah A, Waubant E (2024) Unveiling the Performance of Proposed MOGAD Diagnostic Criteria. Neurology 103: e209551. https://doi.org/10.1212/WNL.0000000000209551
[6]	Bartels F, Lu A, Oertel FC, et al. (2021) Clinical and neuroimaging findings in MOGAD–MRI and OCT. Clin Exp Immunol 206: 266-281. https://doi.org/10.1111/cei.13641
[7]	Perez-Giraldo G, Caldito NG, Grebenciucova E (2023) Transverse myelitis in myelin oligodendrocyte glycoprotein antibody-associated disease. Front Neurol 14: 1210972. https://doi.org/10.3389/fneur.2023.1210972
[8]	Ciron J, Cobo-Calvo A, Audoin B, et al. (2020) Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: a retrospective multicentric study. Mult Scler 26: 936-944. https://doi.org/10.1177/1352458519849511
[9]	Sun X, Liu M, Luo X, et al. (2022) Clinical characteristics and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody-associated diseases in China. BMC Pediatr 22: 666. https://doi.org/10.1186/s12887-022-03679-3
[10]	Armangue T, Olivé-Cirera G, Martínez-Hernandez E, et al. (2020) Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study. Lancet Neurol 19: 234-246. https://doi.org/10.1016/S1474-4422(19)30488-0
[11]	Satukijchai C, Mariano R, Messina S, et al. (2022) Factors associated with relapse and treatment of myelin oligodendrocyte glycoprotein antibody–associated disease in the United Kingdom. JAMA Netw Open 5: e2142780. https://doi.org/10.1001/jamanetworkopen.2021.42780
[12]	Wolf AB, Palace J, Bennett JL (2023) Emerging principles for treating myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Curr Treat Option Ne 25: 437-453. https://doi.org/10.1007/s11940-023-00776-1
[13]	Lai QL, Zhang YX, Cai MT, et al. (2021) Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody-associated disease: a systematic review and meta-analysis. Ther Adv Neurol Disord 14: 17562864211054157. https://doi.org/10.1177/17562864211054157
[14]	Lerch M, Bauer A, Reindl M (2023) The Potential Pathogenicity of Myelin Oligodendrocyte Glycoprotein Antibodies in the Optic Pathway. J Neuroophthalmol 43: 5-16. https://doi.org/10.1097/WNO.0000000000001772
[15]	Gontika MP, Anagnostouli MC (2018) Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses. Mult Scler Int 2018: 8487471. https://doi.org/10.1155/2018/8487471
[16]	Weber J, Bernsdorff N, Robinson T, et al. (2021) Diagnosis of multiple sclerosis in times of MOG and AQP4 autoantibody testing - A monocentric study. J Neurol Sci 421: 117289. https://doi.org/10.1016/j.jns.2020.117289
[17]	Sheppard M, Laskou F, Stapleton PP, et al. (2017) Tocilizumab (actemra). Hum Vaccin Immunother 13: 1972-1988. https://doi.org/10.1080/21645515.2017.1316909
[18]	Schirmer M, Muratore F, Salvarani C (2018) Tocilizumab for the treatment of giant cell arteritis. Expert Rev Clin Immunol 14: 339-349. https://doi.org/10.1080/1744666X.2018.1468251
[19]	Si S, Teachey DT (2020) Spotlight on tocilizumab in the treatment of CAR-T-cell-induced cytokine release syndrome: clinical evidence to date. Ther Clin Risk Manag 16: 705-714. https://doi.org/10.2147/TCRM.S223468
[20]	Heo YA (2020) Satralizumab: First Approval. Drugs 80: 1477-1482. https://doi.org/10.1007/s40265-020-01380-2
[21]	Zhang C, Zhang M, Qiu W, et al. (2020) 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 19: 391-401. https://doi.org/10.1016/S1474-4422(20)30070-3
[22]	Sbragia E, Boffa G, Varaldo R, et al. (2024) An aggressive form of MOGAD treated with aHSCT: A case report. Mult Scler 30: 612-616. https://doi.org/10.1177/13524585231213792
[23]	Masuccio FG, Lo Re M, Bertolotto A, et al. (2020) Benign SARS-CoV-2 infection in MOG-antibodies associated disorder during tocilizumab treatment. Mult Scler Relat Disord 46: 102592. https://doi.org/10.1016/j.msard.2020.102592
[24]	McLendon LA, Gambrah-Lyles C, Viaene A, et al. (2023) Dramatic Response to Anti-IL-6 Receptor Therapy in Children With Life-Threatening Myelin Oligodendrocyte Glycoprotein-Associated Disease. Neurol Neuroimmunol Neuroinflamm 10: e200150. https://doi.org/10.1212/NXI.0000000000200150
[25]	Kwon O, Choi J (2024) Effective Prevention with Maintenance Treatment of Tocilizumab in Pediatric MOG-IgG Associated Disorder (MOGAD) Relapse. Ann Child Neurol 32: 197-200. https://doi.org/10.26815/acn.2024.00514
[26]	Kang YR, Kim KH, Hyun JW, et al. (2024) Efficacy of tocilizumab in highly relapsing MOGAD with an inadequate response to intravenous immunoglobulin therapy: A case series. Mult Scler Relat Disord 91: 105859. https://doi.org/10.1016/j.msard.2024.105859
[27]	Elsbernd PM, Hoffman WR, Carter JL, et al. (2021) Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): A case-series and review. Mult Scler Relat Disord 48: 102696. https://doi.org/10.1016/j.msard.2020.102696
[28]	Kim S, Kim S, Jang Y, et al. (2023) Leptomeningeal Enhancement, a Phenotype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease With Caudate Nucleus Involvement: A Case Report and Literature Review. J Clin Neurol 19: 210-213. https://doi.org/10.3988/jcn.2022.0307
[29]	Virupakshaiah A, Moseley CE, Elicegui S, et al. (2024) Life-Threatening MOG Antibody-Associated Hemorrhagic ADEM With Elevated CSF IL-6. Neurol Neuroimmunol Neuroinflamm 11: e200243. https://doi.org/10.1212/NXI.0000000000200243
[30]	Lee Y, Ahn SJ, Lee HS, et al. (2023) Myelin oligodendrocyte glycoprotein antibody-associated encephalitis after severe acute respiratory syndrome coronavirus 2 infection: a case report and retrospective case reviews. Encephalitis 3: 71-77. https://doi.org/10.47936/encephalitis.2022.00129
[31]	Nagahata K, Suzuki S, Yokochi R, et al. (2022) Recurrent Optic Perineuritis With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Complicated With Granulomatous Polyangiitis. Cureus 14: e25239. https://doi.org/10.7759/cureus.25239
[32]	Smoot K, Chen C, Cohan S (2021) Recurrent relapse after 20 years in a patient with MOG antibody disease: A case report. Neuroimmunol Rep 1: 100042. https://doi.org/10.1016/j.nerep.2021.100042
[33]	Kroenke E, Ankar A, Malani Shukla N (2022) Refractory MOG-Associated Demyelinating Disease in a Pediatric Patient. Child Neurol Open 9: 2329048X221079093. https://doi.org/10.1177/2329048X221079093
[34]	Novi G, Gastaldi M, Franciotta D, et al. (2019) Tocilizumab in MOG-antibody spectrum disorder: a case report. Mult Scler Relat Disord 27: 312-314. https://doi.org/10.1016/j.msard.2018.11.012
[35]	Schirò G, Iacono S, Salemi G, et al. (2024) The pharmacological management of myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD): an update of the literature. Expert Rev Neurother 24: 985-996. https://doi.org/10.1080/14737175.2024.2385941
[36]	Hayward-Koennecke H, Reindl M, Martin R, et al. (2019) Tocilizumab treatment in severe recurrent anti-MOG-associated optic neuritis. Neurology 92: 765-767. https://doi.org/10.1212/WNL.0000000000007312
[37]	Dayrit KC, Chua-Ley EO (2024) Use of Tocilizumab Followed by Rituximab Desensitization on Relapsing Myelin Oligodendrocyte Antibody Disease: A Case Report. Cureus 16: e52374. https://doi.org/10.7759/cureus.52374
[38]	Bilodeau PA, Vishnevetsky A, Molazadeh N, et al. (2024) Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. Mult Scler 30: 357-368. https://doi.org/10.1177/13524585241226830
[39]	Lotan I, Charlson RW, Ryerson LZ, et al. (2020) Effectiveness of subcutaneous tocilizumab in neuromyelitis optica spectrum disorders. Mult Scler Relat Disord 39: 101920. https://doi.org/10.1016/j.msard.2019.101920
[40]	Rempe T, Rodriguez E, Elfasi A, et al. (2024) Frequency, characteristics, predictors and treatment of relapsing myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Mult Scler Relat Disord 87: 105672. https://doi.org/10.1016/j.msard.2024.105672
[41]	Ringelstein M, Ayzenberg I, Lindenblatt G, et al. (2021) Interleukin-6 receptor blockade in treatment-refractory MOG-IgG–associated disease and neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm 9: e1100. https://doi.org/10.1212/NXI.0000000000001100
[42]	Guzmán J, Vera F, Soler B, et al. (2023) Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) in Chile: lessons learned from challenging cases. Mult Scler Relat Disord 69: 104442. https://doi.org/10.1016/j.msard.2022.104442
[43]	Rigal J, Pugnet G, Ciron J, et al. (2020) Off-label use of tocilizumab in neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases: A case-series. Mult Scler Relat Disord 46: 102483. https://doi.org/10.1016/j.msard.2020.102483
[44]	Powers JH, Mooneyham GC (2020) Psychiatric Symptoms in Pediatric Patients With Myelin-Oligodendrocyte-Glycoprotein-Immunoglobulin G-Antibody Positive Autoimmune Encephalitis: A Case Series. Psychosomatics 61: 846-850. https://doi.org/10.1016/j.psym.2019.12.002
[45]	Jelcic I, Hanson JV, Lukas S, et al. (2019) Unfavorable structural and functional outcomes in myelin oligodendrocyte glycoprotein antibody–associated optic neuritis. J Neuroophthalmol 39: 3-7. https://doi.org/10.1097/WNO.0000000000000669
[46]	Hutto SK, Cavanagh JJ (2025) Advances in Diagnosis and Management of Atypical Demyelinating Diseases. Med Clin North Am 109: 425-441. https://doi.org/10.1016/j.mcna.2024.09.011
[47]	Schirò G, Iacono S, Andolina M, et al. (2023) Tocilizumab treatment in MOGAD: a case report and literature review. Neurol Sci 45: 1429-1436. https://doi.org/10.1007/s10072-023-07189-7
[48]	Schett G (2018) Physiological effects of modulating the interleukin-6 axis. Rheumatology (Oxford) 57: ii43-ii50. https://doi.org/10.1093/rheumatology/kex513
[49]	Yoshida Y, Tanaka T (2014) Interleukin 6 and rheumatoid arthritis. Biomed Res Int 2014: 698313. https://doi.org/10.1155/2014/698313
[50]	Tackey E, Lipsky PE, Illei GG (2004) Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus 13: 339-343. https://doi.org/10.1191/0961203304lu1023oa
[51]	Koutsouraki E, Hatzifilipou E, Michmizos D, et al. (2011) Increase in interleukin-6 levels is related to depressive phenomena in the acute (relapsing) phase of multiple sclerosis. J Neuropsychiatry Clin Neurosci 23: 442-448. https://doi.org/10.1176/jnp.23.4.jnp442
[52]	Schneider A, Long SA, Cerosaletti K, et al. (2013) In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T(regs) involves IL-6-mediated signaling. Sci Transl Med 5: 170ra15. https://doi.org/10.1126/scitranslmed.3004970
[53]	Fujihara K, Bennett JL, de Seze J, et al. (2020) Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology. Neurol Neuroimmunol Neuroinflamm 7: e841. https://doi.org/10.1212/NXI.0000000000000841
[54]	Takeshita Y, Fujikawa S, Serizawa K, et al. (2021) New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD. Neurol Neuroimmunol Neuroinflamm 8: e1076. https://doi.org/10.1212/NXI.0000000000001076
[55]	Haramati A, Rechtman A, Zveik O, et al. (2022) IL-6 as a marker for NMOSD disease activity. J Neuroimmunol 370: 577925. https://doi.org/10.1016/j.jneuroim.2022.577925
[56]	Corbali O, Chitnis T (2023) Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease. Front Neurol 14: 1137998. https://doi.org/10.3389/fneur.2023.1137998
[57]	Yao M, Wang W, Sun J, et al. (2024) The landscape of PBMCs in AQP4-IgG seropositive NMOSD and MOGAD, assessed by high dimensional mass cytometry. CNS Neurosci Ther 30: e14608. https://doi.org/10.1111/cns.14608
[58]	Horellou P, de Chalus A, Giorgi L, et al. (2021) Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children. Front Immunol 12: 679770. https://doi.org/10.3389/fimmu.2021.679770
[59]	Moseley CE, Virupakshaiah A, Forsthuber TG, et al. (2024) MOG CNS Autoimmunity and MOGAD. Neurol Neuroimmunol Neuroinflamm 11: e200275. https://doi.org/10.1212/NXI.0000000000200275
[60]	Whittam DH, Karthikeayan V, Gibbons E, et al. (2020) Treatment of MOG antibody associated disorders: results of an international survey. J Neurol 267: 3565-3577. https://doi.org/10.1007/s00415-020-10026-y
[61]	Nepal G, Kharel S, Coghlan MA, et al. (2022) Safety and efficacy of rituximab for relapse prevention in myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD): A systematic review and meta-analysis. J Neuroimmunol 364: 577812. https://doi.org/10.1016/j.jneuroim.2022.577812
[62]	Yong KP, Kim HJ (2021) Demystifying MOGAD and Double Seronegative NMOSD Further With IL-6 Blockade. Neurol Neuroimmunol Neuroinflamm 9: e1110. https://doi.org/10.1212/NXI.0000000000001110
[63]	Cochrane LibrarySafety and Efficacy of Tocilizumab in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, NCT06452537 (2024). [cited 2025 May 08]. Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02709117/full
[64]	Cochrane LibraryA Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, NCT05271409 (2022). [cited 2025 May 08]. Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-02374734/full
[65]	Kothur K, Wienholt L, Tantsis EM, et al. (2016) B Cell, Th17, and Neutrophil Related Cerebrospinal Fluid Cytokine/Chemokines Are Elevated in MOG Antibody Associated Demyelination. PLoS One 11: e0149411. https://doi.org/10.1371/journal.pone.0149411

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