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

      Highlights

      • The objective of this systematic review was to elucidate the role of rituximab in MOGAD relapse prevention.
      • Systematically searched publications from 2010 to 2021 were reviewed using PRISMA guideline.
      • Rituximab therapy kept 55% of MOGAD patients from relapsing. At follow-up, ARR was lowered by 1.36 and EDSS by 0.52.
      • Because of paucity of data, the safety profile of rituximab for the treatment of MOGAD could not be effectively determined.
      • We concluded that rituximab effectively prevents relapses in MOGAD patients.

      Abstract

      Introduction

      Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD) is neuroimmunological disorder manifesting as episodes of ADEM, optic neuritis, transverse myelitis, brainstem encephalitis, and other CNS manifestations and notably, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Current treatment strategy is high-dose intravenous methylprednisolone followed by maintenance immunotherapy for relapse prevention. The purpose of this study is to systematically create compelling evidence addressing the role of rituximab in relapse prevention among patient with MOGAD.

      Methods

      This study follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. We searched PubMed, Embase, and Google Scholar for English language papers published between 2010 and 2021. Individual study proportions were meta-analyzed to yield the pooled relapse-free patient proportion. Individual studies' mean pre- and post-treatment annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) were used to calculate the overall mean difference.

      Results

      Our meta-analysis includes 13 studies with 238 subjects. After rituximab treatment, 55% (95% CI: 0.49–0.61) of MOGAD patients remained relapse-free. Our study found that after rituximab therapy, ARR was lowered by 1.36 (95% CI 1.02–1.71, p < 0.001). Similarly, we detected a 0.52 (95% CI: 0.08 to 0.96, p = 0.02) difference in EDSS score after starting rituximab medication. Because only a handful of the included studies documented adverse events, the safety profile of rituximab for the treatment of MOGAD could not be effectively determined.

      Conclusion

      Our meta-analysis shows that rituximab effectively prevents relapses in MOGAD patients.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Neuroimmunology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Albassam F.
        • Longoni G.
        • Yea C.
        • Wilbur C.
        • Grover S.A.
        • Yeh E.A.
        Rituximab in children with myelin oligodendrocyte glycoprotein antibody and relapsing neuroinflammatory disease.
        Dev. Med. Child Neurol. 2020; 62: 390-395
        • Borisow N.
        • Mori M.
        • Kuwabara S.
        • Scheel M.
        • Paul F.
        Diagnosis and treatment of NMO spectrum disorder and MOG-encephalomyelitis.
        Front. Neurol. 2018; 9: 888
        • Bruijstens A.L.
        • Wendel E.-M.
        • Lechner C.
        • Bartels F.
        • Finke C.
        • Breu M.
        • et al.
        E.U. paediatric MOG consortium consensus: part 5 - treatment of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.
        Eur. J. Paediatr. Neurol. EJPN Off. J. Eur. Paediatr. Neurol. Soc. 2020 Nov; 29: 41-53
        • Carnero Contentti E.
        • Marrodan M.
        • Correale J.
        Emerging drugs for the treatment of adult MOG-IgG-associated diseases.
        in: Expert Opinion on Emerging Drugs. vol. 26. 2021: 75-78 (England)
        • Chen J.J.
        • Flanagan E.P.
        • Bhatti M.T.
        • Jitprapaikulsan J.
        • Dubey D.
        • Lopez Chiriboga A. (sebastian) S.
        • et al.
        Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder.
        Neurology. 2020; 95: E111-E120
        • Cobo-Calvo A.
        • Sepúlveda M.
        • Rollot F.
        • Armangué T.
        • Ruiz A.
        • Maillart E.
        • et al.
        Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease.
        J. Neuroinflammation. 2019; 16: 1-12
        • 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. [Internet]. 2016 Nov 1; 73 (Available from): 1342-1348
        • Das G.
        • Damotte V.
        • Gelfand J.M.
        • Bevan C.
        • Cree B.A.C.
        • Do L.
        • et al.
        Rituximab before and during pregnancy: a systematic review, and a case series in MS and NMOSD.
        Neurol. Neuroimmunol. Neuroinflam. 2018 May; 5e453
        • de Mol C.L.
        • Wong Y.
        • van Pelt E.D.
        • Wokke B.
        • Siepman T.
        • Neuteboom R.F.
        • et al.
        The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults.
        Mult. Scler. 2020 Jun; 26: 806-814
        • Dos Passos G.R.
        • Oliveira L.M.
        • da Costa B.K.
        • Apostolos-Pereira S.L.
        • Callegaro D.
        • Fujihara K.
        • et al.
        MOG-IgG-associated optic neuritis, encephalitis, and myelitis: lessons learned from neuromyelitis optica spectrum disorder.
        Front. Neurol. 2018; 9: 217
        • Durozard P.
        • Rico A.
        • Boutiere C.
        • Maarouf A.
        • Lacroix R.
        • Cointe S.
        • et al.
        Comparison of the response to rituximab between myelin oligodendrocyte glycoprotein and aquaporin-4 antibody diseases.
        Ann. Neurol. 2020; 87: 256-266
        • 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. [Internet]. 2019; 19 (Available from): 36
        • Hacohen Y.
        • Wong Y.Y.
        • Lechner C.
        • Jurynczyk M.
        • Wright S.
        • Konuskan B.
        • et al.
        Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody–associated disease.
        JAMA Neurol. 2018; 75: 478-487
        • Inan B.
        • Gocmen R.
        • Vural A.
        • Colpak A.I.
        • Meinl E.
        • Karabudak R.
        • et al.
        Myelin oligodendrocyte glycoprotein antibody associated central nervous system demyelinating disease: a tertiary center experience from Turkey.
        Mult. Scler. Relat. Disord. 2020; 44
        • Jarius S.
        • Ruprecht K.
        • Kleiter I.
        • Borisow N.
        • Asgari N.
        • Pitarokoili K.
        • et al.
        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 Neuroinflam. [Internet]. 2016; 13 (Available from:): 1-45
        • Jelcic I.
        • Hanson J.V.M.
        • Lukas S.
        • Weber K.P.
        • Landau K.
        • Pless M.
        • et al.
        Unfavorable structural and functional outcomes in myelin oligodendrocyte glycoprotein antibody-associated optic neuritis.
        J. Neuro-Ophthalmol. 2019; 39: 3-7
        • Lee D.-H.
        • Linker R.A.
        The role of myelin oligodendrocyte glycoprotein in autoimmune demyelination: a target for multiple sclerosis therapy?.
        Expert Opin. Ther. Targets. 2012 May; 16: 451-462
        • Li T.
        • Zhang G.-Q.
        • Li Y.
        • Dong S.-A.
        • Wang N.
        • Yi M.
        • et al.
        Efficacy and safety of different dosages of rituximab for refractory generalized AChR myasthenia gravis: a meta-analysis.
        J. Clin. Neurosci. Off. J. Neurosurg. Soc. Australas. 2021 Mar; 85: 6-12
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • Mulrow C.
        • Gøtzsche P.C.
        • Ioannidis J.P.A.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        J. Clin. Epidemiol. 2009; 62: e1-34
        • Loos J.
        • Pfeuffer S.
        • Pape K.
        • Ruck T.
        • Luessi F.
        • Spreer A.
        • et al.
        MOG encephalomyelitis: distinct clinical, MRI and CSF features in patients with longitudinal extensive transverse myelitis as first clinical presentation.
        J. Neurol. [Internet]. 2020; 267 (Available from): 1632-1642
        • López-Chiriboga A.S.
        • Majed M.
        • Fryer J.
        • Dubey D.
        • McKeon A.
        • Flanagan E.P.
        • et al.
        Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders.
        JAMA Neurol. 2018; 75: 1355-1363
        • Marignier R.
        • Hacohen Y.
        • Cobo-Calvo A.
        • Pröbstel A.-K.
        • Aktas O.
        • Alexopoulos H.
        • et al.
        Myelin-oligodendrocyte glycoprotein antibody-associated disease.
        Lancet Neurol. 2021 Sep; 20: 762-772
        • Nepal G.
        • Shing Y.K.
        • Yadav J.K.
        • Rehrig J.H.
        • Ojha R.
        • Huang D.Y.
        • et al.
        Efficacy and safety of rituximab in autoimmune encephalitis: a meta-analysis.
        Acta Neurol. Scand. 2020 Nov; 142: 449-459
        • O’Connell K.
        • Hamilton-Shield A.
        • Woodhall M.
        • Messina S.
        • Mariano R.
        • Waters P.
        • et al.
        Prevalence and incidence of neuromyelitis optica spectrum disorder, aquaporin-4 antibody-positive NMOSD and MOG antibody-positive disease in Oxfordshire, UK.
        J. Neurol. Neurosurg. Psychiatry. Engl. 2020; 91: 1126-1128
        • O’Connor K.C.
        • McLaughlin K.A.
        • De Jager P.L.
        • Chitnis T.
        • Bettelli E.
        • Xu C.
        • et al.
        Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein.
        Nat. Med. 2007 Feb; 13: 211-217
        • Pham-Dinh D.
        • Mattei M.G.
        • Nussbaum J.L.
        • Roussel G.
        • Pontarotti P.
        • Roeckel N.
        • et al.
        Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex.
        Proc. Natl. Acad. Sci. U. S. A. 1993 Sep; 90: 7990-7994
        • Ramanathan S.
        • Mohammad S.
        • Tantsis E.
        • Nguyen T.K.
        • Merheb V.
        • Fung V.S.C.
        • et al.
        Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.
        J. Neurol. Neurosurg. Psychiatry. 2018; 89: 127-137
        • Rigal J.
        • Ciron J.
        • Lépine Z.
        • Biotti D.
        Late-onset neutropenia after RITUXIMAB therapy for multiple sclerosis, neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases.
        Mult. Scler. Relat. Disord. 2020; 41: 2019-2021
        • Sechi E.
        • Krecke K.N.
        • Messina S.A.
        • Buciuc M.
        • Pittock S.J.
        • Chen J.J.
        • et al.
        Comparison of MRI lesion evolution in different central nervous system demyelinating disorders.
        Neurology [Internet]. 2021 Sep 14; 97 (Available from:): e1097-e1109
        • 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 Apr; 19: 298-306
        • Takai Y.
        • Misu T.
        • Kaneko K.
        • Chihara N.
        • Narikawa K.
        • Tsuchida S.
        • et al.
        Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study.
        Brain. 2020 May; 143: 1431-1446
        • Vollmer B.L.
        • Wallach A.I.
        • Corboy J.R.
        • Dubovskaya K.
        • Alvarez E.
        • Kister I.
        Serious safety events in rituximab-treated multiple sclerosis and related disorders.
        Ann. Clin. Transl. Neurol. 2020 Sep; 7: 1477-1487
        • 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 May; 50102843
        • Whittam D.H.
        • Cobo-Calvo A.
        • Lopez-Chiriboga A.S.
        • Pardo S.
        • Gornall M.
        • Cicconi S.
        • et al.
        Treatment of MOG-IgG-associated disorder with rituximab: an international study of 121 patients.
        Mult. Scler. Relat. Disord. 2020; 44
        • Whittam D.H.
        • Karthikeayan V.
        • Gibbons E.
        • Kneen R.
        • Chandratre S.
        • Ciccarelli O.
        • et al.
        Treatment of MOG antibody associated disorders: results of an international survey.
        J. Neurol. 2020 Dec; 267: 3565-3577
        • Wingerchuk D.M.
        • Banwell B.
        • Bennett J.L.
        • Cabre P.
        • Carroll W.
        • Chitnis T.
        • et al.
        International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.
        Neurology. 2015 Jul; 85: 177-189
        • Zhao C.
        • Pu M.
        • Chen D.
        • Shi J.
        • Li Z.
        • Guo J.
        • et al.
        Effectiveness and safety of rituximab for refractory myasthenia gravis: a systematic review and single-arm meta-analysis [internet].
        Front. Neurol. 2021; 12 (Available from): 1827