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Research paper
Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination
  1. Sudarshini Ramanathan1,2,3,
  2. Shekeeb Mohammad1,2,4,
  3. Esther Tantsis1,2,5,
  4. Tina Kim Nguyen1,2,
  5. Vera Merheb1,2,
  6. Victor S C Fung3,6,
  7. Owen Bruce White7,8,
  8. Simon Broadley9,10,
  9. Jeannette Lechner-Scott11,12,
  10. Steve Vucic3,6,
  11. Andrew P D Henderson3,6,13,
  12. Michael Harry Barnett14,
  13. Stephen W Reddel14,
  14. Fabienne Brilot1,2,14,
  15. Russell C Dale4,14
  16. on behalf of the Australasian and New Zealand MOG Study Group
    1. 1 Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital, Westmead, New South Wales, Australia
    2. 2 Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
    3. 3 Department of Neurology, Westmead Hospital, Westmead, New South Wales, Australia
    4. 4 TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital, Westmead, New South Wales, Australia
    5. 5 Department of Clinical Medicine, Macquarie University, Sydney, New South Wales, Australia
    6. 6 University of Sydney, Sydney, New South Wales, Australia
    7. 7 Ocular Motor Research Laboratory, University of Melbourne, Melbourne, Victoria, Australia
    8. 8 Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia
    9. 9 School of Medicine, Griffith University, Gold Coast, Queensland, Australia
    10. 10 Department of Neurology, Gold Coast University Hospital, Gold Coast, Queensland, Australia
    11. 11 Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia
    12. 12 Faculty of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia
    13. 13 Department of Ophthalmology, Westmead Hospital, Sydney, New South Wales, Australia
    14. 14 Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia
    1. Correspondence to Russell C Dale, Clinical School, the Children’s Hospital at Westmead, Locked Bag 4001, NSW 2145, Australia; russell.dale{at}health.nsw.gov.au

    Abstract

    Objective We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.

    Methods We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.

    Results The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077).

    Conclusion Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.

    • myelin oligodendrocyte glycoprotein antibodies
    • optic neuritis
    • acute disseminated encephalomyelitis
    • therapy
    • outcomes

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • FB and RCD contributed equally.

    • Contributors Study conception and design: SRa, FB, RCD. Sample acquisition: all authors. Acquisition of laboratory data: SRa, TKN, VM, FB. Acquisition of clinical data: SRa, RCD. Study supervision, data analysis and interpretation: SRa, RCD. Writing of first draft: SRa, RCD. Editing and revising final draft for intellectual content: all authors.

    • Funding This work was supported by the National Health and Medical Research Council (NHMRC) (Australia), the Petre Foundation (Australia), Multiple Sclerosis Research Australia (MSRA) (Australia), the National Blood Authority IVIg grant (Australia), the Brain Foundation and the Sydney Research Excellence Initiative 2020 Neuroimmunology Group (University of Sydney, Australia).

    • Competing interests Dr SR has received research funding from the National Health and Medical Research Council, the Petre Foundation and the Brain Foundation (Australia). Dr SM has received a scholarship from the National Health and Medical Research Council (Australia) and funding from the National Blood Authority IVIg grant. SB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis and Sanofi-Genzyme, has received speakers honoraria from Biogen-Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen-Idec, Novartis and Genzyme and was the recipient of an unencumbered research grant from Biogen-Idec. JL-S has accepted travel compensation from Novartis, Biogen and Merck-Serono. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Bayer Health Care, Biogen, Sanofi-Genzyme, Merck, Novartis and Teva. SR reports grants and personal fees from Sanofi-Genzyme, personal fees and departmental support from the Government of Australia, Baxter, Biogen, CSL and Merck; and departmental support from Novartis, outside the subject of the submitted work. Associate Professor FB has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia and the National Health Medical Research Council (Australia). RD has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation and the National Health Medical Research Council (Australia). Dr RCD has received honoraria from Biogen-Idec as an invited speaker. Dr JLB has received compensation for education travel, honoraria for talks and advisory boards from Biogen, Teva, Merck-Serono, Sanofi-Genzyme, Novartis and Roche. Dr AC has received honoraria for attendance at advisory boards from Biogen and is an investigator in clinical trials sponsored by Biogen and Pfizer. Dr PC has accepted travel compensation from, Biogen and Merck Serono, and fellowship funding from Novartis/Biogen. Associate Professor CLF has received payment from Roche as a consultant. Dr MPM has received travel grants, speaking honoraria and unconditional research funding from Bayer, Biogen and Merck. Professor IES is supported by NHMRC Program Grant (1091593, 2016–2020) and Senior Practitioner Fellowship (1104831, 2016– 2020). IES serves on the editorial boards of Neurology and Epileptic Disorders; may accrue future revenue on a pending patent report: therapeutic compound; has received speakers honoraria from Athena Diagnostics, UCB, GSK, Eisai and Transgenomics; has received scientific advisory board honoraria from Nutricia and GSK, has received funding for travel from Athena Diagnostics, UCB and GSK and receives/has received research support from the NHMRC, ARC, NIH, Health Research Council of New Zealand, March of Dimes, the Weizmann Institute, CURE, US Department of Defense and the Perpetual Charitable Trustees. Dr EY is supported by an NHMRC Early Career Fellowship (APP1073323).

    • Ethics approval Sydney Children’s Network and Westmead Hospital Human Ethics Committees (12/SCHN/395, SSA/13/WMEAD/53).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators Andrews PI (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia; School of Women’s and Children’s Health, University of New South Wales, Sydney, Australia), Barton JL (Brain and Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia), Burrow JNC (Royal Darwin Hospital, Northern Territory Medical Program, Darwin, Australia; Flinders University of South Australia, Adelaide, Australia), Butzkueven H (Department of Medicine, University of Melbourne, Melbourne, Australia), Cairns AG (Children’s Health Queensland, South Brisbane, Australia), Calvert S (Children’s Health Queensland, South Brisbane, Australia; Department of Neurosciences, Lady Cilento Children’s Hospital, South Brisbane, Australia), Caruana P (Department of Neurology, John Hunter Hospital, Newcastle, Australia; Hunter Medical Research Institute, Faculty of Medicine and Public Health, University of Newcastle, Newcastle, Australia), Chelakkadan S (Department of Neurosciences, Lady Cilento Children’s Hospital, South Brisbane, Australia), Clark D (Women and Children’s Hospital, Adelaide, Australia), Fraser CL (Save Sight Institute, University of Sydney, Sydney, Australia), Freeman JL (Department of Neurology, Royal Children’s Hospital, Melbourne, Australia; Neurosciences Research, Murdoch Children’s Research Institute and University of Melbourne, Melbourne, Australia), Gill D, Grattan-Smith PJ (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia), Gupta S (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia; University of Sydney, Sydney, Australia), Hardy TA (Brain and Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia), Kothur K (Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead; Sydney Medical School, University of Sydney, Sydney, Australia; TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia), Ling SR (Neurology Service, Department of Paediatric Medicine, KK Women’s and Children’s Hospital, Singapore), Lopez JA (Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead; Sydney Medical School, University of Sydney, Sydney, Australia), Malone S (Department of Neurosciences, Lady Cilento Children’s Hospital, South Brisbane, Australia), Marriott MP (Department of Neurology, Royal Melbourne Hospital; Eastern Health Clinical School, Monash University, Melbourne, Australia), Nosadini M (Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead; Sydney Medical School, University of Sydney, Sydney, Australia; Paediatric Neurology and Neurophysiology Unit, Department of Women’s and Children’s Health, University Hospital of Padua, Italy), O’Grady GL (Paediatric Neuroservices, Starship Children’s Health, Auckland District Health Board, Auckland, New Zealand), Orr CF (Department of Neurology, Royal Perth Hospital, Perth, Australia), Ouvrier R (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia; University of Sydney, Sydney, Australia), Parratt J (University of Sydney, Sydney, Australia; Department of Neurology, Royal North Shore Hospital, Sydney, Australia), Patrick E (School of Mathematics and Statistics and the Westmead Millenium Institute For Medical Research; The University of Sydney, Sydney, Australia), Pilli D (Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead; Sydney Medical School, University of Sydney, Sydney, Australia), Riminton DS (Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia), Riney K (Department of Neurosciences, Lady Cilento Children’s Hospital, South Brisbane, Australia; School of Medicine, University of Queensland, Brisbane, Australia), Rodriguez-Casero V (Department of Neurology, Royal Children’s Hospital, Melbourne, Australia; Monash Medical Centre, Melbourne, Australia), Ryan MM (Department of Neurology, Royal Children’s Hospital, Melbourne, Australia; Neurosciences Research, Murdoch Children’s Research Institute and University of Melbourne, Melbourne, Australia), Scheffer IE (University of Melbourne, Florey Institute, Austin Health, Melbourne, Australia), Shah UH (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia; Department of Neurosciences, Lady Cilento Children’s Hospital, South Brisbane, Australia), Shuey N (Neuro-ophthalmology clinic, Royal Victorian Eye and Ear Hospital and Department of Clinical Neurosciences, St Vincent’s Hospital, Melbourne, Australia), Spooner CG (Paediatric Neuroservices, Starship Children’s Health, Auckland District Health Board, Auckland, New Zealand), Subramanian GM (Department of Paediatrics, John Hunter Children’s Hospital, Newcastle, Australia), Tea F (Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead; Sydney Medical School, University of Sydney, Sydney, Australia), Thomas T (Neurology Service, Department of Paediatric Medicine, KK Women’s and Children’s Hospital, Singapore), Thompson J (Department of Neurology, St George Hospital, Sydney, Australia), Troedson C (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia), Ware TL (Department of Paediatrics, Royal Hobart Hospital, Hobart, Australia), Webster RI (TY Nelson Department of Neurology and Neurosurgery, Children’s Hospital at Westmead, Sydney, Australia; Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead, Sydney, Australia), Yiannikas C (University of Sydney, Sydney, Australia; Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia; Department of Neurology, Royal North Shore Hospital, Sydney, Australia), Yiu EM (Department of Neurology, Royal Children’s Hospital, Melbourne, Australia; Neurosciences Research, Murdoch Children’s Research Institute and University of Melbourne, Melbourne, Australia), Zou A (Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead; Sydney Medical School, University of Sydney, Sydney, Australia).

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