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Original research
Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease
  1. Akash Virupakshaiah1,
  2. Vinicius A Schoeps1,
  3. Jonathan Race2,
  4. Michael Waltz2,
  5. Siefaddeen Sharayah3,
  6. Zahra Nasr1,
  7. Carson E Moseley1,
  8. Scott S Zamvil1,4,
  9. Cristina Gaudioso3,
  10. Allison Schuette2,
  11. Theron Charles Casper2,
  12. John Rose2,
  13. Eoin P Flanagan5,
  14. Moses Rodriguez5,
  15. Jan-Mendelt Tillema5,
  16. Tanuja Chitnis6,
  17. Mark P Gorman7,
  18. Jennifer S Graves8,
  19. Leslie A Benson7,
  20. Mary Rensel9,
  21. Aaron Abrams9,
  22. Lauren Krupp10,
  23. Timothy E Lotze11,
  24. Gregory Aaen12,
  25. Yolanda Wheeler13,
  26. Teri Schreiner14,
  27. Amy Waldman15,
  28. Janet Chong1,
  29. Soe Mar3,
  30. Emmanuelle Waubant1
  1. 1Neurology, UCSF Weill Institute for Neurosciences, San Francisco, California, USA
  2. 2The University of Utah, Salt Lake City, Utah, USA
  3. 3Department of Neurology, Washington University in St Louis, St Louis, Missouri, USA
  4. 4Program in Immunology, UCSF, San Francisco, California, USA
  5. 5Neurology, Mayo Clinic Rochester, Rochester, Minnesota, USA
  6. 6Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  7. 7Boston Children's Hospital, Boston, Massachusetts, USA
  8. 8Department of Neurology, University of California San Diego, La Jolla, California, USA
  9. 9Cleveland Clinic, Cleveland, Ohio, USA
  10. 10Pediatric MS Center, NYU Langone Health, New York, New York, USA
  11. 11Texas Children's Hospital, Houston, Texas, USA
  12. 12Loma Linda University Medical Center, Loma Linda, California, USA
  13. 13University of Alabama at Birmingham, Birmingham, Alabama, USA
  14. 14Children's Hospital Colorado, Aurora, Colorado, USA
  15. 15The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Akash Virupakshaiah, Neurology, UCSF, San Francisco, CA 94158, USA; akash.virupakshaiah{at}ucsf.edu

Abstract

Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.

Methods Prospectively collected data from paediatric patients with MOGAD seen by the US Network of Paediatric MS Centres were leveraged. Univariable and adjusted multivariable models were used to predict recurrent disease.

Results We identified 326 MOGAD cases (mean age at first event 8.9 years [SD 4.3], 57% female, 77% white and 74% non-Hispanic) and 46% relapsed during a mean follow-up of 3.9 years (SD 4.1). In the adjusted multivariable model, female sex (HR 1.66, 95% CI 1.17 to 2.36, p=0.004) and Hispanic/Latino ethnicity (HR 1.77, 95% CI 1.19 to 2.64, p=0.005) were associated with a higher risk of relapsing MOGAD. Maintenance treatment initiated before a second event with rituximab (HR 0.25, 95% CI 0.07 to 0.92, p=0.037) or intravenous immunoglobulin (IVIG) (HR 0.35, 95% CI 0.14 to 0.88, p=0.026) was associated with lower risk of a second event in multivariable analyses. Conversely, maintenance steroids were associated with a higher estimated relapse risk (HR 1.76, 95% CI 0.90 to 3.45, p=0.097).

Conclusion Sex and ethnicity are associated with relapsing MOGAD. Use of rituximab or IVIG therapy shortly after onset is associated with a lower risk of the second event. Preventive treatment after a first event could be considered for those with a higher relapse risk.

  • MULTIPLE SCLEROSIS
  • NEUROIMMUNOLOGY

Data availability statement

Data are available upon reasonable request. Participant data is securely stored electronically at the Data Coordinating and Access Center (DCAC) of the NPMSC registry, which is located at the University of Utah in Salt Lake City, United States. Anonymous raw data can be accessed upon reasonable request to the corresponding author, subject to approval from DCAC.

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Data availability statement

Data are available upon reasonable request. Participant data is securely stored electronically at the Data Coordinating and Access Center (DCAC) of the NPMSC registry, which is located at the University of Utah in Salt Lake City, United States. Anonymous raw data can be accessed upon reasonable request to the corresponding author, subject to approval from DCAC.

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Footnotes

  • SM and EW are joint senior authors.

  • X @tweetsatakash

  • SM and EW contributed equally.

  • Contributors Concept and design: AV, VAS, JR, MW, CMG, SM and EW. Acquisition, analysis, or interpretation of data: JR, MW, AS, TCC, AV, VAS, SM, and EW. Drafting of the manuscript: AV, VAS, SS, SM, and EW. Critical review of the manuscript for important intellectual content: all the authors. Obtained funding: TCC and EPF. Administrative, technical, or material support: JR, MW, AS, and TCC. Supervision: TCC, SM, and EW. AV is guarantor of the study.

  • Funding Infrastructural funding support for the project was provided by the NMSS (Grant # SI-210-38420, PI TCC). CEM is supported by a National Multiple Sclerosis Society Clinician Scientist Development Award (Grant # FAN-2107-38301). We acknowledge the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) funding allocated to EPF (Grant # 5R01NS113828-04), which supported MOG-IgG testing for participants in the NPMSC registry.

  • Competing interests AV is supported by Fellowship Grants from Biogen, EMD Serono and Novartis (2022-2024) and is a recipient of National Multiple Sclerosis Society (NMSS) Sylvia Lawry Fellowship Award (Grant#FP-2307-41848, 2024-2025).

    JR is supported by NMSS Grant SI-2110-38420, a grant awarded to the Utah DCAC which in turn provides funding for my contributions.

    CEM is supported by a National Multiple Sclerosis Society Clinician Scientist Development Award # FAN-2107-38301 and is listed on a patent application related to autoimmune aquaporinopathy.

    SSZ is supported by the National Institutes of Health (Grants 1 R01 AI131624-01A1 and 1 R01 AI170863-01A1), Race to Erase MS, The Sumaira Foundation and the Weill Institute of Neurosciences; received fees for consultation with Amgen/Horizon Therapeutics, Genentech, Genzyme and Merck; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen/Horizon Therapeutics, Genzyme and Merck and Co; received payments from Krakow for expert testimony; received support for attending meetings and/or travel from Horizon Therapeutics/Amgen, EMD Serono and Alexion; listed on a patent application related to autoimmune aquaporinopathy; participated on a Data Safety Monitoring Board or Advisory Board Horizon Therapeutics/Amgen, EMD Serono and Alexion; and serves in the leadership or fiduciary role in other boards, societies, committees or advocacy groups for NMSS, as deputy editor for Neurology, Neuroimmunology and Neuroinflammation, and ACTRIMS advisory committee.

    TCC has received research funding (for his institution) from NMSS Grant # SI-210-38420, Hoffmann-La Roche, Biogen and UCB.

    JR has research support from NMSS, NIH, Guthy Jackson Foundation, PCORI, Friends of MS, Biogen and VA.

    EPF is supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01NS113828) and funded this work; received research support from UCB; receives royalties for an article on UpToDate on MOGAD; a patent pending on DACH1-IgG as a biomarker of paraneoplastic autoimmunity; and participates on a Data Safety Monitoring Board or Advisory Board for Alexion, Horizon Therapeutics, UCB and Roche.

    J-MT serves as the site PI and collaborates with the NPMSC, which is supported by NMSS (SI-2110-38420, multisite funding: PI University of Utah, T.C. Casper), NINDS (R01NS117541) Institution (multisite funding; PI UCSF E. Waubant), NMSS (RG4861A3/1, multisite funding: PI University of Utah T.C. Casper) and NINDS (R01NS113828) Institution (PI Mayo Clinic E.P. Flanagan).

    TC is supported by grant funding from NIH, NMSS, Massachusetts Life Sciences Center, Department of Defense, Novartis Pharmaceuticals Corporation, Tiziana Therapeutics, Wesley Clover International, Genentech, Celgene Corp, Sumaira Foundation, Brainstorm Cell Therapeutics, Bristol Myers Squibb, EMD Serono, I-Mab Biopharma, Mallinckrodt ARD, Octave Bioscience, Sanofi and Genzyme; received consulting fees (payment made to the institution) from Genentech, Janssen Research & Development, Novartis Pharmaceuticals Corporation and Siemens Healthcare Diagnostics, Banner Life Sciences, Biogen, Bristol Myers Squibb, Octave Bioscience, Sandoz, Siemens, TG Therapeutics, UCB and Vida Ventures; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Genentech, MJH Life Sciences, Prime Education and Novartis Pharmaceuticals Corporation; and participates in on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb, Genentech, Novartis Pharmaceuticals Corporation, Octave Bioscience, Roche, Sanofi US Services.

    MPG serves as the site PI and collaborates with the NPMSC, which is supported by NMSS (SI-2110-38420, multisite funding: PI University of Utah, T.C. Casper), NINDS (R01NS117541) Institution (multisite funding; PI UCSF E. Waubant), NMSS (RG4861A3/1, multisite funding: PI University of Utah T.C. Casper) and NINDS (R01NS113828) Institution (PI Mayo Clinic E.P. Flanagan).

    JSG has received research funding from NMSS, the Department of Defence, Sanofi Pharmaceuticals, Octave Bioscience and EMD Serono.

    LAB has participated in multicenter clinical trials funded by Roche, Alexion and Biogen; received support from ROHHAD Fight, NIH and Rosamund Stone Zander Translational Neuroscience Center; received an honorarium for talks from Novartis; consultant to the National Vaccine Injury Compensation Program and the Massachusetts Department of Public Health; and received travel support from NMSS.

    MR has received research funding (Roche, Novartis, Biogen, Genentech, Connor B. Judge (CBJ) Foundation and National Multiple Sclerosis) and patient education funds (Genzyme, CBJ Foundation); served on the Data Safety Monitoring Committee (DSMC) for Biogen, Horizon, TG Theraeutics, Novartis, Cycle and EMD Serono; speaker or consultant for EMD Serono, Novartis, Genentech, Genzyme, Horizon, TG Therapeutics, Bristol Myers Squibb, (BMS), Cycle and Sanofi and is the Founder of Brain Fresh LLC and Co-Founder of Brain Ops Group; and involved in the leadership or fiduciary roles in other board, societies, committee or advocacy group for AAN, NMSS, Ohio Board Member.

    LK has received research funding from NMSS (#HC-1509-06233); additional research support was received from Novartis grant, NMSS grant #RG150705285, Biogen, NIH and Department of Defense; royalties received from various biopharmaceutical entities for use of the Fatigue Severity Scale; received consulting fees from Eisai, Gerson Lehrman, Peer View, WebMD/Medscape, F. Hoffman/LaRoche, CME Outfitters and General Dynamics Information; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bristol Myers Squibb and At the Limits; received payment for expert testimony from MCIC Vermont Individual; received travel support from Celgene; and participated on a Data Safety Monitoring Board or Advisory Board for Novartis and Biogen.

    GA has received research support from the NIH and NMSS.

    TS has received grants from the National MS Society, consulting fees from Hoffman LaRoche, honoraria from Cycle Pharmaceuticals, participated in a DSMB for Biogen and received travel support from AAN.

    SM is the site PI for clinical trials for paediatric MS, supported by Biogen and Roche.

    EW has not received any pharmaceutical company honorarium and is the site PI for Biogen, Alexion and Roche trials and is volunteering on a DSMB for a BMS trial; received funding from the NIH, the DoD and the Race to Erase MS; and received honoraria for talks for Advanced Curriculum and NeurologyLive.

    VAS, MW, SS, ZN, CMG, AS, AA, TEL, YW, AW and JC have no conflicts of interest to report.

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

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