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Multicenter Study
. 2022 May 1;79(5):518-525.
doi: 10.1001/jamaneurol.2022.0489.

Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

John J Chen  1   2 , Saif Huda  3 , Yael Hacohen  4   5 , Michael Levy  6   7 , Itay Lotan  7   8 , Adi Wilf-Yarkoni  8 , Hadas Stiebel-Kalish  9   10 , Mark A Hellmann  8 , Elias S Sotirchos  6 , Amanda D Henderson  6   11 , Sean J Pittock  2   12   13 , M Tariq Bhatti  1   2 , Eric R Eggenberger  14   15   16 , Marie Di Nome  17   18 , Ho Jin Kim  19 , Su-Hyun Kim  19 , Albert Saiz  20   21 , Friedemann Paul  22   23   24   25 , Russell C Dale  26   27 , Sudarshini Ramanathan  26   28 , Jacqueline Palace  29 , Valentina Camera  29 , Maria Isabel Leite  29 , Byron L Lam  30 , Jeffrey L Bennett  31   32 , Sara Mariotto  33 , Dave Hodge  34 , Bertrand Audoin  35   36 , Elisabeth Maillart  37   38 , Romain Deschamps  39 , Julie Pique  40 , Eoin P Flanagan  2   12   13 , Romain Marignier  40
Affiliations
Multicenter Study

Association of Maintenance Intravenous Immunoglobulin With Prevention of Relapse in Adult Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

John J Chen et al. JAMA Neurol. .

Abstract

Importance: Recent studies suggest that maintenance intravenous immunoglobulin (IVIG) may be an effective treatment to prevent relapses in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD); however, most of these studies had pediatric cohorts, and few studies have evaluated IVIG in adult patients.

Objective: To determine the association of maintenance IVIG with the prevention of disease relapse in a large adult cohort of patients with MOGAD.

Design, setting, and participants: This was a retrospective cohort study conducted from January 1, 2010, to October 31, 2021. Patients were recruited from 14 hospitals in 9 countries and were included in the analysis if they (1) had a history of 1 or more central nervous system demyelinating attacks consistent with MOGAD, (2) had MOG-IgG seropositivity tested by cell-based assay, and (3) were age 18 years or older when starting IVIG treatment. These patients were retrospectively evaluated for a history of maintenance IVIG treatment.

Exposures: Maintenance IVIG.

Main outcomes and measures: Relapse rates while receiving maintenance IVIG compared with before initiation of therapy.

Results: Of the 876 adult patients initially identified with MOGAD, 59 (median [range] age, 36 [18-69] years; 33 women [56%]) were treated with maintenance IVIG. IVIG was initiated as first-line immunotherapy in 15 patients (25%) and as second-line therapy in 37 patients (63%) owing to failure of prior immunotherapy and in 7 patients (12%) owing to intolerance to prior immunotherapy. The median (range) annualized relapse rate before IVIG treatment was 1.4 (0-6.1), compared with a median (range) annualized relapse rate while receiving IVIG of 0 (0-3) (t108 = 7.14; P < .001). Twenty patients (34%) had at least 1 relapse while receiving IVIG with a median (range) time to first relapse of 1 (0.03-4.8) years, and 17 patients (29%) were treated with concomitant maintenance immunotherapy. Only 5 of 29 patients (17%) who received 1 g/kg of IVIG every 4 weeks or more experienced disease relapse compared with 15 of 30 patients (50%) treated with lower or less frequent dosing (hazard ratio, 3.31; 95% CI, 1.19-9.09; P = .02). At final follow-up, 52 patients (88%) were still receiving maintenance IVIG with a median (range) duration of 1.7 (0.5-9.9) years of therapy. Seven of 59 patients (12%) discontinued IVIG therapy: 4 (57%) for inefficacy, 2 (29%) for adverse effects, and 1 (14%) for a trial not receiving therapy after a period of disease inactivity.

Conclusions and relevance: Results of this retrospective, multicenter, cohort study of adult patients with MOGAD suggest that maintenance IVIG was associated with a reduction in disease relapse. Less frequent and lower dosing of IVIG may be associated with treatment failure. Future prospective randomized clinical trials are warranted to confirm these findings.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Chen reported receiving consultant fees from UCB and Roche outside the submitted work. Dr Levy reported receiving personal fees from Alexion, Horizon, Genentech, UCB, and Mitsubishi Pharma and grants from Horizon, Alexion, Genentech, and UCB outside the submitted work. Dr Sotirchos reported serving on the advisory boards for Alexion, Viela Bio, and Genentech and receiving speaker fees from Viela Bio and Biogen. Dr H. Kim reported receiving a grant from the National Research Foundation of Korea and research support from Aprilbio and Eisai; consultancy/speaker fees from Alexion, Aprilbio, Biogen, Celltrion, Daewoong, Eisai, GC Pharma, HanAll BioPharma, Horizon Therapeutics (formerly Viela Bio), MDimune, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva-Handok, and UCB; and being a coeditor for the Multiple Sclerosis Journal and an associate editor for the Journal of Clinical Neurology. Dr Saiz reported receiving grants from Institut de Salud Carlos III Red Española de Esclerosis Múltiple during the conduct of the study; and consultancy/speaker fees from Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Alexion, and Janssen. Dr Ramanathan reported receiving grants from the National Health and Medical Research Council (Australia), the Petre Foundation (Australia), the Brain Foundation (Australia), the Royal Australasian College of Physicians, and the University of Sydney; being currently supported by a National Health and Medical Research Council Early Career Fellowship; being a consultant on an advisory board for UCB and Limbic Neurology; and receiving honoraria from Biogen and Limbic Neurology as an invited speaker. Dr Palace reported receiving support for scientific meetings and honoraria for advisory work from Merck Serono, Novartis, Chugai, Alexion, Roche, MedImmune, Argenx, UCB, Mitsubishi, Amplo, and Janssen; grants from Alexion, Chugai, MedImmune, and Amplo outside the submitted work; and being on the National Health Service England IVIG committee. Dr Bennett reported receiving consulting fees from Alexion, Chugai, Clene Nanomedicine, EMD Serono, AbbVie, Reistone Bio, Mitsubishi Tanabe, Genentech/Roche, and Viela Bio/Horizon; grants from Novartis, Mallinckrodt, and the National Institutes of Health; and having a patent for Aquaporumab issued. Dr Mariotto reported receiving speaker honoraria from Biogen and Novartis and research fundings from Euroimmun outside the submitted work. Dr Maillart reported receiving personal fees from Alexion, Biogen, Merck, Novartis, Roche, Sanofi, and Teva and grants from Biogen outside the submitted work. Dr Flanagan reported serving on advisory boards for Alexion, Genentech, and Horizon Therapeutics; receiving speaker honoraria from Pharmacy Times; receiving royalties from UpToDate; being a site primary investigator in a randomized clinical trial on Medi551 in neuromyelitis optica spectrum disorder run by MedImmune; receiving funding from the National Institutes of Health; being a member of the medical advisory board of the MOG project; and being an editorial board member of the Journal of the Neurological Sciences and Neuroimmunology Reports. Dr Pittock reported receiving grants and personal fees paid to Mayo Clinic; nonfinancial support from Alexion Pharmaceuticals Inc and MedImmune Inc/Viela Bio; personal fees from Genentech/Roche, UCB, and Astellas; holding patent 8,889,102 (application 12-678350) issued and patent 9,891,219B2 (application 12-573942) issued; and serving as a director of the Neuroimmunology Laboratory at Mayo Clinic. Dr Dale reported receiving 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); and honoraria from Biogen Idec as an invited speaker. Dr Leite reported receiving speaker honoraria or travel grants from Biogen Idec and Novartis; and serving on scientific or educational advisory boards for UCB, Argenx, and Viela Bio. Dr Deschamps reported receiving consulting fees from Alexion. Dr Marignier reported being a consultant for Alexion, UCB, Roche, and Viela Bio. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Estimates of Time to Relapse While Receiving Intravenous Immunoglobulin (IVIG)
Kaplan-Meier curves showing time to relapse for patients treated with maintenance IVIG, which is also separated into low-dose and high-dose IVIG.
See this image and copyright information in PMC

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