John J Chen1,2, Saif Huda3, Yael Hacohen4,5, Michael Levy6,7, Itay Lotan7,8, Adi Wilf-Yarkoni8, Hadas Stiebel-Kalish9,10, Mark A Hellmann8, Elias S Sotirchos6, Amanda D Henderson6,11, Sean J Pittock2,12,13, M Tariq Bhatti1,2, Eric R Eggenberger14,15,16, Marie Di Nome17,18, Ho Jin Kim19, Su-Hyun Kim19, Albert Saiz20,21, Friedemann Paul22,23,24,25, Russell C Dale26,27, Sudarshini Ramanathan26,28, Jacqueline Palace29, Valentina Camera29, Maria Isabel Leite29, Byron L Lam30, Jeffrey L Bennett31,32, Sara Mariotto33, Dave Hodge34, Bertrand Audoin35,36, Elisabeth Maillart37,38, Romain Deschamps39, Julie Pique40, Eoin P Flanagan2,12,13, Romain Marignier40. 1. Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. 2. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 3. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom. 4. Department of Neurology, Great Ormond Street Hospital for Children, London, United Kingdom. 5. Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom. 6. Department of Neurology, Johns Hopkins University, Baltimore, Maryland. 7. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. 8. Department of Neurology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 9. Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel. 10. Felsenstein Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 11. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 12. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 13. Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota. 14. Department of Neurology, Mayo Clinic, Jacksonville, Florida. 15. Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida. 16. Department of Neuro-Ophthalmology, Mayo Clinic, Jacksonville, Florida. 17. Department of Ophthalmology, Mayo Clinic, Scottsdale, Arizona. 18. Department of Neurology, Mayo Clinic, Scottsdale, Arizona. 19. Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea. 20. Service of Neurology, Hospital Clinic, University of Barcelona, Barcelona, Spain. 21. Neuroimmunology Program, Institut d'Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain. 22. NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. 23. Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. 24. Experimental and Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany. 25. Max Delbrueck Center for Molecular Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. 26. Translational Neuroimmunology Group, Kids Neuroscience Centre, Children's Hospital at Westmead, Sydney, Australia. 27. Department of Neurology, Children's Hospital at Westmead, Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia. 28. Department of Neurology, Concord Hospital, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia. 29. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. 30. Bascom Palmer Eye Institute, University of Miami, Miami, Florida. 31. Department of Neurology, Programs in Neuroscience and Immunology, University of Colorado School of Medicine, Aurora. 32. Department of Ophthalmology, Programs in Neuroscience and Immunology, University of Colorado School of Medicine, Aurora. 33. Neurology Unit, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 34. Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida. 35. Department of Neurology, University Hospital of Marseille, Marseille, France. 36. Aix-Marseille University, Center for Magnetic Resonance in Biology and Medicine, French National Centre for Scientific Research, Marseille, France. 37. Department of Neurology, Pitie-Salpetriere Hospital, Assistance Publique-Hȏpitaux de Paris, Paris, France. 38. Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Paris, France. 39. Lyon Civil Hospices, Department of Neurology, Neurologic and Neurosurgical Hospital Pierre Wertheimer, Bron, France. 40. Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Hȏpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France.
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.
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.
Authors: Elia Sechi; Laura Cacciaguerra; John J Chen; Sara Mariotto; Giulia Fadda; Alessandro Dinoto; A Sebastian Lopez-Chiriboga; Sean J Pittock; Eoin P Flanagan Journal: Front Neurol Date: 2022-06-17 Impact factor: 4.086