John J Chen1, Eoin P Flanagan2, M Tariq Bhatti2, Jiraporn Jitprapaikulsan2, Divyanshu Dubey2, Alfonso Sebastian S Lopez Chiriboga2, James P Fryer2, Brian G Weinshenker2, Andrew McKeon2, Jan-Mendelt Tillema2, Vanda A Lennon2, Claudia F Lucchinetti2, Amy Kunchok2, Collin M McClelland2, Michael S Lee2, Jeffrey L Bennett2, Victoria S Pelak2, Gregory Van Stavern2, Ore-Ofe O Adesina2, Eric R Eggenberger2, Marie D Acierno2, Dean M Wingerchuk2, Byron L Lam2, Heather Moss2, Shannon Beres2, Aubrey L Gilbert2, Veeral Shah2, Grayson Armstrong2, Gena Heidary2, Dean M Cestari2, Hadas Stiebel-Kalish2, Sean J Pittock2. 1. From the Departments of Ophthalmology (J.J.C., M.T.B.), Neurology (J.J.C., E.P.F., M.T.B., J.J., D.D., A.S.L.C., B.G.W., A.M., J.-M.T., V.A.L., C.F.L., A.K., S.J.P.), Laboratory Medicine and Pathology (E.P.F., J.J., D.D, J.P.F., A.M., V.A.L., S.J.P.), and Immunology (V.A.L.) and Center for MS and Autoimmune Neurology (E.P.F., D.D., B.G.W., A.M., V.A.L., C.F.L., A.K., S.J.P.), Mayo Clinic, Rochester, MN; Department of Ophthalmology and Visual Neurosciences (C.M.M., M.S.L.), University of Minnesota, Minneapolis; Departments of Neurology and Ophthalmology (J.L.B., V.S.P.), University of Colorado Denver School of Medicine, Aurora; Departments of Ophthalmology and Visual Sciences and Neurology (G.V.S.), Washington University, St. Louis School of Medicine, MO; Departments of Ophthalmology and Visual Science and Neurology (O.-O.O.A.), McGovern Medical School, Houston, TX; Departments of Neurology, Neurosurgery, and Neuro-Ophthalmology (E.R.E.), Mayo Clinic, Jacksonville, FL; Departments of Ophthalmology (M.D.A.) and Neurology (D.M.W.), Mayo Clinic, Scottsdale, AZ; Bascom Palmer Eye Institute (B.L.L.), University of Miami, FL; Department of Neurology and Ophthalmology (H.M., S.B.), Stanford University, Palo Alto, CA; Neuro-Ophthalmology (A.L.G.), Kaiser Permanente, Northern California, Vallejo; Department of Ophthalmology (V.S.), Baylor College of Medicine/Texas Children's Hospital, Houston; Department of Ophthalmology (G.A., D.M.C.), Massachusetts Eye and Ear Infirmary/Harvard Medical School, Boston; Department of Ophthalmology (G.H.), Boston Children's Hospital, Harvard Medical School, MA; and Neuro-Ophthalmology Unit (H.S.-K.), Department of Ophthalmology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel. Chen.john@mayo.edu. 2. From the Departments of Ophthalmology (J.J.C., M.T.B.), Neurology (J.J.C., E.P.F., M.T.B., J.J., D.D., A.S.L.C., B.G.W., A.M., J.-M.T., V.A.L., C.F.L., A.K., S.J.P.), Laboratory Medicine and Pathology (E.P.F., J.J., D.D, J.P.F., A.M., V.A.L., S.J.P.), and Immunology (V.A.L.) and Center for MS and Autoimmune Neurology (E.P.F., D.D., B.G.W., A.M., V.A.L., C.F.L., A.K., S.J.P.), Mayo Clinic, Rochester, MN; Department of Ophthalmology and Visual Neurosciences (C.M.M., M.S.L.), University of Minnesota, Minneapolis; Departments of Neurology and Ophthalmology (J.L.B., V.S.P.), University of Colorado Denver School of Medicine, Aurora; Departments of Ophthalmology and Visual Sciences and Neurology (G.V.S.), Washington University, St. Louis School of Medicine, MO; Departments of Ophthalmology and Visual Science and Neurology (O.-O.O.A.), McGovern Medical School, Houston, TX; Departments of Neurology, Neurosurgery, and Neuro-Ophthalmology (E.R.E.), Mayo Clinic, Jacksonville, FL; Departments of Ophthalmology (M.D.A.) and Neurology (D.M.W.), Mayo Clinic, Scottsdale, AZ; Bascom Palmer Eye Institute (B.L.L.), University of Miami, FL; Department of Neurology and Ophthalmology (H.M., S.B.), Stanford University, Palo Alto, CA; Neuro-Ophthalmology (A.L.G.), Kaiser Permanente, Northern California, Vallejo; Department of Ophthalmology (V.S.), Baylor College of Medicine/Texas Children's Hospital, Houston; Department of Ophthalmology (G.A., D.M.C.), Massachusetts Eye and Ear Infirmary/Harvard Medical School, Boston; Department of Ophthalmology (G.H.), Boston Children's Hospital, Harvard Medical School, MA; and Neuro-Ophthalmology Unit (H.S.-K.), Department of Ophthalmology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel.
Abstract
OBJECTIVE: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. METHODS: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. RESULTS: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). CONCLUSION: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.
OBJECTIVE: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. METHODS: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. RESULTS: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). CONCLUSION: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.
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