Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients

OBJECTIVE: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RESULTS: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results

Treatment of MOG antibody associated disorders: results of an international survey

PubMed: 32623595Introduction: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective: To survey the current global clinical practice of clinicians treating MOGAD. Method: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February–April 2019). Results: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ? 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ? 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). in children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.MedImmune Chugai Pharmaceutical Eden Hall Foundation, EHF Bundesministerium für Bildung und Forschung, BMBF Klaus Tschira Stiftung, KTS Roche Products Bundesministerium für Bildung und Forschung, BMBF Dietmar Hopp Stiftung 425331/2016-4 National Health and Medical Research Council, NHMRC Deutsche Forschungsgemeinschaft, DFG Medical Research Council, MRC Deutsche Forschungsgemeinschaft, DFG Novartis Deutsche Forschungsgemeinschaft, DFG Bayer Schering Japan Society for the Promotion of Science, KAKEN: KAKENHI 15K19472 17/2551-0001391-3 Dietmar Hopp Stiftung Shire Sanofi Genzyme Bayer Biogen Teva Pharmaceutical Industries National Institute for Health Research, NIHR Genzyme Alexion Pharmaceuticals Merck Guthy-Jackson Charitable Foundation Multiple Sclerosis Society, MS SocietyThe UK Neuromyelitis Optica Diagnostic and Advisory Service is funded by the Highly Specialised Commissioning Division of NHS England. There was no formal sponsorship for this study.D.H. Whittam, E.Gibbons, V. Karthikeayan, R. Kneen, S. Chandratre, J. de Seze, K. Deiva, R.Q. Hintzen, I. Kleiter, K. Rostasy, P. Huppke, F. Paul, A.K. Pröbstel, M.P. Amato, M. Nosadini, M.M. Mancardi, Z. Illes, A. Siva, G. Akman-Demir, L. Pandit, M. Apiwattankul, J.Y. Hor, S. Viswanathan, W. Qiu, H.J. Kim, I. Nakashima, R.C. Dale, M. Boggild, S. Broadley, M.A. Lana-Peixoto, P. Cabre, B.G. Weinshenker, B. Greenberg, M. Matiello, E.C. Klawiter, J.L. Bennett, A.I. Wallach, I. Kister, B.L. Banwell, D. Pohl, M.Levy, M.I. Leite, T. Solomon: nothing to disclose. O. Ciccarelli is a consultant for Roche, Novartis, Teva, Biogen and Merck. B Wildemann has received research grants and/or honoria from Merck Serono, Biogen, Teva, Novartis, Sanofi Genzyme, Bayer Healthcare, and research grants from Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, Dietmar Hopp Foundation and the Klaus Tschira Foundation. S. Jarius’s work was indirectly supported by research grants from Dietmar Hopp Stiftung and from Merck Serono. I.Kleiter has received speaker honoraria and travel funding from Bayer, Biogen, Novartis, Merck, Sanofi Genzyme, Roche; speaker honoraria from Mylan; travel funding from the Guthy-Jackson Charitable Foundation; consulted for Alexion, Bayer, Biogen, Celgene, Chugai, IQVIA, Novartis, Merck, Roche; and research support from Chugai, Diamed. B. Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, and Bayer AG; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon ?. O. Aktas reports grants from the German Research Foundation (DFG) and the German Ministry of Education and Research (BMBF), grants and personal fees from Bayer HealthCare, Biogen, Genzyme, Novartis, Teva and Viela Bio, and personal fees from Almirall, MedImmune, Merck Serono and Roche. G. Arrambide has received compensation for consulting services or participation in advisory boards from Sanofi, Merck, and Roche; research support from Novartis; travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS; and speaking honoraria from Sanofi, Merck, and Novartis. M. Tintore has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and Teva Pharmaceuticals. MT is co-editor of Multiple Sclerosis Journal-ETC. M. Capobianco received personal honoraria for speaking at meeting or participating in advisory boards from Biogen, Merck, Novartis, Roche, Sanofi, Teva. A. Altintas received travel grants and/or speaker honoraria from Merck, Generica and Novartis. H.J. Kim received research support from the Ministry of Science and ICT, Genzyme, Merck Serono, Teva-Handok, and UCB; received consultancy/speaker fees from Celltrion, Eisai, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and UCB; serves on a steering committee for MedImmune/VielaBio; is a co-editor for the Multiple Sclerosis Journal—Experimental, Translational, and Clinical, and an associated editor for the Journal of Clinical Neurology. K. Fujihara received consultancy/speaker fees: Alexion Pharmaceuticals, Chugai, Asahi Kasei Medical, Biogen, Eisai, Mitsubishi-Tanabe Pharma, Nihon, Novartis Pharmaceuticals, ONO Pharmaceutical, Takeda, and Teijin. S. Ramanathan has received an Early Career Fellowship from the National Health and Medical Research Council (Australia). D.K. Sato has received a Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI 15K19472); research support from CNPq/Brasil (425331/2016-4), FAPERGS/MS/CNPq/SESRS (17/2551-0001391-3) PPSUS/Brazil, TEVA (research grant for EMOCEMP Investigator Initiated Study), and Euroimmun AG (Neuroimmunological Complications associated with Arboviruses); and speaker honoraria from Biogen, Novartis, Genzyme, TEVA, Merck-Serono, Roche, and Bayer and has participated in advisory boards for Shire, Roche, TEVA, Merck-Serono and Quest/Athena Diagnostics. S. Tenembaum serves as a non-remunerated editorial board member of Neurology: Neuroimmunology & Neuroinflammation. She has received speaker and consulting fees from Biogen-Idec Argentina, Merck Serono LATAM, Genzyme-Sanofi, Novartis, and Teva Neuroscience during the last 3 years. D.M. Wingerchuk received grant support paid to Mayo Clinic from Alexion and TerumoBCT, consultant fees from MedImmune, Celgene, Novartis, and ONO Pharmaceuticals. A. Traboulsee: has received research funding from Chugai, Roche, and Sanofi Genzyme; received honoraria or travel support from Consortium of MS Centers, MS Society of Canada, Biogen, Teva, Roche, Merck/EMD Serono, Sanofi Genzyme, Chugai. J. Palace is partly funded by highly specialised services to run a national congenital myasthenia service and a neuromyelitis optica service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide ARGENX, UCB and Viela Bio and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide, MedImmune, Bayer Schering, Genzyme, Chugai and Alexion. She has received grants from the MS society, Guthrie Jackson Foundation, NIHR, Oxford Health Services Research Committee, EDEN, MRC, GMSI, John Fell and Myaware for research studies. R. Marignier serves on the scientific advisory board for Novartis and Medimmune; received speaker honoraria and travel funding from Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck. M. Lim has received consultation fees from CSL Behring; received travel grants from Merck Serono; and was awarded educational grants to organize meetings by Novartis, Biogen Idec, Merck Serono and Bayer. S. Huda has received research support from the Neuromyelitis Optica UK charity. A. Jacob served on the scientific advisory board for Shire Pharmaceuticals; received travel funding and/or speaker honoraria from Biogen Idec, Shire, and Terumo BCT; consulted for Shire Pharmaceuticals; and received research support from Biogen, Alexion Pharmaceuticals, NHS, and University of Liverpool

Treatment of MOG antibody associated disorders: results of an international survey

Introduction While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective To survey the current global clinical practice of clinicians treating MOGAD. Method Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February–April 2019). Results Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials

Treatment of MOG antibody associated disorders: results of an international survey

Introduction While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective To survey the current global clinical practice of clinicians treating MOGAD. Method Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). Results Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for >= 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after >= 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials

Treatment of MOG antibody associated disorders: results of an international survey

Introduction While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective To survey the current global clinical practice of clinicians treating MOGAD. Method Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). Results Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for >= 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after >= 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials