Daniel H Whittam1, Alvaro Cobo-Calvo2, A Sebastian Lopez-Chiriboga3, Santiago Pardo4, Matthew Gornall5, Silvia Cicconi5, Alexander Brandt6, Klaus Berek7, Thomas Berger8, Ilijas Jelcic9, Grace Gombolay10, Luana Micheli Oliveira11, Dagoberto Callegaro11, Kimihiko Kaneko12, Tatsuro Misu12, Marco Capobianco13, Emily Gibbons14, Venkatraman Karthikeayan15, Bruno Brochet16, Bertrand Audoin17, Guillaume Mathey18, David Laplaud19, Eric Thouvenot20, Mikaël Cohen21, Ayman Tourbah22, Elisabeth Maillart23, Jonathan Ciron24, Romain Deschamps25, Damien Biotti26, Kevin Rostasy27, Rinze Neuteboom28, Cheryl Hemingway29, Rob Forsyth30, Marcelo Matiello4, Stewart Webb31, David Hunt32, Katy Murray32, Yael Hacohen33, Ming Lim34, M Isabel Leite35, Jacqueline Palace35, Tom Solomon14, Andreas Lutterotti9, Kazuo Fujihara12, Ichiro Nakashima36, Jeffrey L Bennett37, Lekha Pandit38, Tanuja Chitnis4, Brian G Weinshenker3, Brigitte Wildemann39, Douglas Kazutoshi Sato40, Su-Hyun Kim41, Saif Huda14, Ho Jin Kim41, Markus Reindl7, Michael Levy4, Sven Jarius39, Silvia Tenembaum42, Friedemann Paul6, Sean Pittock3, Romain Marignier2, Anu Jacob43. 1. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. Electronic address: daniel.whittam@nhs.net. 2. Pathologies de la Myéline et Neuro-inflammation, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, INSERM U1028, CNRS UMR 5292, Lyon 1 University, Center for Research in Neuroscience of Lyon, Lyon, France. 3. Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States. 4. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States. 5. Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, United Kingdom. 6. Experimental and Clinical Research Center Max Delbrueck Center for Molecular Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. 7. Medical University of Innsbruck, Innsbruck, Austria. 8. Department of Neurology, Medical University of Vienna, Vienna, Austria. 9. UniversitätsSpital Zürich, Zürich, Switzerland. 10. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States; Emory & Children's Pediatric Institute, Atlanta, Georgia, United States. 11. Hospital das Clinicas Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 12. Tohoku University Graduate School of Medicine, Sendai, Japan. 13. Neurology Dept. - Regional MS Centre, S. Luigi University Hospital, Orbassano, Italy. 14. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. 15. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom. 16. CHU de Bordeaux & INSERM U 1215, University of Bordeaux, Bordeaux, France. 17. Aix Marseille University, APHM, Hôpital de La Timone, Marseille, France. 18. Nancy University Hospital and Inserm CIC 1433, Nancy, France. 19. Nantes University Hospital, Nantes, France. 20. Hôpital Carémeau, Nimes University Hospital, Nimes, France. 21. Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France. 22. Reims University Hospital, University of Reims Champagne-Ardenne, Reims, LPN EA 2027, University of Paris VIII, Saint-Denis, France. 23. Pitié-Salpêtrière Hospital, APHP, Paris, France. 24. Poitiers University Hospital, Poitiers, France. 25. Fondation A. De Rothschild, Paris, France. 26. University Hospital of Purpan, Toulouse, France. 27. Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Witten, Germany. 28. Department of Paediatric Neurology, Erasmus MC-Sophia, Rotterdam, the Netherlands; Department of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, the Netherlands. 29. Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom. 30. Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom. 31. Department of Neurology, Queen Elizabeth University Hospital, Glasgow, United Kingdom. 32. Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, United Kingdom. 33. Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, United Kingdom; Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom. 34. Children's Neuroscience, Evelina London Children's Hospital @ Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. 35. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom. 36. Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan. 37. Departments of Neurology and Ophthalmology, Program in Neuroscience, University of Colorado School of Medicine, Aurora, Colorado, United States. 38. Nitte University, Mangaluru, Karnataka, India. 39. Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. 40. Hospital das Clinicas Faculty of Medicine, University of São Paulo, São Paulo, Brazil; Tohoku University Graduate School of Medicine, Sendai, Japan; Pontificia Universidade Catolica Rio Grande Do Sul, Porto Alegre RS, Brazil. 41. Research Institute and Hospital of National Cancer Center, Goyang, South Korea. 42. National Pediatric Hospital Dr. Juan P. Garrahan, Ciudad de Buenos Aires, Argentina. 43. Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom; Department of Neurology, The Cleveland Clinic Abu Dhabi, United Arab Emirates. Electronic address: anu.jacob@thewaltoncentre.nhs.uk.
Abstract
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.
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.
Authors: H L Pellkofer; M Krumbholz; A Berthele; B Hemmer; L A Gerdes; J Havla; R Bittner; M Canis; E Meinl; R Hohlfeld; T Kuempfel Journal: Neurology Date: 2011-04-12 Impact factor: 9.910
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Authors: John J Chen; Elias S Sotirchos; Amanda D Henderson; Eleni S Vasileiou; Eoin P Flanagan; M Tariq Bhatti; Sepideh Jamali; Eric R Eggenberger; Marie Dinome; Larry P Frohman; Anthony C Arnold; Laura Bonelli; Nicolas Seleme; Alvaro J Mejia-Vergara; Heather E Moss; Tanyatuth Padungkiatsagul; Hadas Stiebel-Kalish; Itay Lotan; Mark A Hellmann; Dave Hodge; Frederike Cosima Oertel; Friedemann Paul; Shiv Saidha; Peter A Calabresi; Sean J Pittock Journal: Mult Scler Relat Disord Date: 2022-01-11 Impact factor: 4.339
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