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July 08, 2014; 83 (2) Article

Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease

Russell C. Dale, Fabienne Brilot, Lisa V. Duffy, Marinka Twilt, Amy T. Waldman, Sona Narula, Eyal Muscal, Kumaran Deiva, Erik Andersen, Michael R. Eyre, Despina Eleftheriou, Paul A. Brogan, Rachel Kneen, Gulay Alper, Banu Anlar, Evangeline Wassmer, Kirsten Heineman, Cheryl Hemingway, Catherine J. Riney, Andrew Kornberg, Marc Tardieu, Amber Stocco, Brenda Banwell, Mark P. Gorman, Susanne M. Benseler, Ming Lim
First published June 11, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000570
Russell C. Dale
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Fabienne Brilot
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Lisa V. Duffy
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Marinka Twilt
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Amy T. Waldman
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Sona Narula
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Eyal Muscal
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Kumaran Deiva
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Erik Andersen
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Michael R. Eyre
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Despina Eleftheriou
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Paul A. Brogan
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Rachel Kneen
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Gulay Alper
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Banu Anlar
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Evangeline Wassmer
From the Neuroimmunology Group (R.C.D., F.B.), Children's Hospital at Westmead, University of Sydney, Australia; Boston Children's Hospital (L.V.D., M.P.G.), MA; the Division of Rheumatology (M.T., S.M.B.), The Hospital for Sick Children, University of Toronto, Canada; Children's Hospital of Philadelphia (A.T.W., S.N., B.B.), University of Pennsylvania; Paediatric Neurology and Rheumatology (E.M., A.S.), Texas Children's Hospital, Baylor College of Medicine, Houston; Assistance Publique-Hopitaux de Paris (K.D., M.T.), Hôpitaux Universitaires Paris-Sud, National Referral Center for Neuro-Inflammatory Diseases in Children, Pediatric Neurology Department and Université Paris-Sud, Inserm U1012, Le Kremlin-Bicêtre, France; Royal Children's Hospital Melbourne (E.A., A.K.), Australia; Great Ormond Street Hospital NHS Trust (M.R.E., C.H.), London; UCL Institute of Child Health (D.E., P.A.B.), London; Alder Hey Children's NHS Foundation Trust and the Institute of Infection and Global Health (R.K.), University of Liverpool, UK; Children's Hospital of Pittsburgh (G.A.), University of Pittsburgh, PA; Hacettepe University Child Neurology (B.A.), Turkey; Birmingham Children's Hospital (E.W.); John Radcliffe Hospital (K.H.), Oxford, UK; Neurosciences Unit and Mater Medical Research Institute (C.J.R.), Mater Children's Hospital, South Brisbane, University of Queensland, Australia; Alberta Children's Hospital (S.M.B.), Calgary, University of Calgary, Canada; and Evelina Children's Hospital (M.L.), London, UK.
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Kirsten Heineman
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Citation
Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease
Russell C. Dale, Fabienne Brilot, Lisa V. Duffy, Marinka Twilt, Amy T. Waldman, Sona Narula, Eyal Muscal, Kumaran Deiva, Erik Andersen, Michael R. Eyre, Despina Eleftheriou, Paul A. Brogan, Rachel Kneen, Gulay Alper, Banu Anlar, Evangeline Wassmer, Kirsten Heineman, Cheryl Hemingway, Catherine J. Riney, Andrew Kornberg, Marc Tardieu, Amber Stocco, Brenda Banwell, Mark P. Gorman, Susanne M. Benseler, Ming Lim
Neurology Jul 2014, 83 (2) 142-150; DOI: 10.1212/WNL.0000000000000570

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Abstract

Objective: To assess the utility and safety of rituximab in pediatric autoimmune and inflammatory disorders of the CNS.

Methods: Multicenter retrospective study.

Results: A total of 144 children and adolescents (median age 8 years, range 0.7–17; 103 female) with NMDA receptor (NMDAR) encephalitis (n = 39), opsoclonus myoclonus ataxia syndrome (n = 32), neuromyelitis optica spectrum disorders (n = 20), neuropsychiatric systemic lupus erythematosus (n = 18), and other neuroinflammatory disorders (n = 35) were studied. Rituximab was given after a median duration of disease of 0.5 years (range 0.05–9.5 years). Infusion adverse events were recorded in 18/144 (12.5%), including grade 4 (anaphylaxis) in 3. Eleven patients (7.6%) had an infectious adverse event (AE), including 2 with grade 5 (death) and 2 with grade 4 (disabling) infectious AE (median follow-up of 1.65 years [range 0.1–8.5]). No patients developed progressive multifocal leukoencephalopathy. A definite, probable, or possible benefit was reported in 125 of 144 (87%) patients. A total of 17.4% of patients had a modified Rankin Scale (mRS) score of 0–2 at rituximab initiation, compared to 73.9% at outcome. The change in mRS 0–2 was greater in patients given rituximab early in their disease course compared to those treated later.

Conclusion: While limited by the retrospective nature of this analysis, our data support an off-label use of rituximab, although the significant risk of infectious complications suggests rituximab should be restricted to disorders with significant morbidity and mortality.

Classification of evidence: This study provides Class IV evidence that in pediatric autoimmune and inflammatory CNS disorders, rituximab improves neurologic outcomes with a 7.6% risk of adverse infections.

GLOSSARY

AE=
adverse events;
CMV=
cytomegalovirus;
CTCAE=
Common Terminology Criteria for Adverse Events;
DoD=
duration of disease;
mRS=
modified Rankin Scale;
NMDAR=
NMDA receptor;
NMO=
neuromyelitis optica;
NMOSD=
neuromyelitis optica spectrum disorders;
OMAS=
opsoclonus myoclonus ataxia syndrome;
PML=
progressive multifocal leukoencephalopathy

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 111

  • Supplemental data at Neurology.org

  • Received October 15, 2013.
  • Accepted in final form February 11, 2014.
  • © 2014 American Academy of Neurology
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