Multicenter Study

. 2014 Jul 8;83(2):142-50.

doi: 10.1212/WNL.0000000000000570. Epub 2014 Jun 11.

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

Russell C Dale¹, Fabienne Brilot², Lisa V Duffy², Marinka Twilt², Amy T Waldman², Sona Narula², Eyal Muscal², Kumaran Deiva², Erik Andersen², Michael R Eyre², Despina Eleftheriou², Paul A Brogan², Rachel Kneen², Gulay Alper², Banu Anlar², Evangeline Wassmer², Kirsten Heineman², Cheryl Hemingway², Catherine J Riney², Andrew Kornberg², Marc Tardieu², Amber Stocco², Brenda Banwell², Mark P Gorman², Susanne M Benseler², Ming Lim²

Affiliations

¹ 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. russell.dale@health.nsw.gov.au.
² 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.

PMID: 24920861
PMCID: PMC4117174
DOI: 10.1212/WNL.0000000000000570

Multicenter Study

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

Russell C Dale et al. Neurology. 2014.

. 2014 Jul 8;83(2):142-50.

doi: 10.1212/WNL.0000000000000570. Epub 2014 Jun 11.

Authors

Affiliations

¹ 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. russell.dale@health.nsw.gov.au.
² 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.

PMID: 24920861
PMCID: PMC4117174
DOI: 10.1212/WNL.0000000000000570

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.

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Figures

**Figure. Modified Rankin Scale score at initiation of rituximab and at outcome**
Modified Rankin Scale (mRS) score compared in all patients (total) and subgroups. (A) Groups are as follows (all patients n = 144 [total]): NMDAR encephalitis (NMDAR), opsoclonus myoclonus ataxia syndrome (OMAS), neuromyelitis optica spectrum disorders (NMOSD), neuropsychiatric systemic lupus erythematosus (NPSLE), and other groups (others). The follow-up was too short to create a mRS in 2 patients (one with OMAS, one other). mRS 0–2 infers a better outcome and is presented for each group as a percentage. The dotted line represents the change in mRS 0–2 between rituximab initiation and outcome. (B) mRS at rituximab initiation and outcome is compared according to the timing of rituximab administration. For each group, we separated an early and late group using the median duration of disease at rituximab initiation. Details of the timing, the median mRS, and the difference (Δ) in median mRS between initiation and outcome are also presented in table e-3.

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Comment in

B-cell depletion in children with neuroimmunologic conditions: the learning curve.
Chitnis T, Waubant E. Chitnis T, et al. Neurology. 2014 Jul 8;83(2):111-2. doi: 10.1212/WNL.0000000000000576. Epub 2014 Jun 11. Neurology. 2014. PMID: 24920852 No abstract available.

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials