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Utility and safety of rituximab in pediatric autoimmune and inflamm… – PubMed – NCBI

Utility and safety of rituximab in pediatric autoimmune and inflamm… – PubMed – NCBI.

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

Dale RC1, Brilot F2, Duffy LV2, Twilt M2, Waldman AT2, Narula S2, Muscal E2, Deiva K2, Andersen E2, Eyre MR2, Eleftheriou D2, Brogan PA2, Kneen R2, Alper G2, Anlar B2, Wassmer E2, Heineman K2, Hemingway C2, Riney CJ2, Kornberg A2, Tardieu M2, Stocco A2, Banwell B2, Gorman MP2, Benseler SM2, Lim M2.

Author information

  • 1From 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.
  • 2From 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.

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.

© 2014 American Academy of Neurology

PMID:
24920861
[PubMed – indexed for MEDLINE]
PMCID:
PMC4117174

Free PMC Article