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

R. C. Dale; F. Brilot; L. V. Duffy; M. Twilt; A. T. Waldman; S. Narula; E. Muscal; K. Deiva; E. Andersen; M. R. Eyre; D. Eleftheriou; P. A. Brogan; R. Kneen; G. Alper; B. Anlar; E. Wassmer; K. Heineman; C. Hemingway; C. J. Riney; A. Kornberg; M. Tardieu; A. Stocco; B. Banwell; M. P. Gorman; S. M. Benseler; M. Lim

doi:10.1212/wnl.0000000000000570

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

R. C. Dale, F. Brilot, L. V. Duffy, M. Twilt, A. T. Waldman, S. Narula, E. Muscal, K. Deiva, E. Andersen, M. R. Eyre, D. Eleftheriou, P. A. Brogan, R. Kneen, G. Alper, B. Anlar, E. Wassmer, K. Heineman, C. Hemingway, C. J. Riney, A. KornbergM. Tardieu, A. Stocco, B. Banwell, M. P. Gorman, S. M. Benseler, M. Lim

Biomedical Engineering Department

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280 Citations (Scopus)

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 amedian 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.

Original language	English
Pages (from-to)	142-150
Number of pages	9
Journal	Neurology
Volume	83
Issue number	2
DOIs	https://doi.org/10.1212/wnl.0000000000000570
Publication status	Published - 8 Jul 2014

Keywords

B-CELL DEPLETION
MONOCLONAL-ANTIBODY THERAPY
NEUROMYELITIS-OPTICA
OPSOCLONUS-MYOCLONUS
MULTIPLE-SCLEROSIS
LYMPHOMA
TRIAL

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Dale, R. C., Brilot, F., Duffy, L. V., Twilt, M., Waldman, A. T., Narula, S., Muscal, E., Deiva, K., Andersen, E., Eyre, M. R., Eleftheriou, D., Brogan, P. A., Kneen, R., Alper, G., Anlar, B., Wassmer, E., Heineman, K., Hemingway, C., Riney, C. J., ... Lim, M. (2014). Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology, 83(2), 142-150. https://doi.org/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 amedian 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.",

keywords = "B-CELL DEPLETION, MONOCLONAL-ANTIBODY THERAPY, NEUROMYELITIS-OPTICA, OPSOCLONUS-MYOCLONUS, MULTIPLE-SCLEROSIS, LYMPHOMA, TRIAL",

author = "Dale, {R. C.} and F. Brilot and Duffy, {L. V.} and M. Twilt and Waldman, {A. T.} and S. Narula and E. Muscal and K. Deiva and E. Andersen and Eyre, {M. R.} and D. Eleftheriou and Brogan, {P. A.} and R. Kneen and G. Alper and B. Anlar and E. Wassmer and K. Heineman and C. Hemingway and Riney, {C. J.} and A. Kornberg and M. Tardieu and A. Stocco and B. Banwell and Gorman, {M. P.} and Benseler, {S. M.} and M. Lim",

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doi = "10.1212/wnl.0000000000000570",

language = "English",

volume = "83",

pages = "142--150",

journal = "Neurology",

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Dale, RC, Brilot, F, Duffy, LV, Twilt, M, Waldman, AT, Narula, S, Muscal, E, Deiva, K, Andersen, E, Eyre, MR, Eleftheriou, D, Brogan, PA, Kneen, R, Alper, G, Anlar, B, Wassmer, E, Heineman, K, Hemingway, C, Riney, CJ, Kornberg, A, Tardieu, M, Stocco, A, Banwell, B, Gorman, MP, Benseler, SM & Lim, M 2014, 'Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease', Neurology, vol. 83, no. 2, pp. 142-150. https://doi.org/10.1212/wnl.0000000000000570

TY - JOUR

T1 - Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease

AU - Dale, R. C.

AU - Brilot, F.

AU - Duffy, L. V.

AU - Twilt, M.

AU - Waldman, A. T.

AU - Narula, S.

AU - Muscal, E.

AU - Deiva, K.

AU - Andersen, E.

AU - Eyre, M. R.

AU - Eleftheriou, D.

AU - Brogan, P. A.

AU - Kneen, R.

AU - Alper, G.

AU - Anlar, B.

AU - Wassmer, E.

AU - Heineman, K.

AU - Hemingway, C.

AU - Riney, C. J.

AU - Kornberg, A.

AU - Tardieu, M.

AU - Stocco, A.

AU - Banwell, B.

AU - Gorman, M. P.

AU - Benseler, S. M.

AU - Lim, M.

PY - 2014/7/8

Y1 - 2014/7/8

N2 - 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 amedian 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.

AB - 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 amedian 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.

KW - B-CELL DEPLETION

KW - MONOCLONAL-ANTIBODY THERAPY

KW - NEUROMYELITIS-OPTICA

KW - OPSOCLONUS-MYOCLONUS

KW - MULTIPLE-SCLEROSIS

KW - LYMPHOMA

KW - TRIAL

U2 - 10.1212/wnl.0000000000000570

DO - 10.1212/wnl.0000000000000570

M3 - Article

SN - 0028-3878

VL - 83

SP - 142

EP - 150

JO - Neurology

JF - Neurology

IS - 2

ER -

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

Abstract

Keywords

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