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

Dale, Russell C., Brilot, Fabienne, Duffy, Lisa V., Twilt, Marinka, Waldman, Amy T., Narula, Sona, Muscal, Eyal, Deiva, Kumaran, Andersen, Erik, Eyre, Michael R., Eleftheriou, Despina, Brogan, Paul A., Kneen, Rachel, Alper, Gulay, Anlar, Banu, Wassmer, Evangeline, Heineman, Kirsten, Hemingway, Cheryl, Riney, Catherine J., Kornberg, Andrew, Tardieu, Marc, Stocco, Amber, Banwell, Brenda, Gorman, Mark P., Benseler, Susanne M. and Lim, Ming (2014) Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology, 83 2: 142-150. doi:10.1212/WNL.0000000000000570

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Author Dale, Russell C.
Brilot, Fabienne
Duffy, Lisa V.
Twilt, Marinka
Waldman, Amy T.
Narula, Sona
Muscal, Eyal
Deiva, Kumaran
Andersen, Erik
Eyre, Michael R.
Eleftheriou, Despina
Brogan, Paul A.
Kneen, Rachel
Alper, Gulay
Anlar, Banu
Wassmer, Evangeline
Heineman, Kirsten
Hemingway, Cheryl
Riney, Catherine J.
Kornberg, Andrew
Tardieu, Marc
Stocco, Amber
Banwell, Brenda
Gorman, Mark P.
Benseler, Susanne M.
Lim, Ming
Title Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease
Journal name Neurology   Check publisher's open access policy
ISSN 1526-632X
0028-3878
Publication date 2014-07-08
Sub-type Article (original research)
DOI 10.1212/WNL.0000000000000570
Open Access Status File (Publisher version)
Volume 83
Issue 2
Start page 142
End page 150
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams and Wilkins
Abstract To assess the utility and safety of rituximab in pediatric autoimmune and inflammatory disorders of the CNS.

Multicenter retrospective study.

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.

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.

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.
Formatted 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 inmRS 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 offlabel 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID K23 NS069806
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2015 Collection
 
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