Paediatric Rheumatology
Pharmacodynamics of rituximab in paediatric immune mediated diseases: B cell depletion and repopulation, effects on immunoglobulin levels and risk for infections
A. Nassar-Sheikh rashid1, S.C. Bergkamp2, R.E. Kampinga3, S.C. Gouw4, A.H. Bouts5, M.J. Oosterveld6, P.A. Baars7, E.M. Van Leeuwen8, T.W. Kuijpers9, J.M. Van Den Berg10, D. Schonenberg-Meinema11
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam; and Department of Paediatrics, Zaans Medical Center, Zaandam, The Netherlands. a.nassar@amsterdamumc.nl
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Haematology, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Nephrology, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Nephrology, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam, The Netherlands.
CER16539
2023 Vol.41, N°11
PI 2323, PF 2330
Paediatric Rheumatology
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PMID: 37470239 [PubMed]
Received: 05/01/2023
Accepted : 24/05/2023
In Press: 13/07/2023
Published: 14/11/2023
Abstract
OBJECTIVES:
Rituximab (RTX), used for treatment in paediatric immune-mediated diseases, can lead to hypogammaglobulinaemia and thus to an increased risk of infection, but data on these adverse effects in children are scarce. We aimed to describe the pharmacodynamics of RTX by time to B cell repopulation in paediatric immune-mediated diseases and to assess whether low post-RTX immunoglobulin levels were associated with frequency and severity of infections.
METHODS:
Data of children with autoimmune diseases (AID), immune dysregulation (ID), haematological diseases (HD) and renal diseases (RD), including immunoglobulin levels pre-/post-RTX and occurrence of infections, who had received RTX at our centre were retrospectively collected. B cell depletion was defined as B cells <10 cells/μl.
RESULTS:
Post-RTX B cell depletion was achieved in 45/49 patients. In 30/45 patients with B cell repopulation, median time to repopulation was 166 days (IQR 140–224): AID group (n=9) (183 days (IQR 156–239), ID group (n=6) 170 days (IQR 128–184), HD group (n=7) 139 days (IQR 127–294), RD group (n=7) 160 days (IQR 121–367). Severe infections leading to hospitalisation occurred in 7/52 (13.5%) patients: ID (n=3), HD (n=1), RD (n=3). After RTX treatment, 13/52 patients (25%) had low IgG levels for their age at least once, 11/13 had an infection during low IgG but only 2/13 had a severe infection. Low IgG was not associated with severe infection (p=0.459).
CONCLUSIONS:
Time to B cell repopulation post-RTX ranged individually but did not significantly differ between paediatric patient groups. Severe infections were non-frequent and not associated with low (post-RTX) IgG levels.
