Paediatric Rheumatology
Anti-rituximab antibodies affect pharmacokinetics and pharmacodynamics of rituximab in children with immune-mediated diseases
I. Oomen1, A. Nassar-Sheikh rashid2, A.H. Bouts3, S.C. Gouw4, T.W. Kuijpers5, T. Rispens6, A. De Vries7, G. Wolbink8, J.M. Van Den Berg9, D. Schonenberg-Meinema10
- Department of Paediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands. i.oomen@amsterdamumc.nl
- Department of Paediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands.
- Department of Paediatric Nephrology, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands.
- Department of Paediatric Haematology, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands.
- Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
- Department of Biologics Laboratory, Bioanalysis, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
- Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, and Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands.
- Department of Paediatric Immunology, Rheumatology and Infectious diseases, Amsterdam University Medical Centers, Emma Children’s Hospital, Amsterdam, The Netherlands.
CER14547
2022 Vol.40, N°1
PI 0183, PF 0190
Paediatric Rheumatology
PMID: 34251329 [PubMed]
Received: 19/02/2021
Accepted : 07/05/2021
In Press: 26/06/2021
Published: 28/01/2022
Abstract
OBJECTIVES:
Rituximab (RTX) is a chimeric monoclonal CD20-antibody. Lack of efficacy has been suggested to be related to the presence of anti-drug antibodies (ADA). The aims of this study were to determine if ADA impact the pharmacokinetics (PK) and pharmacodynamics (PD) of RTX in children, whether the formation of ADA differs between various immune-mediated diseases and if it is related to the occurrence of infusion-related reactions (IRR).
METHODS:
All children <18 years who had received RTX treatment in our centre between December 2006 and February 2020 with known ADA/RTX-levels, were retrospectively included. The presence of ADA was defined as a titre >8 AU/ml.
RESULTS:
Of twenty-six children treated with RTX for various immune-mediated diseases, six patients were ADA-positive (23.1%). In all ADA-positive patients, RTX concentrations were undetectable in contrast to ADA-negative patients (median RTX concentration 3.1 μg/ml; IQR 0.57–12.0; p<0.001). Failure of B cell depletion was found in 5/6 ADA-positive and 1/19 ADA-negative patients (p=0.003). In SLE-patients, 50.0% (n=4/8) had developed RTX-ADA. Severe anaphylaxis (n=3) occurred only in the ADA-positive group.
CONCLUSIONS:
In our cohort of paediatric patients, undetectable RTX concentrations were found in ADA-positive patients, indicative that these ADA have a PK impact. RTX-ADA also seem to affect the PD, as in the majority of these patients, B cell depletion failed. ADA were most present in SLE-patients and anaphylactic reactions occurred only in ADA-positive patients. With this knowledge, a change of drug might be considered in the presence of RTX-ADA.
