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Anti-rituximab antibodies affect pharmacokinetics and pharmacodynamics of rituximab in children with immune-mediated diseases.

Authors :
Oomen I
Nassar-Sheikh Rashid A
Bouts AHM
Gouw SC
Kuijpers TW
Rispens T
de Vries A
Wolbink G
van den Berg JM
Schonenberg-Meinema D
Source :
Clinical and experimental rheumatology [Clin Exp Rheumatol] 2022 Jan; Vol. 40 (1), pp. 183-190. Date of Electronic Publication: 2021 Jun 26.
Publication Year :
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).<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
0392-856X
Volume :
40
Issue :
1
Database :
MEDLINE
Journal :
Clinical and experimental rheumatology
Publication Type :
Academic Journal
Accession number :
34251329
Full Text :
https://doi.org/10.55563/clinexprheumatol/ftira8