Wincup, C;
Dunn, A;
Ruetsch-Chelli, C;
Manouchehrinia, A;
Kharlamova, N;
Naja, M;
Seitz-Polski, B;
... Jury, E; + view all
(2022)
Anti-rituximab antibodies demonstrate neutralising capacity, associate with lower circulating drug levels and earlier relapse in lupus.
Rheumatology
(In press).
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Abstract
OBJECTIVES: High rates of anti-drug antibodies (ADA) to rituximab have been demonstrated in patients undergoing treatment for SLE. However, little is known with regard to their long-term dynamics, impact on drug kinetics and subsequent implications for treatment response. In this study, we aimed to evaluate ADA persistence over time, impact on circulating drug levels, assess clinical outcomes and whether they are capable of neutralizing rituximab. METHODS: Patients with SLE undergoing treatment with rituximab were recruited to this study (n = 35). Serum samples were collected across a follow-up period of 36 months following treatment (n = 114). Clinical and laboratory data were collected pre-treatment and throughout follow-up. ADA were detected via electrochemiluminescent immunoassays. A complement dependent cytotoxicity assay was used to determine neutralizing capacity of ADA in a sub-cohort of positive samples (n = 38). RESULTS: ADA persisted over the 36-month study period in 64.3% of patients undergoing treatment and titres peaked earlier and remained higher in those who had previously been treated with rituximab when compared with than those who were previously treatment naive. ADA-positive samples had a significantly lower median drug level until six months post rituximab infusion (P = 0.0018). Patients with persistent ADA positivity showed a significant early improvement in disease activity followed by increased rates of relapse. In vitro analysis confirmed the neutralizing capacity of ADA to rituximab. CONCLUSIONS: ADA to rituximab were common and persisted over the 36-month period of this study. They associated with earlier drug elimination, an increased rate of relapse and demonstrated neutralizing capacity in vitro.
| Type: | Article |
|---|---|
| Title: | Anti-rituximab antibodies demonstrate neutralising capacity, associate with lower circulating drug levels and earlier relapse in lupus |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | https://academic.oup.com/rheumatology?login=true |
| Language: | English |
| Additional information: | © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | SLE, B cells, immunological techniques, biological therapy, autoantigens and autoantibodies |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158292 |
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