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Detection of anti-drug antibodies using a bridging ELISA compared with radioimmunoassay in adalimumab-treated rheumatoid arthritis patients with random drug levels

Lookup NU author(s): Professor John IsaacsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objective. To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA.Methods. ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab-treated RA patients (159 samples). Immunogenicity concordance was determined using receiver operating characteristic curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (Delta DAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalized estimating equation.Results. Of the 60 RIA(+) samples (n = 31 patients), 19 (n = 10 patients) were also ELISA(+), corresponding to 31.7% of samples. Area under the curve for detecting ADAbs using ELISA (compared with RIA) using receiver operating characteristic curves was 0.65 (95% CI: 0.59, 0.71); this increased to 0.91 (95% CI: 0.81, 0.99) if ADAbs were a (c) 3/4100 AU/ml using RIA. In RIA(+)/ELISA(-) patients, adalimumab levels were associated with Delta DAS28 over 12 months [regression coefficient: 0.098 (95% CI: 0.043, 0.15), P < 0.0001] and while ADAbs were significantly associated with drug level, they were not directly associated with Delta DAS28 over 12 months [beta coefficient: 0.00083 (95% CI: -0.0038 to 0.0054), P = 0.72].Conclusion. ADAbs were detected using ELISA more frequently when present in high titres as measured by RIA. In RIA(+)/ELISA(-) patients, only drug levels were significantly associated with treatment response. Although ADAbs were not independently associated with treatment response, they may be helpful in determining the aetiology of low drug levels.

Publication metadata

Author(s): Jani M, Isaacs JD, Morgan AW, Wilson AG, Plant D, Hyrich KL, Chinoy H, Barton A

Publication type: Article

Publication status: Published

Journal: Rheumatology

Year: 2016

Volume: 55

Issue: 11

Pages: 2050-2055

Print publication date: 01/11/2016

Online publication date: 25/08/2016

Acceptance date: 11/07/2016

Date deposited: 06/01/2017

ISSN (print): 1462-0324

ISSN (electronic): 1462-0332

Publisher: Oxford University Press


DOI: 10.1093/rheumatology/kew299


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Funder referenceFunder name
Medical Evaluation Unit
National Institute for Health Research Biomedical Research Unit
North West England Medical Research Council
NIHR Manchester Musculoskeletal Biomedical Research Unit
20385Arthritis Research UK
20830Arthritis Research UK
G1000417/ 94909Medical Research Council
G1000417/94909Medical Research Council