Anti-therapeutic antibodies and their clinical impact in patients treated with the TNF antagonist adalimumab. (August 2017)

• Record Type: Journal Article
• Authors: Cludts, Isabelle; Spinelli, Francesca Romana; Morello, Francesca; Hockley, Jason; Valesini, Guido; Wadhwa, Meenu
• Is Part Of: Cytokine. Volume 96(2017)
• Page Start: 16
• Page End: 23
• Publication Date: 2017-08
• Subjects: AS ankylosing spondylitis -- ATA anti-therapeutic antibodies -- BASDAI Bath Ankylosing Spondylitis Disease Activity Index -- DAS28 Disease Activity Score 28 -- DMARDs disease-modifying antirheumatic drugs -- ECL electrochemiluminescence -- LoD limit of detection -- nhs normal human serum/sera -- PC positive control -- PsA psoriatic arthritis -- RF rheumatoid factors -- RA rheumatoid arthritis -- SpA spondyloarthritis; Immunogenicity -- Adalimumab trough levels -- Electrochemiluminescence assay -- TNF antagonist -- Neutralizing antibodies; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2017.02.015
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: ECL-based assays for measurement of adalimumab and adalimumab antibodies. Performance of ECL antibody assay not significantly improved by acid dissociation. Negative correlation between levels of antibody and free adalimumab. Negative correlation between adalimumab level and disease activity scores. Abstract: Patients treated with the TNF antagonist adalimumab develop anti-therapeutic antibodies (ATA), the prevalence of which varies depending on the assay used. Most assays are compromised due to the presence of adalimumab in the clinical samples. Our objective was to develop an antibody assay, applicable for clinical testing, which overcomes the limitation of therapeutic interference and to further determine the relationship between ATA development, adalimumab levels and disease activity in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS). Use of an electrochemiluminescence platform permitted development of fit-for-purpose immunoassays. Serum samples from patients, taken prior to and at 12 and 24 weeks of treatment, were retrospectively analysed for levels of adalimumab and ATA. Overall, the antibody prevalence was 43.6% at 12 weeks and 41% at 24 weeks of treatment. Disruption of immune complexes by acid dissociation, a strategy often adopted for this purpose, only marginally increased the antibody prevalence to 48.7% and 46% at 12 and 24 weeks respectively. We found that antibody formation was associated with decreasing levels of circulating adalimumab, but no direct effect on disease activity was evident as assessed using DAS28 for RA patients and BASDAI for PsA and AS patients. However, a negative correlation of free adalimumab trough levels with disease activity scores was observed. Data showed that adalimumab levels can serve as an indicator of ATA development which can then be confirmed by ATA testing. Monitoring of both therapeutic and antibodies should be considered during adalimumab therapy to allow clinicians to personalise treatments for maximal therapeutic outcomes.