Drug Levels and Antibodies Against TNF-blockers in Spondyloarthritis and Rheumatoid Arthritis are Associated with the Activity but they do Not Predict it

Abstract

Background: Many patients may have resistance to TNF-blockers. These drugs may induce neutralizing antibodies. The determination of the drug levels of TNF-blockers and Anti-Drug Antibodies (ADAs) against TNF-blockers may help to make clinical decisions. Objectives: The objective of this study was to associate and predict the drug levels of TNFblockers and ADAs in relation to disease activity in patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA). Methods: Cross-sectional study including patients fulfilling ASAS classification criteria for SpA and 2010 ACR-EULAR classification criteria for RA. These patients were treated with Adalimumab (ADA), Infliximab (IFX), and Etanercept (ETN). A bivariate analysis and the chi-square test were performed to evaluate the association of ADAs and drug levels with activity measures for SpA and RA. Five regression models analyzing drug levels, ADAs and disease activity measures using a multiple linear regression were performed in order to evaluate the prediction of ADAs and drug levels in relation to disease activity. Results: In SpA, IFX levels were associated with BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (p=0.034). In RA, total drug levels were associated with DAS28-ESR (28 joint Disease activity Score-erythrocyte sedimentation rate), (p=0.008), DAS28-CRP (p=0.042), CDAI (Clinical Disease Activity Index) (p=0.047) and SDAI (Simple Disease activity index), (p=0.017). ADA levels had association with CDAI (p=0.002) and SDAI (p=0.002). IFX levels were associated with a DAS28-ESR (p=0.044), DAS28-CRP (p=0.022) and SDAI (p=0.022). ADAs were associated in SpA with BASDAI (p=0.027). Drug levels and ADAs did not predict disease activity in patients with SpA or RA. Conclusions: ADAs and drug levels of anti-TNF are associated with disease activity measures in patients with SpA and RA. However, they cannot predict clinical activity in these conditions.

Applying precision medicine to unmet clinical needs in psoriatic disease

“…A number of studies have evaluated drug levels and ADAs in the inflammatory arthritides. In a 2019 study, drug levels and ADAs were associated with disease activity in spondyloarthritis and RA, but did not predict response to treatment [129]. Adalimumab drug levels and ADAs have also been associated with change in DAS28 and inversely correlated with HAQ in PsA, with drug levels influenced by BMI [130].…”

Seasoning to Perfection: How to Optimize Anti-TNF Therapy

“…Some studies suggest that therapy can be optimized by monitoring for the development of ADAbs, determining trough drug levels and/or measuring the bioactivity of the monoclonal antibody, 10 while other reports concluded that such monitoring rarely adds to therapeutic decision-making. 11,12 A related question is whether the addition of an anti-metabolite-like methotrexate to anti-TNF therapy could reduce the likelihood that neutralizing antibodies will develop. Such a strategy is plausible but must be weighed against the additional risk, cost, and inconvenience of a second immunosuppressive medication.…”