AB0318 Does Concentration of Antibodies To Etanercept and Adalimumab Correlates with Parameters of Disease Activity in Patients with Rheumatoid Arthritis?
Authors: J. Nedovic, B. Stamenkovic, S. Stojanovic, V. Zivkovic
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Introduction of tumor necrosis factor alpha (TNF) inhibitors has revolutionized therapy of rheumatoid arthritis (RA). Immunogenicity with consequent formation of antidrug antibodies (ADAb) is most responsible factor for secondary resistance. Adalimumab (ADA) as a fully humanized monoclonal antibody and Etanercept (ETN) as a fusion protein, are considered less immunogenic compared to other TNF inhibitors. In spite of this, various studies detected ADAb to ETN from 0% to 18% and for ADA from 0.04% to 87%. <h3>Objectives</h3> Our objectives were to determine the prevalence of ADAb to ETN and ADA in patients with RA and to evaluate correlations of ADAb with concentration of ETN and ADA and with parameters of disease activity. <h3>Methods</h3> Consecutive patients with established RA treated with ETN (25 patients) and ADA (20 patients) were enrolled in our cross-sectional study. Patients treated with ETN were older compared to patients treated with ADA (53.09±13.20 versus 47.06±12.54 years), had longer duration of disease (13.78±6.88 versus 9.11±6.91 years) and had longer duration of treatment (58.76±22.53 versus 20.3±14.11 years). Drug levels and concentration of ADAb were measured with commercially available ELISA kits from blood samples taken before next injection (trough values), and these levels were correlated with parameters of disease activity and compared between two groups. <h3>Results</h3> Both drugs had comparable efficacy according to DAS 28 SE (3.32±0.93 for ETN and 3.86±1.43 for ADA). Mean trough concentration of both drugs was satisfactory with values sevenfold greater than referent values: 240.23±502.64 ng/mL for ETN (referent values 0.0–35 ng/mL) and fourfold greater for ADA: 94.86±25.56 ng/mL (referent values 0.0–24.0 ng/mL). In spite of this, a more than a double concentration of ADAb was recorded in both groups: 326.96±292.51 IU/mL for ETN (referent values 0.0–142.06 IU/mL) and 23.21±56.87 IU/mL for ADA (referent values 0.0–10.00 IU/mL). Eight from 25 patients (32.4%) in ETN group and 8/20 (40%) in ADA group had elevated concentration of ADAb and this difference was not significant. Pearson correlation coefficient (r) showed weak negative correlation (r=-0.338) between concentration of ADAb to ETN and concentration of ETN and no correlation between ADAb to ADA and concentration of ADA. There were positive correlation of ADAb to ETN and Erythrocyte Sedimentation Rate (r=+0.482) and CRP (r=+0.411) but not with DAS 28 SE nor with the levels of RF and CCP Ab. The concentration of ADAb to ADA shoved only weak correlation with CCP Ab (r=+0.366) but not with any other parameter of disease activity. <h3>Conclusions</h3> Our data suggest that formation of ADAb after prolonged time of therapy is common even in the patients treated with TNF inhibitors considered as less immunogenic. But, a weak or even absent correlation with disease activity also suggest that not all of these ADAb are neutralizing with clinical consequences. These results also suggest that methodological aspects are of even more significance. There is a need for assay standardization and validation and consensus on the interpretation of serum drug and ADAb cut-off values with evidence based treatment algorithm useful for clinical practice. <h3>Disclosure of Interest</h3> None declared