Background Formation of antibodies (Ab) to TNFα blockers (adalimumab (ADA), etanercept (ETA) and infliximab (INF)) inversely correlates with functional drug levels and clinical outcome. Comparison of drug levels and anti-drug antibody (anti-drug Ab) monitoring is hampered by lack of standardization.
Objectives To determine the correlation and agreement between two different assays for measuring levels of TNFα blockers and anti-drug Ab.
Methods Serum samples of 145 patients with autoimmune rheumatic diseases were evaluated in two different assays developed by Sanquin (Amsterdam, Netherlands (Assay A), and a commercially available kit from Progenica Biopharma (Derio, Spain) (Assay B) performed in the Centre of Laboratory Medicine at Vilnius University Hospital Santariskiu clinics.
Results Assay A found detectable levels of ADA in 26 (96.3%), ETA – in 56 (88.9%), INF –in 35 (63.6%) patients, whereas Assay B these results were 26 (96.3%), 59 (93.7%) and 39 (70.9%), respectively. The good correlation was obtained when comparing Assay A vs. B in detecting drug levels (Spearman's rank correlation coefficient r=0.960, p<0.0001 for INF; r=0.932, p<0.0001 for ETA and r=0.765, p=0.001 for ADA). High agreement between two assays was found only in INF (ICC=0.925; 95% CI 0.875–0.956; p<0.0001)), but not in ADA (ICC=0.732; 95% CI 0.387–0.898; p<0.0001) and ETA assays (ICC=0.427; 95% CI 0.195–0.613; p<0.001).
The Bland–Altman and Mountain plots of ADA, INF and ETA show good agreement of two assays, used to analyze concentrations of all TNFα blockers (the best agreement found in INF group). Passing – Bablock regression revealed no systematic differences between the two assay methods in ADA, ETA and INF testing, although both methods has proportional differences.
Assay A detected anti-ADA Ab in 4 (14.8%), anti-INF Ab – in 17 (30.9%) patients. Assay B detected anti-ADA Ab in 1 (3.7%), anti-INF Ab – in 14 (25.4%) patients. Anti-ETA Ab were not detected by both assays.
Conclusions We found good correlation of TNFα blockers level measurements between the both commercially available assays. Nevertheless, the agreement between two assays could be calculated only for detection of TNFα blockers levels, but not for anti-drug Ab as the both assays report different outcome measures. The existing assays to measure levels of TNFα blockers and anti-drug Ab need to be standardized.
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Disclosure of Interest None declared