Rapid test detection of anti-infliximab antibodies: performance comparison with three different immunoassays

Abstract

Background and Aims: Therapeutic drug monitoring (TDM) of infliximab (IFX) and anti-infliximab antibodies (ATIs) is essential for treatment optimisation in inflammatory bowel disease (IBD) patients. The aim of this study was to estimate and compare the agreement and accuracy between a new rapid test and three established enzyme-linked immunosorbent assays (ELISAs) to quantify ATIs levels, and to evaluate the impact of exogenous IFX on the performance of these assays. Methods: We analysed 200 serum samples from 57 IBD outpatients in IFX induction or maintenance therapy at six IBD centres in Portugal. ATI levels were quantified using the rapid test Quantum Blue® (QB) Anti-Infliximab (Bühlmann) and three established ELISAs: In-House, Theradiag (Lisa Tracker Anti-Infliximab), and Immundiagnostik (IDKmonitor Infliximab). ATIs were quantified in patients’ serum samples and spiked samples with exogenous IFX, based on analytical and clinical cutoffs. Qualitative agreement and accuracy were estimated by Cohen’s kappa ( k) with 95% confidence intervals. Results: ATIs quantification with clinical cutoffs showed a slight agreement between QB rapid test and In-House [ k = 0.163 (0.051–0.276)] and Immundiagnostik [ k = 0.085 (0.000–0.177)]. Regarding IFX/ATIs status, the QB rapid test showed a substantial agreement with Theradiag [ k = 0.808 (0.729–0.888)] and a fair agreement with In-House [ k = 0.343 (0.254–0.431)] and Immundiagnostik [ k = 0.217 (0.138–0.297)]. The QB rapid test could not detect ATI-positive levels in samples with exogenous IFX at 5–300 µg/ml. Interference on ATIs detection was observed at exogenous IFX ⩾30 µg/ml for In-house and Immundiagnostik assays. Conclusion: QB rapid test is only suitable to detect ATI-positive levels in the absence of IFX.

Pharmacist-Driven Therapeutic Infliximab Monitoring at the Point of Care Using Rapidly Assessed Drug Levels in Patients with Inflammatory Bowel Disease

“…Third, patients with antidrug antibodies were excluded and their presence was not assessed during the study, although such an interaction with rapid tests has been previously reported. 36 Finally, for pragmatic reasons, the study did not examine the best way of implementing proactive drug level monitoring with at-infusion measurement of infliximab levels and did not explore changing infusion intervals but provided data on which such a question could be addressed.…”

Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives

“…32,145 However, as the number of such tests increases, their quality needs to be assessed and their accuracy compared with the commonly used laboratory measurements of drug concentrations and ADA to check for potential discrepancies. [146][147][148]…”

How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?—A prospective study

“…Serum CRP concentrations were determined using a highly sensitive assay (Konelab™, Thermo Scientific, Finland). FC and IFX levels were measured using the Quantum Blue ® fCAL and IFX quantitative assays, respectively (Bühlmann Laboratories, Switzerland), while anti‐IFX antibody levels were quantified with a validated in‐house ELISA (anti‐human lambda chain assay, 1.2–100 μg/mL; values below 1.7 μg/mL were considered negative) 10,11 . All determinations were performed in a central laboratory.…”