Comparison of Commercially Available Assays for Infliximab Concentrations and Antibodies to Infliximab With Assays Developed at Janssen and Used in Clinical Studies of Remicade®: Iinfliximab in IBD Patients Presidential Poster

Abstract

Introduction: Infliximab (IFX) concentrations and antibodies (Ab) to IFX (ATI) titers can be informative in assessing IBD response. In collaboration with KU Leuven, Sanquin, Dynacare and LabCorp, the accuracy and reliability of commercially available IFX and ATI assays were compared to assays used by Janssen for Remicade®(IFX) IBD studies. Methods: Samples were prepared by Janssen and shipped to labs. KU Leuven* and Dynacare used enzyme-linked immunosorbent assay (ELISA) to measure IFX and ATI. Sanquin used ELISA to measure IFX and a radioimmunoassay to measure ATI. LabCorp used electrochemiluminescence immunoassay (ECLIA) to measure IFX and ATI. Janssen used ELISA for IFX quantification, and ELISA (“old”) and ECLIA (“new”) for ATI assessments. Results:IFX Assays: Specificity: All assays were specific as they detected IFX, but not 5mg/mL of adalimumab, certolizumab pegol, golimumab or siltuximab. Selectivity: TNFa (0.5 - 50 ng/mL) did not interfere with IFX detection; ATI titers >10 interfered with IFX assessment. Accuracy: Confirmed by 3 independent measurements of IFX (0.125-20mg/mL) spiked sera from untreated IBD patients and with IFX measured in sera from IFX-treated IBD patients. Precision: IFX assays were precise, determined by inter-occasion reproducibility (2wks between assays; Dynacare assessed the same day). The correlation of Janssen IFX results to IFX results from Sanquin, Dynacare, KU Leuven, and LabCorp were 0.936, 0.945, 0.968 and 0.972, respectively. ATI assays: Specificity: Assays were specific in detecting anti-IFX Ab, and not affected by high titers of Ab against other monoclonal Ab drugs (ustekinumab and golimumab). Selectivity: Sanquin, LabCorp and new Janssen methods were drug tolerant (IFX >10ug/mL); ATI results from Dynacare and KU Leuven were affected by IFX concentrations at 2ug/mL or higher. Concentrations of free or bound TNFa (≤5ng/mL) did not interfere with ATI detection; a supraphysiologic TNFa concentration (50ng/mL) resulted in false positive results except Sanquin's. Precision: All assays were reproducible (2 wks between assays; Dynacare assessed samples same day). Conclusion: Results from all labs were similar and significantly correlated to the results of Janssen assays. These results may aid in interpretation of data from commercial assays and assays used in IBD clinical studies of Remicade (IFX).