Clinical Utility of Next Generation Infliximab and Antibodies to Infliximab Assay

Abstract

Purpose: An assay to measure serum infliximab (IFX) and antibodies to infliximab (ATI) has been available since 2006 (Prometheus Laboratories, San Diego, CA). The first-generation enzymelinked immunosorbent assay (ELISA) could only measure ATI in the absence of IFX, due to IFX interference with the assay. A novel liquid-phase mobility shift assay was developed recently, allowing for measurement of IFX and ATI levels even when serum IFX is present (Anser IFX©, Prometheus Laboratories, San Diego, CA). The aim of this study is to investigate the clinical utility of this new test. Methods: We conducted a retrospective review of the electronic medical records of all inflammatory bowel disease (IBD) patients at our institution who underwent IFX/ATI testing between January 1, 2010 and December 31, 2012. The assay type, results, testing indication, and clinical management were obtained. Results: One hundred forty eight tests using ELISA assay and 57 tests using Anser IFX© assay were performed. Test results are summarized in Table 1. Fifty-two percent (77/148) of ELISA tests and 47% (27/57) of Anser IFX© tests were performed to evaluate inadequate/loss of response (LOR) to IFX. Overall, 48% (49/103) of patients experiencing LOR had therapeutic IFX levels. Using the ELISA assay, 11/31 patients (35%) with undetectable IFX levels were ATI-positive, as compared to 10/11 patients (91%) tested with the Anser IFX© assay. In addition, 2/13 (15%) of patients with subtherapeutic IFX concentrations using the Anser IFX© assay were ATI-positive (ATIs could not be measured in 41 patients with subtherapeutic IFX concentrations tested using the ELISA assay). In total, 12/24 patients (50%) with undetectable or subtherapeutic IFX concentrations, as measured by Anser IFX©, had detectable ATI, compared to 11/72 patients (15%) measured by ELISA assay.Table 1: Comparison of Anser IFX© versus ELISA assayConclusion: Use of mobility shift Anser IFX© assay is associated with a marked increase in proportion of patients with undetectable or subtherapeutic IFX concentrations who are found to be ATI-positive. These preliminary findings should be confirmed prospectively in a study with paired ELISA and Anser IFX© assays in the same patients. If confirmed, these findings suggest the Anser IFX© assay may explain the underlying reason (immunogenicity) for undetectable or subtherapeutic IFX concentrations in a larger proportion of patients. Disclosure - Dr. Sandborn - Consultant and Grant/Research Support: Janssen Biotech, Inc, Consultant: Prometheus Laboratories, Inc.; Dr. Levesque - Consultant: Prometheus Laboratories, Inc.