Clinical Experience with Measurement of Serum Infliximab and Antibodies to Infliximab Using a New Homogenous Mobility Shift Assay: Results of a Multi-center Observational Study

Abstract

Purpose: To characterize utilization of a new test for monitoring serum infliximab (IFX) and antibodies to infliximab (ATI) in Inflammatory Bowel Disease (IBD) patients on IFX therapy. The main advantage of this new test, using a liquid phase homogeneous assay, over the existing ELISA is that serum IFX does not interfere with quantification of ATI. Therefore, physicians can measure serum levels of IFX and ATI at any time during IFX therapy. Methods: IBD patients undergoing IFX therapy were enrolled in the study if their treating physician determined a need to measure IFX and ATI levels at any time during the course of therapy. Indications for the test, clinical status, and dosing information were collected at the time of blood draw. IFX and ATI levels were communicated to the physicians within 7 days and actions taken in response to the test results were documented. Results: As of this analysis, baseline data were available for 48 patients (28 CD, 19 UC and 1 indeterminate colitis). Mean age was 48y, mean BMI was 26.4 kg/m2 and mean duration of disease was 9.3 years. Forty-two percent of physicians ordered the test because their patients had an inadequate response or loss of response whereas 58% ordered the test in the absence of a lack or loss of response. Median IFX concentration was 9.45 μg/mL and 14 of 48 patients (29%) were positive for ATI. Among ATI-positive patients, 86% had IFX concentrations < 3 μg/mL, whereas only 9% of ATI-negative patients had IFX concentrations < 3 μg/mL (Odds Ratio = 0.02; p <<0.0001, Fisher's Exact test). Median IFX concentrations were 1 μg/mL and 20 μg/mL in ATI-positive and ATI-negative patients, respectively. Patients with lower disease scores had higher median IFX concentrations (median IFX = 9.3 μg/mL for HBI <7 vs. 5.2 μg/mL for HBI ≥7 in CD and median IFX = 34.00 μg/mL for partial Mayo score < 6 vs. 14.25 μg/mL for partial Mayo score ≥ 6 in UC). Changes made to the treatment regimen in response to knowing results of IFX/ATI testing included increasing the dose of IFX, changing the dosing interval, switching to another biologic, or performing additional work-up. Follow-up data for these patients will assess the clinical impact of adjusting therapy based on IFX / ATI levels. Conclusion: Results of this study are consistent with previous reports in the literature demonstrating that ATI development is negatively associated with serum IFX concentrations and clinical status. Physicians appear to find the measurement of serum IFX and ATI levels useful in multiple clinical scenarios including inadequate response or loss of response. Disclosure: Dr. Wolf: None Dr. Shringarpure: Employee of Prometheus Laboratories Inc. Dr. Lockton: Employee of Prometheus Laboratories Inc. Dr. Corey: None. Dr. Woods: None. Dr. Aguilar: None. Dr. Chuang: Employee of Prometheus Laboratories Inc. This research was supported by an industry grant from Prometheus Laboratories Inc.