S0874 Performance Characteristics of Homogenous Mobility Shift Assay Method Against World Health Organization International Standard for Infliximab Bioactivity and Impact of Dosing Regimens on Exposure

Abstract

INTRODUCTION: Therapeutic drug monitoring (TDM) of Infliximab remains an important clinical decision tool to improve outcomes in Inflammatory bowel diseases (IBD). However, one limitation of TDM in clinical gastroenterology practice is the lack of standardization across available technology platforms. Recently, the 1st international standard for infliximab (IFX) bioactivity was characterized and produced by World Health Organization (WHO). Our objective was to evaluate the performance characteristics of the Homogenous Mobility Shift assay (HMSA) against WHO calibration. METHODS: All IFX testing was conducted in a clinical laboratory accredited by the American College of Pathologists (Prometheus Biosciences, San Diego) using liquid chromatography size exclusion HMSA calibrated in house using IFX standards purchased independently from WHO. WHO Standard (NIBSC code: 16/170) was purchased as lyophilized powder, re-suspended to a final concentration of 50 µg/ml in normal healthy serum and stored at -80°C. IFX concentrations measured using in-house and WHO calibration methods were compared using de-identified specimens submitted for IFX testing. Data were analyzed using Deming’s regression and linear mixed effect models for repeated measures. IFX levels in relation to dosing intervals from patient specimens presenting with ICD-10 specific IBD codes were also evaluated. RESULTS: Between run (n = 6) precision was 9.5% (median CV; range 3.9–19.4%) and 8.6% (range: 5.2–17.8%) for 28 IFX specimens measured using in-house and WHO calibration, respectively. As presented in Figure 1, IFX levels measured using in-house calibration method (mean 13.8 ± 0.9 µg/ml) were comparable to those recovered from WHO calibration method (mean 13.9 ± 0.9 µg/ml) (Deming’s slope 1.00 CI 95%: 0.97–1.03). Linear mixed effect models also indicated comparable IFX levels between calibrations (slope = 0.986 ± 0.012; intercept = 0.11 ± 0.22; R2 = 0.97). Table 1 highlights IFX exposure levels in a total of 19,013 specimens submitted with dosing information between 2015 and 2020. A 5mg/Kg every 8 weeks dosing interval associated with 57% specimens above 5 µg/ml. Shorter intervals resulted in higher exposure. CONCLUSION: Our data indicate that IFX levels measured by HMSA in the reference laboratory yield comparable estimates to those from WHO. Calibration with WHO standards may facilitate harmonization of TDM in clinical gastroenterology practice.Figure 1Table 1