B-341 Analytical Performances of Homogeneous Mobility Shift Assay for Infliximab and Biosimilars and Resulting Exposure Assessments in Large Cohort of Patients With Inflammatory Bowel Diseases

Abstract Background Biosimilar for infliximab (IFX) are currently available for the treatment of various immune mediated inflammatory diseases including inflammatory bowel disease (IBD). We have validated the homogenous mobility shift assay (HMSA) for IFX biosimilars and describe exposure from a large population of patients with IBD treated with IFX and biosimilars. Methods Validation of the biosimilars, infliximab-dyyb (Inflectra®) and infliximab-abda (Renflexis®), was conducted in a reference clinical laboratory (Prometheus Laboratories, Inc.) for performance equivalence to the 1st international World Health Organization (WHO) IFX standard (16/170) by HMSA. The evaluated performance characteristics consisted of accuracy, precision, sensitivity, specificity, range, and linearity using spiked human serum. Following validation and implementation in the clinical laboratory, the drug median with interquartile range (IQR) and antibody to drug (ATI) prevalence and percentage relative to low-titer antibody cut-point of 10 U/mL (Am J Gastroenterol 2021;00:1-12), using de-identified patients, was evaluated by comparing treatment with IFX or the two validated biosimilars. Results The reportable range for the biosimilars was 0.98 μg/mL (precision: 5.5% CV; accuracy: 110.7% recovery) to 34 µg/mL (precision: 6.3% CV; accuracy: 105.4% recovery). Biosimilar intra-day, inter-day precision (CV) and accuracy (% recovery) across the reportable range were 3.8%, 3.6% and 105.1%, respectively. Furthermore, HMSA calibrated with IFX originator or biosimilar showed congruent results when compared to calibration with the WHO standard for the determination of drug concentrations using 20 clinical samples spanning the reportable range (Fig. 1). Median drug concentrations with IQR were 10.9 µg/mL (4.8–19.7 µg/mL) for infliximab originator, 9.8 µg/mL (3.9–18.1) for infliximab-dyyb, and 9.5 µg/mL (3.6–18.3) for infliximab-abda over a three-year period of testing, which also demonstrated similar ATI positivity rates. Conclusion HMSA is validated to be used as a tool for therapeutic drug monitoring (TDM) of patients treated with IFX originator and biosimilars.