B-060 Measurement of Infliximab Clearance using a Bayesian Forecasting Tool and Impact of Albumin and Immunization Status During Maintenance Treatment of Inflammatory Bowel Disease

Abstract

Abstract Background Accelerated Clearance of monoclonal antibodies such as Infliximab (IFX) is a known predictive factor of pharmacokinetic origin that associates with poor outcome in patients with Inflammatory bowel diseases (IBD). We have implemented a Bayesian forecasting tool for IFX (PredictrPK® IFX) and calculated its Clearance. Our objective was to evaluate the impact of Albumin (ALB) and antibodies to IFX (ATI) on Clearance and exposure from patient specimens with IBD and submitted for testing in the routine clinical pharmacokinetic laboratory. Methods IFX concentration and ATI status were determined from serum using a homogenous mobility shift assay. Serum ALB concentration was determined using nephelometry. Clearance was estimated using inputted IFX concentration, ATI status, ALB, dose and interdose interval, and nonlinear mixed effect modeling with Bayesian priors. Patient specimens were collected anytime 20 days after the infusion and submitted for testing. Median Clearance (expressed as L/day) and estimated IFX trough concentrations by ATI status and lower Albumin levels (<4.0 g/dL) was calculated. Statistical analysis consisted of nonparametric Mann-Whitney tests. Results The prevalence of ATI was 9.1% in this cohort of patient specimens. Median Clearance was 0.246 L/day (IQR: 0.191–0.323 L/day) and median IFX Trough concentration was 11.9 µg/mL (IQR: 6.5–19.9 µg/mL). ATI status associated with lower IFX Trough concentrations and higher Clearance (P < 0.01). Lower ALB concentration regardless of ATI status also associated with lower IFX Trough concentrations (P < 0.01). There was twofold higher Clearance and twelvefold lower IFX Trough concentration in the presence of ATI and lower ALB. Results are presented in Table 1. Conclusion The data are consistent with the notion that IFX immunization and lower ALB impact Clearance and exposure to IFX.