Association of Vedolizumab Concentrations Using Anser: Mobility Shift Assay and Clinical Response in IBD Patients in Clinical Practice

Abstract

Introduction: Availability of a drug-tolerant assay to measure serum Vedolizumab (VDZ) concentrations and antibodies to VDZ (ATV) titers is necessary for the optimal use of this drug in clinical practice. The aim of this study was to measure VDZ and ATV in serum using the VDZ mobility shift assay, and to assess the clinical utility of the VDZ assay. Methods: Longitudinal sera were obtained from 35 adult IBD patients (16 Crohn's Disease [CD] and 19 Ulcerative Colitis [UC]) at baseline before VDZ and at trough during induction. Clinical response was determined using physician's global assessment (PGA) and steroid-free status. VDZ and ATV concentrations were measured by homogeneous mobility shift assay (HMSA). TNFα (Singulex), C-reactive protein (CRP), and serum amyloid A (SAA) (MSD) were measured with commercial ELISAs. Linear regression analysis and Wilcoxon rank sum test were used to evaluate VDZ association with baseline biomarkers and compare differences in expression between groups, respectively. Results: The majority of patients had failed anti-TNF therapy (n=32) and were receiving steroids (n=28) at the time of VDZ initiation. A response to VDZ was seen in 80% (n=28) with complete resolution of symptoms in 37% (n=13). Median week 14 serum VDZ concentrations were higher in responders (R) compared to non-responders (NR) (12.3 vs. 7.1 μg/ml, p=0.02), and higher among patients who were steroid-free versus steroid dependent (12.5 vs. 7.8 μg/ml, p=0.03). Week 14 median SAA and TNFα concentrations were significantly lower in VDZ R versus NR (SAA: 5.3 vs. 17.7 mg/l, p=0.05; TNFα: 3.8 vs. 8.5 pg/ml, p=0.05), and serum VDZ were inversely associated with baseline SAA and TNFα (Adjusted R2: SAA=0.40, TNFα=0.49). ATV were detected in two patients during the induction phase at weeks 2 and 6 despite the presence of concomitant VDZ. Conclusion: A commercial grade, drug-tolerant VDZ assay was successfully utilized for therapeutic drug monitoring of VDZ and ATV concentrations in an anti-TNF refractory IBD population. ATV were detected as early as during the induction phase despite the presence of VDZ. Among patients achieving clinical response and steroid free-response or remission, the median serum VDZ concentration was ˜12 μg/ml, and VDZ concentrations correlated inversely with serum markers of inflammation. Validation in a larger cohort will be needed to determine the optimal serum VDZ concentrations for clinical response.