Baseline levels of dynamic CD4+ T cell adhesion to MAdCAM-1 correlate with clinical response to vedolizumab treatment in ulcerative colitis: a cohort study

Abstract

Abstract Background While the number of therapeutic options for treating inflammatory bowel diseases (IBD) is increasing, evidence for rational treatment decisions is scarce in many cases. In particular, appropriate biomarkers to predict the response to the anti-α4β7 integrin antibody vedolizumab are currently lacking. Methods We performed a cohort study with 21 patients suffering from ulcerative colitis (UC), in which first-time treatment with vedolizumab was initiated. CD4+ T cells were isolated from the peripheral blood and dynamic adhesion to recombinant mucosal vascular addressin cell adhesion molecule (MAdCAM-)1 in vitro as well as the effect of vedolizumab on such adhesion in vitro was determined. The expression of α4β1 integrin on peripheral blood CD4+ T cells was quantified by flow cytometry. Electronic patient records were reviewed to determine clinical response to vedolizumab. Results Dynamic adhesion of peripheral blood CD4+ T cells to MAdCAM-1 and the reduction of adhesion following vedolizumab treatment in vitro were higher and the change in α4β1 expression on CD4+ T cells was different in vedolizumab responders and non-responders. Responders could be identified with high specificity and positive-predictive value. Conclusions Determining dynamic adhesion of CD4+ T cells to MAdCAM-1 and the in vitro response to vedolizumab before treatment initiation or dynamic integrin regulation in the early course of treatment seem to be promising tools to predict the clinical response to vedolizumab therapy. Larger prospective studies are warranted.

Keywords

• Inflammatory bowel diseases
• T cells
• Vedolizumab
• Adhesion
• Gut homing