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

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.

Clinical experiences and predictors of success of treatment with vedolizumab in IBD patients: a cohort study

“…E.g., baseline microbial signatures were associated with the success of treatment [ 20 ], while transcriptomic signatures failed to predict outcomes [ 35 ]. Our group had observed that dynamic adhesion of peripheral blood CD4 + T cells to MAdCAM-1 in vitro and early changes in the expression of α4β1 integrin on circulating CD4 + T cells correlate with clinical response [ 21 , 36 , 37 ].…”

“…While several potential biomarkers have been reported [19][20][21], such approaches require further validations before entering clinical practice. To the contrary, clinical characteristics of patients are easy to collect and may directly help to estimate outcomes.…”

Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

“…In ustekinumab clinical trials, the most common adverse reactions included nasopharyngitis, upper respiratory tract infection, and cough (Davies et al, 2019). Some drugs target the components of the transport pathway, such as MadCAM-1 targeting the adhesion molecules, and anti-α4β7, natalizumab, vedolizumab, and etrolizumab targeting anti-integrin (Moens et al, 2019;Allner et al, 2020). At present, various studies have proved that vedolizumab has good safety in the treatment of IBD, but the high price increases the burden on the patients (Yu et al, 2018a).…”

Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab Concentrations

“…This suggested mechanistic explanation for non-response is supported by a recent study where it was shown that more T cells from responders than from non-responders adhered to MAdCAM-1 prior to initiation of vedolizumab therapy. 24 In contrast, a study by Paul et al reported higher sMAdCAM-1 values in non-responders than in responders. 25 Nevertheless, the results of this study cannot be compared to our study because the patient population (primarily CD patients vs all UC patients), dosing regimen (dosage optimization vs no optimization) and sampling time point (maintenance vs. induction) are considerably different.…”