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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-?4?7 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 ?4?1 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 ?4?1 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.

SUBMITTER: Allner C

PROVIDER: S-EPMC7158080 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Allner Clarissa C Melde Michaela M Becker Emily E Fuchs Friederike F Mühl Laura L Klenske Entcho E Müller Lisa L Morgenstern Nadine N Fietkau Konstantin K Hirschmann Simon S Atreya Raja R Atreya Imke I Neurath Markus F MF Zundler Sebastian S

BMC gastroenterology 20200415 1

<h4>Background</h4>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.<h4>Methods</h4>We performed a cohort study with 21 patients suffering from ulcerative colitis (UC), in which first-time treatment with vedolizumab was initiated. CD4<sup>+</sup> T ...[more]

PMID: 32293299

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Project description:Background and objectivesUlcerative colitis is highly prevalent in Canada and cost-effective ulcerative colitis therapies are warranted. Vedolizumab subcutaneous (SC) formulation was recently approved for ulcerative colitis maintenance therapy. We assessed vedolizumab SC cost effectiveness vs conventional and advanced therapeutics in patients with moderately to severely active ulcerative colitis from a Canadian public healthcare payer perspective.MethodsA hybrid decision tree/Markov model was developed to evaluate vedolizumab SC costs, quality-adjusted life-years, and cost effectiveness vs conventional therapy, adalimumab SC, infliximab intravenous, golimumab SC, tofacitinib, ustekinumab SC, and vedolizumab intravenous. This model predicts the number of patients achieving clinical response and remission after treatment induction, and sustained benefit during maintenance treatment. To account for statistical uncertainties, the base-case analysis was conducted in a probabilistic manner. Scenario analyses examined the impact of previous treatment with anti-tumor necrosis factor agents, dose escalation, loss of efficacy, and treatment adherence.ResultsIn the base-case analysis, conventional therapy was the most cost-effective therapeutic option in the overall population. Vedolizumab SC was cost effective and dominant compared with other advanced therapies (adalimumab, golimumab, infliximab, tofacitinib 5 mg, ustekinumab, and vedolizumab intravenous). The annual vedolizumab SC cost per patient was reduced vs ustekinumab SC, tofacitinib 5 mg, vedolizumab intravenous, and golimumab SC by $47,024, $3251, $2120, and $2004 (Canadian dollars), respectively, and exceeded that of infliximab, adalimumab, and conventional therapy by $582, $3293, and $41,024, respectively. Among the treatments, vedolizumab SC generated the highest quality-adjusted life-years overall (14.21), which translated into the best incremental cost per quality-adjusted life-years gained over conventional therapy in the overall population ($109,374) and in anti-tumor necrosis factor-naïve and anti-tumor necrosis factor-experienced patients ($41,658/$114,287).ConclusionsConventional therapy offered the most cost-effective therapeutic option followed by vedolizumab SC. Based on a $50,000/quality-adjusted life-year threshold, vedolizumab was cost effective in anti-tumor necrosis factor-naïve patients but not the overall population also when compared to conventional therapy.

Dataset Information

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

Publications

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

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