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Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease



Vedolizumab is an anti-α4β7 monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). This exploratory study aimed to identify biomarkers associated with vedolizumab response.


Twenty-six IBD patients (15 with Crohn’s, 11 with ulcerative or indeterminate colitis) initiating vedolizumab at a single center between 2014 and 2016 underwent sampling of serum and peripheral blood mononuclear cells (PBMCs) before and during vedolizumab therapy. Response was defined as steroid-free improvement in endoscopic score or Harvey–Bradshaw index/simple clinical colitis activity index (reduction greater than 3 or total less than 3). PBMCs were evaluated for immunophenotype and expression of α4β7 integrin on lymphocytes before and during vedolizumab therapy. Serum vedolizumab levels and α4β7 saturation were measured serially after induction.


Fourteen out of 26 (54%) patients treated with vedolizumab responded to therapy. Pretreatment α4β7 expression was higher in responders on multiple subsets of T, B, and NK cells, with terminal effector memory (p = .0009 for CD4 and .0043 for CD8) and NK cells (p = .0047) best discriminating between responders and nonresponders. During therapy, log10 serum vedolizumab levels at trough were higher in responders than nonresponders (p = .0007). Conversely, the percentage of effector memory T cells with free α4β7 at trough was lower in responders than nonresponders (p < .0001). However, loss of α4β7 saturation with vedolizumab was more sensitive to low serum vedolizumab in nonresponders.


Pretreatment α4β7 expression and α4β7 receptor saturation during maintenance therapy were identified as candidate biomarkers for vedolizumab response.

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Fig. 1
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Inflammatory bowel disease


Ulcerative colitis


Crohn’s disease


Indeterminate colitis


Mucosal addressin cell adhesion molecule


Peripheral blood mononuclear cell


Natural killer


Harvey–Bradshaw index


Simple clinical colitis activity index




Regulatory T cells


Half maximal inhibitory concentration


Interquartile range


Mean fluorescence intensity


T effector memory


Terminal effector memory T cells


Area under the curve


Thymically derived Treg


Peripherally derived Treg


Mucosal-associated invariant T cells


T follicular helper


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We would like to thank Kassidy Benoscek for subject consent, phlebotomy, and coordination, Katherine Schwedhelm with flow cytometer management, and Samuel Skinner for biostatistical review of the manuscript. This work was supported by a grant from the Digestive Disease Institute at Virginia Mason Medical Center.

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Correspondence to James D. Lord.

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JDL has received research funding from Takeda Pharmaceuticals for an alternative investigator-initiated project. MVC is a site principal investigator, and JDL and EKB are site sub-investigators for Takeda-funded clinical trials.

Author’s contribution

JDL contributed to study concept. EKB and JDL helped in study design. EKB, MVC, and JDL participated in clinical care and subject recruitment. EKB contributed to clinical data acquisition. DMS and JDL contributed to scientific data acquisition. EKB, DMS, and JDL involved in data analysis and interpretation. EKB and JDL drafted the manuscript and made critical revision for important intellectual content. All authors contributed to the critical revision of the manuscript and have read and approved the final version of this manuscript.

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Boden, E.K., Shows, D.M., Chiorean, M.V. et al. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease. Dig Dis Sci 63, 2419–2429 (2018).

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  • Anti-integrin
  • Biomarkers
  • Inflammatory bowel disease
  • Personalized medicine