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Dig Dis Sci. 2018 Sep;63(9):2419-2429. doi: 10.1007/s10620-018-4924-8. Epub 2018 Jan 25.

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

Author information

1
Division of Gastroenterology, Virginia Mason Medical Center, Seattle, WA, 98101, USA.
2
Translational Program, Benaroya Research Institute at Virginia Mason Mailstop, IN-RC 1201 Ninth Avenue, Seattle, WA, 98101, USA.
3
Division of Gastroenterology, Virginia Mason Medical Center, Seattle, WA, 98101, USA. James.Lord@virginiamason.org.
4
Translational Program, Benaroya Research Institute at Virginia Mason Mailstop, IN-RC 1201 Ninth Avenue, Seattle, WA, 98101, USA. James.Lord@virginiamason.org.

Abstract

BACKGROUND/AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

KEYWORDS:

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

PMID:
29372476
DOI:
10.1007/s10620-018-4924-8
[Indexed for MEDLINE]

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