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

Background/Aims Vedolizumab is an anti-alpha 4 beta 7 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 alpha 4 beta 7 integrin on lymphocytes before and during vedolizumab therapy. Serum vedolizumab levels and alpha 4 beta 7 saturation were measured serially after induction. Results Fourteen out of 26 (54%) patients treated with vedolizumab responded to therapy. Pretreatment alpha 4 beta 7 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, log(10) serum vedolizumab levels at trough were higher in responders than nonresponders (p = .0007). Conversely, the percentage of effector memory T cells with free alpha 4 beta 7 at trough was lower in responders than nonresponders (p < .0001). However, loss of alpha 4 beta 7 saturation with vedolizumab was more sensitive to low serum vedolizumab in nonresponders. Conclusions Pretreatment alpha 4 beta 7 expression and alpha 4 beta 7 receptor saturation during maintenance therapy were identified as candidate biomarkers for vedolizumab response.