Expression and function of α4β7 integrin predict the success of vedolizumab treatment in inflammatory bowel disease

Inflammatory bowel diseases are medically intractable and require constant therapy in many cases. While a growing number of biologicals and small molecules is available for treatment, a substantial portion of patients experiences primary non-response to these compounds and head-to-head evidence for therapy selection is scarce. Thus, approaches to predict treatment success in individual patients are a huge unmet need.We had previously suggested that the expression and function of alpha 4 beta 7 integrin on T cells in the peripheral blood correlate to outcomes of therapy with the anti-alpha 4 beta 7 integrin antibody vedolizumab. Here, we conducted a translational multicenter trial to prospectively evaluate this hypothesis.In a cohort of 89 patients with inflammatory bowel disease undergoing regular therapy with vedolizumab, lower baseline expression of alpha 4 beta 7 was associated with short-term clinical response. Consistently, low alpha 4 beta 7 expression in patients achieving remission predicted sustained remission in week 30. Moreover, high dynamic adhesion of CD4+ T cells to MAdCAM-1 and high reduction of adhesion by vedolizumab in vitro at baseline were associated with clinical remission.These data substantiate the potential of alpha 4 beta 7 integrin function and expression to forecast outcomes of vedolizumab therapy. Further translational efforts are necessary to improve the performance of the assays and to implement the concept in clinical practice.