Background: Etrolizumab is a gut-targeted anti-β7 monoclonal antibody targeting α4β7 and αEβ7 integrins. We aimed to compare the safety and efficacy of two doses of etrolizumab with placebo in patients with Crohn's disease.
Methods: BERGAMOT was a randomised, placebo-controlled, double-blind, phase 3 study done at 326 treatment centres worldwide.
Anti-integrins are therapeutically effective for inflammatory bowel disease, yet the relative contribution of α4β7 and αEβ7 to gut lymphocyte trafficking is not fully elucidated. Here, we evaluate the effect of α4β7 and αEβ7 blockade using a combination of murine models of gut trafficking and longitudinal gene expression analysis in etrolizumab-treated patients with Crohn's disease (CD). Dual blockade of α4β7 and αEβ7 reduces CD8 T cell accumulation in the gut to a greater extent than blockade of either integrin alone.
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