Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.

Abstract

Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin a4ß7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-a4) is approved for moderate to severe Crohn's disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-a4ß7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-ß7) blocks leukocyte trafficking via a4ß7 and cell adhesion via aEß7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-a4ß7 IgG2), PN-943 (orally administered and gut-restricted a4ß7 antagonist peptide), AJM300 (orally active small molecule inhibitor of a4), and ontamalimab (anti-MAdCAM-1 IgG).

View details for DOI 10.2147/CEG.S293272

View details for PubMedID 34466013

View details for PubMedCentralID PMC8402953