Vedolizumab for the Treatment of IBD: A Selective Therapeutic Approach Targeting Pathogenic a4b7 Cells

Manol      Jovani; Silvio      Danese

Abstract

Inflammatory bowel diseases (IBD) are characterized by a persistent recruitment of large quantities of leucocytes from the blood to the gut mucosa. Adhesion molecules, such as integrins and their ligands, are the main players in this complex process. Leucocyte traffic control using a specific integrin inhibitors, such as natalizumab, has been plagued by severe systemic effects. The α₄β₇ – integrin and its ligand, the MadCAM-1, have been of special interest, since they are found exclusively on the gut-homing lymphocyte subpopulations and in the intestinal mucosa respectively. It follows that inhibition of such molecules should offer gut-specific immunosuppression, without the systemic effects of aspecific integrin- antagonists. We review the role of vedolizumab, a humanized antibody against the α₄β₇ – integrin, in both ulcerative colitis (UC) and Crohn's disease (CD). Results from clinical trials show that vedolizumab is effective in the induction and maintenance of remission in active CD and UC and has a very good safety profile. These data allow to confidently prospect that vedolizumab will be an important therapeutic option in the future of IBD treatment.

Keywords: Inflammatory bowel disease, Crohn’s disease, ulcerative colitis, α₄β₇ integrin, anti-integrins, adhesion molecules, natalizumab, vedolizumab, etrolizumab, MAdCAM-1, CAM.