Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins

Recently, novel biologics or small molecular drugs have been introduced for overcoming the unmet needs associated with anti-tumor necrosis factor alpha agents for inflammtory bowel disease (IBD) treatment. Among these novel drugs, anti integrin agents block leukocyte trafficking to the intestine by blocking the interaction between integrin and cell adhesion molecules. Vedolizumab (anti-alpha 4137) is most widely used anti-integrin approved in both ulcerative colitis and Crohn's disease .It has been shown to be effective in both induction and maintenance therapy with a favorable safety profile due to gut selectivity. Several models incorporating clinical, genetic, immune and gut microbial markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-137) blocks leukocyte trafficking via alpha 4137 and cell adhesion via alpha E137 integrins. In addition, the introduction of subcutaneous vedolizumab showed similar efficacy and safety with improved patients' convenience. Other investigational anti-integrin therapies include abrilumab (anti-alpha 4137 IgG2), PN-943 (orally administered and gut-restricted alpha 4137 antagonist peptide), AJM300 (orally active small molecule inhibitor of alpha 4), and ontamalimab (anti-MAdCAM-1 IgG).