Biological Therapy of Crohn’s Disease: Natalizumab, Vedolizumab, and Anti-MadCAM

Abstract

Intestinal inflammation is highly dependent on the recruitment of white blood cells out from the circulation to the mucosal immune system of the gut. Diapedesis and transmigration of activated lymphocytes to the site of inflammation is tightly regulated by a complex interaction between integrins on the leukocyte surface and cell adhesion molecules on microvascular endothelial cells of post-capillary venules (Fig. 36.1). Already in the early nineties, increased expression of vascular cell adhesion molecules was demonstrated in inflammatory bowel disease (IBD) [1–3]. This prompted investigation of anti-adhesion therapy as a therapeutic strategy in IBD. In 1993, Podolsky and coworkers showed that a monoclonal antibody targeting the leukocyte α4 integrin was effective in the treatment of colitis in the cotton-top tamarin [4]. Some years later, Hesterberg et al. found similarly beneficial effects in this model with an antibody against the gut-specific integrin dimer α4β7 [5]. These preclinical studies opened the gate for clinical pilot trials with anti-adhesion agents in IBD. Following a long developmental process, anti-adhesion molecules have now entered the therapeutic armamentarium of IBD. In this chapter, we summarize and discuss the evidence for the use of natalizumab, vedolizumab, and anti-MadCAM in CD.