Medication Class Introduction

Anti-integrin medications, introduced in the 2000s, are a class of biologic drugs used in the treatment of inflammatory bowel disease (IBD) in appropriate patients.^1,2 They are monoclonal antibodies that bind to integrins on lymphocytes, blocking the leukocyte cells from migrating into the gastrointestinal tract.^2,3 Influx of immune cells such as lymphocytes into the gut mucosa contributes to the development of chronic inflammation seen in IBD.

Biosimilars are monoclonal antibodies that have highly similar clinical characteristics to an FDA-approved reference product.⁴ Anti-integrin biosimilar therapy is available in the US market.⁵

IBD Treatment Landscape^1,6–15

JAK=Janus kinase; S1P=sphingosine-1-phosphate; TNF=tumor necrosis factor.

Role in IBD Pathogenesis

Integrins, such as α₄β₁ and α₄β₇, are cell-surface transmembrane proteins on lymphocytes that bind to specific cell adhesion molecules, or CAMs, located on endothelial cell walls of intestinal blood vessels.^2,3,16 Key CAMs include mucosal addressin-cell adhesion molecule 1 (or MAdCAM-1) and vascular cell adhesion molecule 1 (or VCAM-1).²

These integrins facilitate lymphocyte migration from the bloodstream into intestinal tissue and are implicated in the pathogenesis of IBD.² IBD is associated with upregulation of both integrins and their corresponding cell adhesion molecules (CAMs), such as VCAM-1 and MAdCAM-1, in the intestinal tissue.

MAdCAM=mucosal addressin-cell adhesion molecule; VCAM=vascular cell adhesion molecule.

Mechanism of Action in IBD

Anti-integrin medications reduce inflammation in IBD by binding to specific integrins on lymphocytes, such as α₄β₁ and/or α₄β₇, thereby blocking their interactions with the endothelial cell adhesion molecules VCAM-1 and/or MAdCAM-1.^2,3,16 This restricts the migration of lymphocytes out of the blood vessels into the intestine, reducing inflammatory activity in the gut.²

MAdCAM=mucosal addressin-cell adhesion molecule; VCAM=vascular cell adhesion molecule.