vedolizumab

MECHANISM: Vedolizumab binds the α4β7 integrin expressed on a subset of memory T lymphocytes that home to the gut. This prevents α4β7 from interacting with MAdCAM-1 (mucosal addressin cell adhesion molecule-1), which is expressed on intestinal endothelium (Peyer patches, lamina propria vessels). The result is blocked lymphocyte adhesion, transmigration, and infiltration into the GI mucosa. It does not block α4β1 binding to VCAM-1, so it does not affect CNS trafficking.

KEY COMPARISON WITH NATALIZUMAB: Natalizumab blocks both α4β1 and α4β7 (anti-α4 subunit). It is used in multiple sclerosis and Crohn disease, and it carries a risk of PML (JC virus reactivation). Vedolizumab is gut-selective (anti-α4β7 only), so it has essentially no increased PML risk and no significant systemic immunosuppression.

INDICATIONS: Moderate-to-severe ulcerative colitis and Crohn disease, usually after failure or intolerance of conventional therapy (corticosteroids, immunomodulators) or TNF-α inhibitors. It is given IV (induction at weeks 0, 2, and 6, then every 8 weeks). A subcutaneous maintenance formulation is also available.

ADVERSE EFFECTS: Nasopharyngitis, headache, arthralgia, and infusion reactions. Infections (especially upper respiratory) are possible, but the risk is lower than with systemic immunosuppressants. Rare hepatotoxicity has been reported.

CLINICAL PEARLS: - Onset is slow, and clinical response may take up to 10-14 weeks. - Screen for TB before starting therapy as with other biologics, though the risk is low. - It is often preferred in older patients or those with infection risk, because of its gut selectivity. - It is not effective for extraintestinal manifestations such as arthritis or spondylitis (the joint disease is not gut-restricted), unlike anti-TNF agents. - Anti-drug antibodies are uncommon. - Naming: "-mab" = monoclonal antibody, "-zu-" = humanized, "-li-" = immunomodulating target (older nomenclature).

IBD BIOLOGIC SNAPSHOT: Infliximab, adalimumab, and certolizumab target TNF-α. Ustekinumab targets IL-12/23 p40. Risankizumab and mirikizumab target IL-23 p19. Vedolizumab targets α4β7 integrin. Tofacitinib and upadacitinib are JAK inhibitors, and ozanimod is an S1P receptor modulator.