Vedolizumab 108mg/0.68ml solution for injection pre-filled disposable devices

Non-clinical studies have shown that the pharmacodynamic effects of vedolizumab are reversible upon removal of the antibody: pharmacologic activity of cells inhibited by vedolizumab could be partially restored within 24 hours after removal, with near complete restoration within 4 days. There are no known drug interactions as vedolizumab is a humanized antibody and does not modulate the production of cytokines, which is known to affect drug metabolism.[L48221]

The α4β7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is mainly expressed on gut endothelial cells and plays a critical role in homing T-lymphocytes to gut lymph tissue. The interaction of the α4β7 integrin with MAdCAM-1 has been implicated as an important contributor to chronic inflammation, a hallmark of ulcerative colitis and Crohn’s disease. Inhibition of α4β7 integrin by vedolizumab prevents the adhesion of lymphocytes to its natural ligand, thus decreasing the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue.[L48216]

In clinical trials with vedolizumab at doses ranging from 0.2 to 10 mg/kg (which includes doses outside of the recommended dose), saturation of α4β7 receptors on subsets of circulating lymphocytes involved in gut-immune surveillance was observed.[L48216]

In clinical trials with vedolizumab at doses ranging from 0.2 to 10 mg/kg and 180 to 750 mg (which include doses outside of the recommended dose) in healthy subjects and in patients with ulcerative colitis or Crohn’s disease, vedolizumab did not elevate neutrophils, basophils, eosinophils, B-helper and cytotoxic T-lymphocytes, total memory helper T-lymphocytes, monocytes or natural killer cells.[L48216]

A reduction in gastrointestinal inflammation was observed in rectal biopsy specimens from Phase 2 ulcerative colitis patients exposed to vedolizumab for four or six weeks compared to placebo control as assessed by histopathology.[L48216]

In a study of 14 healthy subjects, vedolizumab did not affect the CD4+ lymphocyte cell counts, CD8+ lymphocyte cell counts, or the CD4+:CD8+ ratios in the CSF.[L48216]