Pharmacodynamic assessment of vedolizumab for the treatment of ulcerative colitis

Abstract

Introduction Vedolizumab is an anti-integrin approved for the treatment of Crohn’s disease and ulcerative colitis. By binding the α4β7-integrin heterodimer, vedolizumab blocks leukocyte translocation into gastrointestinal tissue. Areas Covered This review discusses the chemistry, pharmacologic properties, clinical efficacy, and safety of vedolizumab in ulcerative colitis. Other medications available for the treatment of ulcerative colitis are also discussed. Expert Opinion Vedolizumab is a promising new agent for the treatment of ulcerative colitis. Its mechanism of action differs from TNF-α inhibitors and immune suppressants, allowing it to be used in cases of TNF-α inhibitor failure or non-response, or as a first-line biologic drug. Available safety data suggests that vedolizumab is not associated with an increased risk of infection or malignancy; however, additional post-marketing data are required to confirm these initial reports. Vedolizumab is likely to be used in growing numbers of patients over the coming years.

Comparison of the ELISA and ECL Assay for Vedolizumab Anti-drug Antibodies: Assessing the Impact on Pharmacokinetics and Safety Outcomes of the Phase 3 GEMINI Trials

“…Vedolizumab is a humanized recombinant monoclonal antibody that specifically binds to the α 4 β 7 integrin and prevents the recruitment of α 4 β 7 integrin leucocytes to the gut ( 2 ). Vedolizumab safety and efficacy are well established from multiple clinical ( 3 , 4 ) and real-world ( 5 ) studies, and it is approved for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) ( 6 – 9 ). Pivotal vedolizumab phase 3, randomized, placebo-controlled, double-blind studies included GEMINI 1 (NCT00783718) in UC and GEMINI 2 (NCT00783692) and 3 (NCT01224171) in CD ( 3 , 4 , 10 ).…”

Vedolizumab como terapia primaria en colitis ulcerosa y en la enfermedad de Crohn de moderada a grave: revisión y metaanálisis

“…Seis de los estudios seleccionados indican que más de la mitad de los pacientes con EII lograron la curación de la mucosa a los 12 meses 34 . Aunque los datos se limitaron a seis estudios, las tasas observadas de curación de la mucosa durante 12 meses fueron mayores que las tasas combinadas de remisión clínica, lo que respalda los informes anteriores de una falta de correlación clara entre las medidas de los síntomas clínicos y el daño intestinal evaluado por endoscopia [35][36][37] .…”

Vedolizumab-Induced Acute Interstitial Nephritis in Ulcerative Colitis

“… 1 The α4β7 integrin, a cell surface glycoprotein, is expressed on T cells and binds to mucosal addressin cell adhesion molecule-1. 7 By blocking α4β7, vedolizumab inhibits migration of memory and effector T cells as well as subsequent leukocyte extravasation to the affected gastrointestinal mucosa. 7 There are multiple integrins that play a critical role in the kidney; however, the role of α4β7 in kidney disease is unknown.…”

“…7 By blocking a4b7, vedolizumab inhibits migration of memory and effector T cells as well as subsequent leukocyte extravasation to the affected gastrointestinal mucosa. 7 There are multiple integrins that play a critical role in the kidney; however, the role of a4b7 in kidney disease is unknown. 8 Renal manifestations of IBD, such as nephrolithiasis, have been increasingly reported with the suggestion that they may be considered as an extraintestinal manifestation of the disease.…”