Vedolizumab: an α4β7 integrin antagonist for ulcerative colitis and Crohn’s disease

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted.

Advances in the development of new biologics in inflammatory bowel disease

“…Serious infections were identified in 5.5% of vedolizumab therapy patients compared with 3.0% of the patients under placebo. No cases of PML or malignancies were identified [ 28 - 31 ].…”

Understanding the Cautions and Contraindications of Immunomodulator and Biologic Therapies for Use in Inflammatory Bowel Disease

“…151,167 A recently published study by Colombel et al observed the long-term safety of VDZ across six trials, 2,830 patients with 4,811 person-years of follow-up, and in this population, if treated with NAT, six to seven cases of PML would have been expected. Again, when compared to placebo, there was no increased risk of any infection.…”

“…150 Anti-integrin monoclonal antibodies bind to the integrin, preventing its interaction with the inflamed mucosa, hence reducing the migration of effector lymphocytes into gut tissue, and reducing the inflammatory process. 151 …”

Vedolizumab therapy in pediatric inflammatory bowel disease – case report

“…As the most common adverse effects of vedolizumab were reported: nasopharyngitis, headache, arthralgia, and nausea. Longer-term safety trials are needed but based on evidence to date, there is no evidence of a higher odds of serious infections from the newly available biologic therapies, such as vedolizumab, compared to the anti-TNF agents (5) and also the progressive multifocal leukoencephalopathy (PML) associated with vedolizumab has not been reported (6).…”