The information below is based on the summary of product characteristics approved by regulatory authorities. For full details from the SmPC please click here: https://www.ema.europa.eu/en/documents/product-information/entyvio-epar-product-information_en.pdf

Additional related ECCO e-Learning resources can be found under IBD Curriculum Topic 6.1-6.11

Introduction and Mechanism of Action

Vedolizumab is a gut-selective immunosuppressive biologic. It is a humanised monoclonal antibody that binds specifically to the α4β7 integrin, which is preferentially expressed on gut homing T helper lymphocytes. By binding to α4β7 on certain lymphocytes, vedolizumab inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but not to vascular cell adhesion molecule-1 (VCAM-1). MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T lymphocytes to tissues within the gastrointestinal tract. Vedolizumab does not bind to, nor inhibit function of, the α4β1 and αEβ7 integrins. The α4β7 integrin is expressed on a discrete subset of memory T helper lymphocytes which preferentially migrate into the gastrointestinal tract and cause inflammation that is characteristic of ulcerative colitis and Crohn’s disease.

Therapeutic indications

Ulcerative colitis: Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

Crohn's disease: Vedolizumab is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

Dosing, administration

Ulcerative colitis: The recommended dose regimen of vedolizumab is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter. Therapy for patients with ulcerative colitis should be discontinued if no evidence of therapeutic benefit is observed by week 10. Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to 300 mg every four weeks.

Crohn's disease: The recommended dose regimen of vedolizumab is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter. Patients with Crohn’s disease, who have not shown a response may benefit from a dose of vedolizumab at week 10. Therapy should be continued every eight weeks from week 14 in responding patients. Therapy for patients with Crohn’s disease should be discontinued if no evidence of therapeutic benefit is observed by week 14.

Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to vedolizumab 300 mg every four weeks.

Contraindications

Hypersensitivity to the active substance or to any of the excipients

Active severe infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis, and opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML)

Adverse effects

The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory tract infection, bronchitis, influenza and sinusitis), headache, nausea, pyrexia, fatigue, cough, arthralgia

Infusion reactions (with symptoms such as dyspnoea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) have also been reported in patients treated with vedolizumab.

The following listing of adverse reactions is based on clinical trial and post-marketing experience and is displayed by system organ class. Within the system organ classes, adverse reactions are listed under headings of the following frequency categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Adverse Reactions

Infections and infestations

Laboratory parameters and Monitoring

Patients should be monitored for signs of infection.

The manufacturer advises monitoring for signs of progressive multifocal leucoencephalopathy although there is no evidence that there is an increased risk for this with vedolizumab

Interactions with other Drugs

Live vaccines should not be administered to patients receiving vedolizumab

There may be an increased risk of infection when used in combination with other drugs which suppress the immune system

Special situations

Pregnancy

There are limited amount of data from the use of vedolizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of vedolizumab during pregnancy unless the benefits clearly outweigh any potential risk.

Breast-feeding

Vedolizumab has been detected in human milk. The effect of vedolizumab on infants is unknown. The use of vedolizumab in lactating women should take into account the benefit of therapy to the mother and potential risks to the infant.