Entyvio (Vedolizumab) Mechanism of Action and Side Effects
Vedolizumab (Entyvio) is a gut-selective integrin antagonist that prevents leukocyte migration into intestinal tissue by blocking α4β7 integrin, with a significantly lower risk of progressive multifocal leukoencephalopathy (PML) compared to natalizumab (Tysabri).
Mechanism of Action
- Vedolizumab is a humanized monoclonal antibody that selectively targets the α4β7 integrin heterodimer 1
- Unlike natalizumab which blocks both α4β1 and α4β7 integrins, vedolizumab specifically binds to α4β7 integrin expressed on the surface of leukocytes 1, 2
- This selective binding prevents the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) which is primarily expressed on gut endothelial cells 2
- By blocking this interaction, vedolizumab inhibits the migration of leukocytes across the endothelium into inflamed intestinal tissue, reducing inflammation in conditions like inflammatory bowel disease 1
- The gut-selective nature of vedolizumab's mechanism provides targeted immunosuppression that does not affect systemic immune responses to parenterally administered antigens 1
Side Effects
Common Side Effects
- Respiratory tract infections and nasopharyngitis are among the most common adverse events 1
- Headache is frequently reported in clinical trials 1
- Injection site reactions occur in approximately 5% of patients 1
- Arthralgia has been reported in 11.4% of patients in some studies 1
Serious Side Effects and Safety Profile
- Unlike natalizumab, vedolizumab has shown no confirmed cases of PML in long-term safety data 1
- Close monitoring for PML is still recommended due to the theoretical risk based on the mechanism of action, though this risk appears minimal 1
- Serious C. difficile infections, sepsis, or tuberculosis occurred in only 0.6% of patients in long-term safety studies 1
- Long-term safety data over 9 years has been reassuring with very small numbers of malignancies reported 1
Risk of Infections
- A meta-analysis of 49 studies showed that there is an increased risk of opportunistic infections with vedolizumab, similar to anti-TNF agents 1
- Vedolizumab is contraindicated in patients with active tuberculosis, sepsis, or opportunistic infections, including gut infections such as Clostridium difficile 1
- Pretreatment screening for infections (similar to anti-TNF protocols) is recommended before initiating therapy 1
- Latent tuberculosis should be treated prior to commencing vedolizumab 1
Special Considerations
- Patients should be up to date with vaccinations prior to starting treatment when possible 1
- Non-live vaccines may be administered during treatment, but live vaccines are contraindicated 1
- Treatment should be stopped if severe infection develops 1
- Vedolizumab affects the response to orally administered vaccines but does not alter immune response to parenterally administered antigens 1
Comparison with Natalizumab (Tysabri)
- Natalizumab has a broader mechanism of action, binding to both α4β1 and α4β7 integrins, affecting leukocyte migration throughout the body including the central nervous system 2
- The most significant safety concern with natalizumab is the risk of PML, a potentially fatal opportunistic brain infection caused by the JC virus 1
- The risk of PML with natalizumab increases with:
- Vedolizumab's gut-selective mechanism provides a more favorable safety profile regarding PML risk compared to natalizumab 1
Clinical Implications
- Vedolizumab is effective for inflammatory bowel disease treatment with a more favorable safety profile than natalizumab regarding PML risk 1
- Regular monitoring for infections and adverse events is still necessary with vedolizumab therapy 1
- For patients with extraintestinal manifestations of IBD, vedolizumab has shown efficacy in treating associated arthropathy and skin manifestations in some patients 1
- The choice between vedolizumab and other biologics should consider the patient's comorbidities, risk factors, and disease characteristics 1