Mechanism of Action of Entyvio (Vedolizumab)

Introduction

Entyvio (vedolizumab) is a recombinant humanized IgG1 monoclonal antibody that targets the α4β7 integrin on gut-homing T-lymphocytes. It is approved for moderate to severe ulcerative colitis and Crohn’s disease, particularly in patients who have not responded to or cannot tolerate TNF antagonists.

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Step-by-Step Mechanism of Action

1. Selective binding to α4β7 integrin
   Vedolizumab specifically binds to the α4β7 integrin on a subset of gut-homing T-cells, blocking their interaction with mucosal endothelial cells.
2. Prevention of lymphocyte trafficking to the gut
   By blocking α4β7 integrin binding to MAdCAM-1 on gut endothelial cells, it inhibits migration of inflammatory lymphocytes into intestinal tissue.
3. Gut-selective immune modulation
   This gut-specific action reduces inflammatory cell infiltration without broadly suppressing systemic immunity.
4. Reduced pro-inflammatory signaling
   Decreasing T-cell presence in the gut leads to lower activation of local inflammatory pathways, including NF-κB and MAPKs.
5. Amelioration of gut inflammation
   The net effect is reduced mucosal inflammation, improved histology, and symptomatic relief in inflammatory bowel disease.

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Pharmacokinetic Parameters

Parameter	Value
Route	Intravenous infusion (300 mg)
Bioavailability	100% (IV administration)
Half-life	~25 days
Distribution	~5 L (circulates in vascular compartment)
Metabolism	Proteolytic degradation
Excretion	No renal excretion; catabolized enzyme-dependently

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Clinical Uses

• Moderate to severe ulcerative colitis
• Moderate to severe Crohn’s disease
• Used when conventional therapies or TNF inhibitors fail or are contraindicated

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Adverse Effects

• Infusion-related reactions
• Increased risk of serious infections (e.g., nasopharyngitis, less systemic immunosuppression)
• Hepatic enzyme elevation
• Rare risk of progressive multifocal leukoencephalopathy (PML) with non-gut-specific integrin drugs—no confirmed cases with Entyvio

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Comparative Analysis

Agent	Target Mechanism	Selectivity	Common Uses
Vedolizumab	α4β7 integrin antagonist	Gut-selective	UC, Crohn’s
Natalizumab	α4β7 and α4β1 antagonist	Systemic	Crohn’s, MS (limited by PML risk)
TNF inhibitors	TNF-α neutralizing	Systemic	IBD, RA, PsA, psoriasis

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MCQs

1. Vedolizumab targets which integrin?
   a) α4β1 b) α4β7 c) αEβ7 d) β1 
   Answer: b) α4β7
2. By blocking α4β7, Entyvio prevents lymphocyte migration to:
   a) Skin b) Gut c) Brain d) Heart 
   Answer: b) Gut
3. This mechanism is considered:
   a) Systemic immunosuppression b) Gut-selective immunomodulation c) JAK inhibition d) TNF neutralization 
   Answer: b) Gut-selective immunomodulation
4. Primary downstream effect is reduced:
   a) IL-1 production b) NF‑κB activation c) JAK-STAT signaling d) COX-2 expression 
   Answer: b) NF‑κB activation
5. Typical half-life of vedolizumab is:
   a) 7 days b) 14 days c) 25 days d) 60 days 
   Answer: c) 25 days
6. Which route administers Entyvio?
   a) Oral b) IV infusion c) Subcutaneous injection d) Inhalation 
   Answer: b) IV infusion
7. Compared with natalizumab, vedolizumab has lower risk of:
   a) GI infection b) PML c) Allergy d) Joint pain 
   Answer: b) PML
8. Gut selectivity arises due to binding α4β7 and blocking:
   a) VCAM-1 b) ICAM-1 c) MAdCAM-1 d) E-selectin 
   Answer: c) MAdCAM-1
9. Common adverse effect:
   a) Severe neutropenia b) Infusion reaction c) Hypertension d) Hyperglycemia 
   Answer: b) Infusion reaction
10. Vedolizumab is NOT indicated for:
    a) Ulcerative colitis b) Crohn’s disease c) Rheumatoid arthritis d) TNF-refractory IBD 
    Answer: c) Rheumatoid arthritis

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FAQs

1. Why doesn’t Entyvio cause widespread immunosuppression?
Its α4β7 integrin targeting restricts its action to gut-homing lymphocytes, avoiding systemic immune compromise.

2. How often is vedolizumab given?
After initial doses at weeks 0, 2, and 6, maintenance infusions are administered every 8 weeks.

3. Is there a PML risk with Entyvio?
No confirmed PML cases—but natalizumab (which targets α4β1) carries this risk.

4. Can Entyvio be used during pregnancy?
Data are limited—use only if benefits outweigh potential risks; monitor closely.

5. How quickly does it work?
Some patients show improvement by 6 weeks; maximal response may take several months.

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References

• PubMed: Wyant et al. Vedolizumab mechanism of action overview (PMID: 27252400)
• DrugBank: Vedolizumab pharmacology summary
• Drugs.com: Entyvio MOA explanation
• Wikipedia: Vedolizumab entry (recently updated)
• PubMed Central: Vedolizumab blocks T-cell recruitment to gut