Mechanism of action of Vedolizumab

Mechanism of Action of Vedolizumab (Entyvio)

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Introduction

Vedolizumab is a humanized IgG1 monoclonal antibody used for the treatment of moderate to severe ulcerative colitis and Crohn’s disease. It selectively targets the gastrointestinal immune system, offering gut-specific immunomodulation with minimal systemic immunosuppression.

Step-by-Step Mechanism of Action

  1. Targeting α4β7 Integrin
    Vedolizumab binds specifically to the α4β7 integrin, a cell adhesion molecule found on a subset of T lymphocytes.
  2. Blocking MAdCAM-1 Interaction
    This binding prevents α4β7 integrin from interacting with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is selectively expressed on gut endothelial cells.
  3. Inhibition of Lymphocyte Trafficking
    By disrupting this interaction, vedolizumab blocks the migration of memory T-cells into inflamed gut tissue.
  4. Localized Immune Suppression
    The drug’s action is largely confined to the gastrointestinal tract, sparing systemic immunity and reducing the risk of systemic infections.
  5. Reduction in Inflammatory Response
    This results in decreased cytokine production, reduced mucosal damage, and improved histological healing in inflammatory bowel disease.
Mechanism of action of Vedolizumab flowchart
Vedolizumab mechanism of action flowchart

Pharmacokinetic Parameters

ParameterValue
RouteIntravenous infusion
BioavailabilityNot applicable (IV administration)
Half-life~25.5 days
Volume of distribution~5 L
MetabolismProteolytic degradation
ExcretionNon-renal; catabolized into peptides

Clinical Uses

  • Moderate to severe ulcerative colitis
  • Moderate to severe Crohn’s disease
  • Used when response to TNF-α inhibitors or conventional therapy is inadequate

Adverse Effects

  • Nasopharyngitis
  • Headache
  • Arthralgia
  • Nausea
  • Infusion reactions
  • Rare risk of progressive multifocal leukoencephalopathy (PML)

Comparative Analysis

DrugTargetSelectivityRisk of PML
Vedolizumabα4β7 integrinGut-specificLow (theoretical)
Natalizumabα4 and α4β7 integrinsSystemicHigh
InfliximabTNF-αSystemicModerate

MCQs

  1. Vedolizumab selectively binds to which integrin?
    a) α4β1 b) α4β7 c) αvβ3 d) β2
    Answer: b) α4β7
  2. The primary site of action of vedolizumab is:
    a) Liver b) CNS c) Gut d) Skin
    Answer: c) Gut
  3. Vedolizumab prevents the interaction between α4β7 integrin and:
    a) VCAM-1 b) ICAM-1 c) MAdCAM-1 d) PECAM-1
    Answer: c) MAdCAM-1
  4. One advantage of vedolizumab over natalizumab is:
    a) Oral bioavailability b) CNS penetration c) Lower risk of PML d) Faster onset
    Answer: c) Lower risk of PML
  5. Half-life of vedolizumab is approximately:
    a) 7 days b) 12 days c) 25.5 days d) 40 days
    Answer: c) 25.5 days
  6. Route of administration for vedolizumab is:
    a) Oral b) Subcutaneous c) Intravenous d) Intramuscular
    Answer: c) Intravenous
  7. Which of the following is a common side effect?
    a) Nephrotoxicity b) Nausea c) Anemia d) Bradycardia
    Answer: b) Nausea
  8. Vedolizumab is mainly used in:
    a) Asthma b) Ulcerative colitis and Crohn’s disease c) Rheumatoid arthritis d) Multiple sclerosis
    Answer: b) Ulcerative colitis and Crohn’s disease
  9. How does vedolizumab maintain systemic immunity?
    a) Non-specific inhibition b) Local action in CNS c) Gut-selective targeting d) Hepatic metabolism
    Answer: c) Gut-selective targeting
  10. The interaction between α4β7 and MAdCAM-1 occurs in the:
    a) Brain b) Gut c) Kidney d) Lung
    Answer: b) Gut

FAQs

1. How is vedolizumab administered?
Intravenously at weeks 0, 2, and 6 for induction, followed by every 8 weeks for maintenance.

2. Can vedolizumab be used in both UC and Crohn’s disease?
Yes, it is approved for both moderate to severe ulcerative colitis and Crohn’s disease.

3. Does it suppress the entire immune system?
No, it selectively modulates immune response in the gut, minimizing systemic immunosuppression.

4. What is the onset of action?
Clinical improvement is usually observed within 6 to 14 weeks.

5. Is JC virus testing required before use?
Not mandatory, as the risk of PML is theoretical and extremely low with gut-specific action.

References

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