Makindo Medical Notes

💡 Vedolizumab (Entyvio®) is a gut-selective monoclonal antibody that blocks lymphocyte trafficking to the intestinal mucosa. It is a biologic therapy for moderate to severe Ulcerative Colitis and Crohn’s Disease refractory to conventional or anti-TNF therapy.

🧠 About

• Humanised monoclonal antibody (IgG1 subclass).
• Cost: NHS list price ≈ £2050 per 300 mg vial (excluding administration costs).
• Licensed in the UK for Ulcerative colitis (UC) and Crohn’s disease (CD) under NICE guidance TA342 and TA352.
• Assessment for continuation is advised at least every 12 months to ensure ongoing response.

⚙️ Mechanism of Action

• Binds specifically to the α4β7 integrin on gut-homing T-helper lymphocytes.
• This prevents adhesion to Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) on the gut endothelium.
• Result: Selective inhibition of lymphocyte migration into gut tissue → reduced inflammation in intestinal mucosa.
• Unlike natalizumab, it does not affect α4β1 integrin → minimal CNS penetration → much lower risk of PML (progressive multifocal leukoencephalopathy).

🎯 Indications

• Ulcerative colitis (UC): Moderate-to-severe active disease unresponsive or intolerant to corticosteroids, immunomodulators (azathioprine, 6-MP), or anti-TNF agents.
• Crohn’s disease (CD): Moderate-to-severe disease unresponsive to conventional therapy.
• May be used as a steroid-sparing maintenance therapy.

💉 Dose and Administration

• Induction phase: 300 mg IV infusion at weeks 0, 2, and 6.
• Maintenance: 300 mg IV every 8 weeks thereafter.
• Patients not showing benefit by week 14 should discontinue therapy.
• Infusion is given over 30 minutes; observe for hypersensitivity or infusion-related reactions during and post-infusion.

⚠️ Cautions

• Screen for tuberculosis, hepatitis B, and active infection before starting treatment.
• Delay initiation in presence of severe or systemic infection.
• Monitor for opportunistic infections during treatment.
• Do not combine with other biologics targeting the immune system (e.g., anti-TNF, natalizumab).

🚫 Contraindications

• Known hypersensitivity to vedolizumab or excipients.
• Severe active infections (e.g., sepsis, TB, abscess).
• History of PML (progressive multifocal leukoencephalopathy).

💊 Adverse Effects

• Very common: Nasopharyngitis, headache, arthralgia.
• Common: Fatigue, nausea, abdominal pain, rash, pruritus.
• Occasional: Infusion-related reactions (fever, urticaria, rigors), raised transaminases.
• Rare: Hypersensitivity or anaphylaxis.
• Infection risk is lower than with anti-TNF drugs due to gut-selective action.

🧩 Monitoring and Review

• Baseline: FBC, LFT, CRP, ESR, hepatitis B/C and HIV screening, TB screening (IGRA).
• Assess symptom improvement, CRP, and stool calprotectin at 14 weeks.
• Reassess every 6–12 months for efficacy and need for continued biologic therapy.
• Vaccinate for influenza and pneumococcus before initiation if possible (avoid live vaccines during therapy).

💷 Cost and NICE Appraisal

• NICE TA342 (UC) and TA352 (Crohn’s) recommend vedolizumab for patients in whom:
  • Conventional therapy or TNF-α inhibitors have failed or are not tolerated.
  • It is provided at the manufacturer’s agreed confidential discount price to the NHS.

🧠 Teaching Notes

• Vedolizumab represents a new class: gut-selective anti-integrin therapy.
• Compared to infliximab or adalimumab, it has slower onset but excellent safety profile for long-term use.
• Good for older adults or patients with infection risk where anti-TNF is unsuitable.
• Loss of response may occur — dose interval can be shortened to every 4 weeks.

📚 References

• BNF: Vedolizumab
• NICE TA342 (2015): Vedolizumab for treating moderate to severe ulcerative colitis.
• NICE TA352 (2015): Vedolizumab for treating moderate to severe Crohn’s disease.
• Feagan BG et al. NEJM 2013;369:699–710. “Vedolizumab as induction and maintenance therapy for UC.”