Vedolizumab

Vedolizumab is a gut-selective humanised monoclonal antibody against alpha-4 beta-7 integrin. It blocks lymphocyte trafficking into the gut, with little systemic immunosuppression. It is used for moderate to severe ulcerative colitis and Crohn disease after failure of conventional therapy or anti-TNF agents, and is often chosen where infection or malignancy risk is a concern.

Classification. Biologic; integrin receptor antagonist (gut-selective).

Mechanism. Binds alpha-4 beta-7 integrin on a subset of memory T cells and blocks its interaction with mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on gut endothelium, preventing T cell entry into inflamed gut tissue.

Pharmacodynamics. Slow onset; response may take 10 to 14 weeks.

Pharmacokinetics. Half-life about 25 days. Clearance is higher with low albumin, high weight and anti-drug antibodies (rare).

Metabolism. Proteolytic catabolism.

Adult doses.

Ulcerative colitis and Crohn disease, moderate to severe (intravenous).

• 300 mg infusion at weeks 0, 2 and 6, then 300 mg every 8 weeks.

• Stop if there is no benefit by week 14.

• Interval can be shortened to every 4 weeks if response is lost.

Subcutaneous maintenance (after at least 2 intravenous doses). 108 mg every 2 weeks.

Children. Not established in most labels.

Kidney and liver adjustment. None.

Contraindications. Active severe infection (tuberculosis, sepsis, cytomegalovirus, listeriosis, progressive multifocal leukoencephalopathy); hypersensitivity.

Common adverse effects. Nasopharyngitis, headache, arthralgia, nausea, fatigue and cough.

Serious adverse effects.

• Infusion-related reactions and anaphylaxis (rare).

• Serious infections, including gastrointestinal infection, though systemic infections are less common than with anti-TNF drugs.

• Liver injury (rare).

• Progressive multifocal leukoencephalopathy has not been confirmed, but neurological changes need urgent evaluation.

Major interactions.

• Other biologics, particularly natalizumab: avoid.

• Live vaccines: avoid during treatment.

• Anti-TNF drugs: avoid combination.

• Immunomodulators: not required routinely.

Special groups.

• Pregnancy: limited data; placental transfer is expected late in pregnancy; continue if needed to control disease.

• Breastfeeding: low transfer; probably compatible.

• Children: not established.

• Older adults: favoured because of lower systemic risk.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment; monitor liver tests.

• Regional: limited availability and high cost in East Africa; tuberculosis and hepatitis B screening are still needed.

Formulations. Powder for infusion 300 mg vial; subcutaneous prefilled pen or syringe 108 mg.

Preparation and infusion.

• Reconstitute with 4.8 mL of sterile water for injection and swirl gently for 15 seconds; do not shake.

• Dilute to a total of 250 mL in 0.9% sodium chloride.

• Infuse over 30 minutes; flush after the infusion.

• Observe for infusion reactions during and for 1 hour after the first two infusions.

Baseline. Tuberculosis screening, hepatitis B, hepatitis C and HIV, full blood count, liver tests, pregnancy test and vaccination review.

Monitoring.

• Infusion reactions and infection signs.

• Liver tests every 3 to 6 months.

• Response at weeks 10 to 14 by symptoms, faecal calprotectin and endoscopy.

• Neurological symptoms such as weakness, visual change or confusion.

Therapeutic drug monitoring. Trough levels may guide dosing (target about 20 micrograms/mL or higher); availability is limited.

Stopping. Stop for serious infection, anaphylaxis, suspected progressive multifocal leukoencephalopathy, liver injury or no benefit at week 14.

Referral and escalation. Specialist gastroenterology care throughout. Not suited to acute severe colitis because of the slow onset.