Infliximab for Inflammatory Bowel Disease

Infliximab is a chimeric monoclonal antibody against tumour necrosis factor alpha. It is used for moderate to severe Crohn disease, fistulising Crohn disease and moderate to severe ulcerative colitis, including acute severe colitis not responding to intravenous steroids. Biosimilars are available and cheaper.

Classification. Biologic; anti-TNF monoclonal antibody (chimeric IgG1).

Mechanism. Binds soluble and membrane-bound tumour necrosis factor alpha, neutralising its activity and inducing apoptosis of activated inflammatory cells. This reduces mucosal inflammation and promotes mucosal healing.

Pharmacodynamics. Response starts within 2 weeks; maximum effect at 6 to 14 weeks. Antibodies to infliximab and low trough levels reduce response over time.

Pharmacokinetics. Intravenous infusion. Half-life 7.7 to 9.5 days. Clearance is higher with low albumin, high weight, severe colitis, anti-drug antibodies and high TNF burden, so acute severe colitis often needs higher or accelerated dosing.

Metabolism. Cleared by proteolytic catabolism; no cytochrome P450 involvement.

Adult intravenous doses. Infuse over at least 2 hours.

Crohn disease, moderate to severe, and ulcerative colitis.

• Induction: 5 mg/kg at weeks 0, 2 and 6.

• Maintenance: 5 mg/kg every 8 weeks.

• If response is lost, increase to 10 mg/kg every 8 weeks or shorten the interval to every 4 to 6 weeks, using trough levels.

Fistulising Crohn disease. 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks; combine with antibiotics and seton drainage for perianal abscess.

Acute severe ulcerative colitis (steroid-refractory).

• 5 mg/kg as a single dose, or 10 mg/kg if high risk (low albumin, high inflammation, high weight).

• Accelerated dosing: second dose within 1 to 3 weeks, specialist directed.

Subcutaneous maintenance (specialist). 120 mg every 2 weeks after at least two intravenous induction doses in some markets.

Children (age 6 to 17 years). 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks.

Combination therapy. Use with azathioprine 2 to 2.5 mg/kg daily or methotrexate 25 mg weekly to reduce antibody formation and improve response. Alternatively use low-dose azathioprine with therapeutic drug monitoring.

Kidney and liver adjustment. None.

Contraindications.

• Active tuberculosis or other severe infection (sepsis, abscess, opportunistic infection).

• Moderate to severe heart failure (NYHA class III or IV).

• Hypersensitivity to infliximab, murine proteins or excipients.

Common adverse effects. Infusion reactions (fever, chills, flushing, rash), headache, upper respiratory infection, nausea, abdominal pain and raised liver enzymes.

Serious adverse effects.

• Serious infections: tuberculosis (often extrapulmonary and disseminated), invasive fungal infection, bacterial sepsis, hepatitis B reactivation and opportunistic infection.

• Delayed hypersensitivity (serum sickness-like illness) 3 to 12 days after infusion.

• Infusion reactions, including anaphylaxis, which are more likely with antibodies.

• Lymphoma, including hepatosplenic T-cell lymphoma in young men on thiopurine combination; skin cancer.

• Demyelinating disease, drug-induced lupus, heart failure, liver injury, cytopenias.

• Paradoxical psoriasis.

Major interactions.

• Other biologic immunosuppressants (anakinra, abatacept, tocilizumab): increased infection risk; avoid.

• Live vaccines: contraindicated during treatment; infants exposed in utero should not receive live vaccines for 12 months.

• Azathioprine and mercaptopurine: lower antibody rate but higher lymphoma and infection risk.

• Warfarin and ciclosporin: monitor levels when disease activity changes.

Special groups.

• Pregnancy: placental transfer is greatest in the third trimester. Continue to control disease; consider stopping at about week 24 to 30 if disease is quiet, or time the dose to reduce transfer.

• Breastfeeding: negligible transfer; compatible.

• Children: approved from 6 years in Crohn disease and ulcerative colitis.

• Older adults: higher infection risk.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment; monitor liver tests.

• Tuberculosis and hepatitis B screening are essential.

• Regional: tuberculosis and hepatitis B are common in East Africa; strict screening and treatment of latent tuberculosis are required, and access and cost limit use.

Formulations. Powder for infusion 100 mg vial; subcutaneous prefilled pen 120 mg in some markets; biosimilars.

Preparation and infusion.

• Reconstitute each 100 mg vial with 10 mL of sterile water for injection; swirl gently, do not shake.

• Dilute the required dose in 250 mL of 0.9% sodium chloride.

• Infuse through a 1.2 micron low protein-binding filter over at least 2 hours, with the first dose slow.

• Complete infusion within 3 hours of reconstitution.

• Keep a resuscitation kit available and observe for at least 1 hour after the infusion.

Baseline.

• Tuberculosis screening (chest imaging and interferon gamma release assay or tuberculin test); hepatitis B surface antigen and core antibody; hepatitis C and HIV.

• Full blood count, liver tests and pregnancy test.

• Vaccination review before starting (live vaccines first, at least 4 weeks before).

Monitoring.

• Infusion reactions, infection signs and symptoms of lupus or demyelination.

• Full blood count and liver tests every 3 to 6 months.

• Trough infliximab level and anti-drug antibodies at induction end and when response is lost.

• Faecal calprotectin and endoscopy for mucosal healing.

• Skin examination yearly.

Therapeutic drug monitoring. Target trough 5 to 10 micrograms/mL in luminal disease and higher in fistulising disease (above 10 micrograms/mL).

Stopping. Stop for serious infection, severe infusion reaction, heart failure, malignancy or demyelination. Relapse risk rises after stopping; antibodies make restarting riskier.

Referral and escalation. Specialist gastroenterology care throughout. Urgent admission for acute severe colitis.