Adalimumab for Inflammatory Bowel Disease

Adalimumab is a fully human monoclonal antibody against tumour necrosis factor alpha, given by subcutaneous injection. It is used for moderate to severe Crohn disease and ulcerative colitis when conventional treatment has failed or is not tolerated. It is less immunogenic than infliximab but is not suited to acute severe colitis.

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

Mechanism. Binds soluble and membrane-bound tumour necrosis factor alpha, blocking its interaction with p55 and p75 receptors and neutralising inflammation.

Pharmacodynamics. Response at 2 to 4 weeks; maximum effect at 12 weeks or later.

Pharmacokinetics. Subcutaneous bioavailability about 64%. Peak at about 5 days. Half-life about 2 weeks. Clearance is increased by anti-drug antibodies, high body weight and low albumin.

Metabolism. Proteolytic catabolism.

Adult subcutaneous doses.

Crohn disease, moderate to severe.

• Induction: 160 mg at week 0, then 80 mg at week 2.

• Maintenance: 40 mg every 2 weeks, starting at week 4.

• If response is lost, increase to 40 mg weekly or 80 mg every 2 weeks.

Ulcerative colitis, moderate to severe.

• Induction: 160 mg at week 0, then 80 mg at week 2.

• Maintenance: 40 mg every 2 weeks, or 80 mg every 2 weeks if needed.

• Stop if there is no evidence of response by week 8.

Children with Crohn disease (age 6 to 17 years).

• Under 40 kg: 80 mg at week 0, 40 mg at week 2, then 20 mg every 2 weeks.

• 40 kg and over: 160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks.

Combination therapy. With azathioprine or methotrexate to reduce antibody formation.

Kidney and liver adjustment. None.

Contraindications. Active tuberculosis or other severe infection; moderate to severe heart failure; hypersensitivity.

Common adverse effects. Injection site reactions, upper respiratory infection, headache, rash and raised liver enzymes.

Serious adverse effects.

• Serious infections including tuberculosis, invasive fungal infections, hepatitis B reactivation, and opportunistic infection.

• Lymphoma and other malignancy; hepatosplenic T-cell lymphoma with thiopurine combination in young males.

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

• Hypersensitivity and anaphylaxis (rare).

• Paradoxical psoriasis.

Major interactions.

• Other biologics (anakinra, abatacept): increased infection risk; avoid.

• Live vaccines: contraindicated during treatment.

• Azathioprine and mercaptopurine: additive myelosuppression and infection risk.

• Methotrexate: lowers adalimumab clearance, reducing antibodies.

Special groups.

• Pregnancy: placental transfer in late pregnancy; continue if needed to control disease; avoid live vaccines in the infant for 6 to 12 months.

• Breastfeeding: negligible transfer; compatible.

• Children: approved from 6 years in Crohn disease.

• Older adults: higher infection risk.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment.

• Regional: tuberculosis and hepatitis B are common in East Africa, and cost limits access; biosimilars can lower cost.

Formulations. Prefilled pens and syringes 20 mg, 40 mg and 80 mg; biosimilars.

Administration.

• Inject into the thigh or abdomen; rotate sites. Do not inject into tender, bruised or red skin.

• Remove from the refrigerator 15 to 30 minutes before injecting; store at 2 to 8 degrees Celsius and do not freeze.

• Patients can self-inject after training.

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

Monitoring.

• Infection signs, injection site reactions and neurological symptoms.

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

• Trough level and antibodies when response is lost.

• Faecal calprotectin and endoscopy to confirm response.

• Skin examination yearly.

Therapeutic drug monitoring. Target trough about 5 to 12 micrograms/mL for luminal disease.

Stopping. Stop for serious infection, severe hypersensitivity, malignancy, demyelination or heart failure.

Referral and escalation. Specialist gastroenterology care throughout. Switch within class or class to another mechanism if there is primary non-response or loss of response with antibodies.