Infliximab

Infliximab is a chimeric monoclonal IgG1 antibody to tumour necrosis factor alpha, given by intravenous infusion, with a long record in rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, psoriasis, Crohn disease, ulcerative colitis and several off label inflammatory conditions. It is the anti-TNF of choice for acute severe ulcerative colitis, uveitis, sarcoidosis and Behcet disease with visceral involvement. Biosimilar versions are used and are not distinguished here.

Class. Anti-tumour necrosis factor monoclonal antibody, biological disease-modifying drug.

Mechanism. It binds soluble and transmembrane TNF alpha, neutralising signalling, causing apoptosis of TNF-expressing cells and reducing inflammatory cytokines and cell recruitment.

Pharmacokinetics. Intravenous only, with a half-life of 8 to 10 days, dose-proportional levels, clearance raised by anti-drug antibodies, low albumin, high body weight and severe inflammation. It crosses the placenta mainly in the third trimester.

All regimens use 0, 2 and 6 week induction infusions then maintenance, given over at least 2 hours.

Rheumatoid arthritis (with methotrexate). 3 mg/kg at weeks 0, 2 and 6, then every 8 weeks. Titrate to a maximum of 10 mg/kg or shorten the interval to every 4 weeks if response is inadequate.

Ankylosing spondylitis and axial spondyloarthritis. 5 mg/kg at weeks 0, 2 and 6, then every 6 to 8 weeks.

Psoriatic arthritis and plaque psoriasis. 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks.

Crohn disease and ulcerative colitis. 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks; dose intensification to 10 mg/kg or every 4 to 6 weeks for loss of response. Fistulising Crohn disease uses the same induction.

Acute severe ulcerative colitis (steroid refractory, specialist). 5 mg/kg, repeated at weeks 2 and 6 in responders; some centres use 10 mg/kg in high-risk disease.

Paediatric Crohn disease and ulcerative colitis (6 years and over). 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks.

Loading dose. The three induction infusions serve as the loading regimen. Maximum dose: 10 mg/kg for each infusion in approved indications.

Concomitant immunomodulator. Methotrexate in rheumatoid arthritis (7.5 to 25 mg weekly) or azathioprine in inflammatory bowel disease reduces anti-drug antibodies and infusion reactions.

Contraindications. Active tuberculosis or other serious infection including sepsis, moderate to severe heart failure (NYHA class III or IV), and hypersensitivity to murine proteins.

Boxed-warning-level risks. Serious infections (tuberculosis, invasive fungal infection, bacterial and opportunistic infection) and malignancy, including hepatosplenic T cell lymphoma mainly in adolescent and young adult males with inflammatory bowel disease taking thiopurines.

Adverse effects. Common: infusion reactions, headache, infections of the upper respiratory tract, nausea, raised liver enzymes. Serious: tuberculosis reactivation, hepatitis B reactivation, demyelination, drug-induced lupus, worsening heart failure, delayed serum sickness (days 3 to 12), cytopenias, anaphylaxis, hepatotoxicity, psoriasiform skin lesions.

Major interactions. Anakinra and abatacept (avoid; serious infection), other biologics, live vaccines (avoid), and thiopurines (lymphoma risk).

Common prescribing errors. Starting without tuberculosis and hepatitis B screening; omitting immunomodulator cover; stopping and restarting after a gap without a desensitisation or switch plan; continuing in heart failure.

Special groups.

• Pregnancy: can be continued where needed to control disease, but stop at about 24 to 30 weeks in patients in remission to limit placental transfer. If used late in pregnancy, avoid live vaccines (BCG, rotavirus) in the infant for 12 months.

• Breastfeeding: compatible.

• Children: 5 mg/kg at weeks 0, 2 and 6 then every 8 weeks (6 years and over); specialist only.

• Older adults: higher infection risk; check cardiac status.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment; monitor enzymes.

• Region: tuberculosis, hepatitis B, histoplasmosis and other endemic fungal infection risk is high in East Africa; screen with interferon gamma release assay or tuberculin test and chest radiograph, and consider chemoprophylaxis for latent infection before the first dose.

Formulations. 100 mg lyophilised vials. Reconstitute with 10 mL sterile water, dilute to 250 mL in 0.9 percent sodium chloride and infuse over 2 hours through a low protein binding 1.2 micrometre filter. Subsequent infusions in stable patients may be shortened to 1 hour in selected centres.

Baseline. Tuberculosis screen, hepatitis B surface antigen and core antibody, hepatitis C and HIV serology, full blood count, liver enzymes, chest radiograph, cardiac status, vaccination update (no live vaccines), and pregnancy test.

Monitoring. Observe during and for 1 hour after the first infusions. Full blood count, liver enzymes and disease activity at each infusion. In inflammatory bowel disease, trough levels about 5 to 10 micrograms/mL and anti-drug antibodies when response falls.

Stop or hold thresholds. Serious infection, new demyelinating symptoms, lupus-like syndrome, severe infusion reaction, heart failure, or malignancy.

Infusion reaction management. Slow or stop the infusion; give antihistamine, hydrocortisone and paracetamol for mild reactions; for anaphylaxis give intramuscular adrenaline 0.5 mg (adult) and do not rechallenge.

Referral and escalation. Specialist initiated. Refer for secondary loss of response, anti-drug antibodies, or serious infection.