Certolizumab Pegol

Certolizumab pegol is a PEGylated Fab fragment of a humanised anti-TNF antibody, with no Fc region. The absence of Fc greatly reduces active placental transfer and breast milk transfer, making it the usual anti-TNF choice in pregnancy. It is used in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, plaque psoriasis and Crohn disease.

Class. Anti-tumour necrosis factor Fab fragment, PEGylated.

Mechanism. Binds soluble and transmembrane TNF alpha and neutralises it, without complement activation or antibody-dependent cytotoxicity because it lacks Fc.

Pharmacokinetics. Subcutaneous bioavailability about 80 percent, half-life about 14 days, slow clearance, minimal to undetectable placental transfer and milk transfer.

Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis.

• Loading dose: 400 mg subcutaneously (two 200 mg injections) at weeks 0, 2 and 4.

• Maintenance dose: 200 mg every other week, or 400 mg every 4 weeks.

• Maximum dose: 400 mg for each dose.

Plaque psoriasis. 400 mg every other week; 200 mg every other week may be enough for patients of 90 kg or less after week 16.

Crohn disease. 400 mg at weeks 0, 2 and 4, then 400 mg every 4 weeks.

Methotrexate co-therapy. Reduces antibody formation in rheumatoid arthritis.

Contraindications. Active tuberculosis or serious infection, moderate to severe heart failure, and hypersensitivity (including to polyethylene glycol).

Boxed-warning-level risks. Serious infections and malignancy, including lymphoma in children and adolescents on TNF blockers.

Adverse effects. Common: upper respiratory infection, rash, injection site reactions, headache. Serious: tuberculosis and hepatitis B reactivation, demyelination, lupus-like syndrome, cytopenias, heart failure, hypersensitivity, new or worsening psoriasis.

Major interactions. Anakinra and abatacept (avoid), other biologics, live vaccines (avoid). Certolizumab pegol falsely prolongs the activated partial thromboplastin time with some assays.

Common prescribing errors. Interpreting a prolonged activated partial thromboplastin time as a clotting disorder; skipping loading doses; missing polyethylene glycol allergy.

Special groups.

• Pregnancy: acceptable throughout pregnancy where needed; negligible placental transfer.

• Breastfeeding: compatible.

• Children: not established for routine rheumatological use in many regions.

• Older adults: higher infection risk.

• Kidney impairment: no data for a dose adjustment; use with caution.

• Liver impairment: no data; use with caution.

• Region: screen for tuberculosis and hepatitis B; refrigerated storage needed.

Formulations. 200 mg prefilled syringes or pens. Store at 2 to 8 degrees Celsius; may be kept at room temperature for up to 10 days.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, full blood count, liver enzymes, chest radiograph, vaccination update.

Monitoring. Disease activity and infection symptoms at each visit; blood count periodically.

Stop or hold thresholds. Serious infection, demyelination, lupus-like syndrome, severe hypersensitivity, or malignancy.

Referral and escalation. Specialist initiated. Refer for inadequate response at 12 weeks.