Etanercept

Etanercept is a recombinant fusion protein of the human p75 TNF receptor and the Fc portion of human IgG1, given subcutaneously. It is used in rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis and plaque psoriasis. It is not effective in inflammatory bowel disease, uveitis or granulomatous disease, and carries a lower tuberculosis reactivation risk than the monoclonal anti-TNF antibodies.

Class. Soluble TNF receptor fusion protein, biological disease-modifying drug.

Mechanism. It binds soluble TNF alpha and lymphotoxin alpha, acting as a decoy receptor, with little binding to transmembrane TNF.

Pharmacokinetics. Subcutaneous bioavailability about 76 percent, half-life about 70 hours, steady state about 2 to 3 weeks. It has minimal placental transfer in comparison with full-length antibodies.

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. 50 mg subcutaneously once weekly, or 25 mg twice weekly (72 to 96 hours apart). Loading dose: none. Maximum dose: 50 mg weekly.

Plaque psoriasis. 50 mg twice weekly for 3 months, then 50 mg once weekly; or 25 mg twice weekly throughout. Maximum dose: 100 mg weekly for the first 3 months.

Polyarticular juvenile idiopathic arthritis (2 years and over). 0.8 mg/kg once weekly (maximum 50 mg) or 0.4 mg/kg twice weekly (maximum 25 mg each dose).

Paediatric plaque psoriasis (6 years and over). 0.8 mg/kg once weekly, maximum 50 mg, for up to 24 weeks.

Concomitant therapy. Methotrexate may be continued in rheumatoid arthritis for additive effect and to reduce antibody formation.

Contraindications. Sepsis or active serious infection, and hypersensitivity. Avoid in moderate to severe heart failure.

Boxed-warning-level risks. Serious infections (tuberculosis, invasive fungal, bacterial), malignancy including lymphoma in children and adolescents.

Adverse effects. Common: injection site reactions, upper respiratory infection, headache. Serious: serious infection, hepatitis B reactivation, demyelinating disease, cytopenias including aplastic anaemia, lupus-like syndrome, worsening heart failure, new or worsening psoriasis, and autoimmune hepatitis.

Major interactions. Anakinra and abatacept (avoid), cyclophosphamide (malignancy), sulfasalazine (neutropenia), live vaccines (avoid).

Common prescribing errors. Using in Crohn disease or uveitis expecting benefit; skipping infection screening; confusing weekly and twice weekly dosing.

Special groups.

• Pregnancy: lowest placental transfer among the anti-TNF antibodies and receptor constructs; can be continued through pregnancy where needed.

• Breastfeeding: compatible.

• Children: 0.8 mg/kg once weekly, maximum 50 mg (2 years and over).

• Older adults: higher infection risk.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment; caution in alcoholic hepatitis.

• Region: tuberculosis and hepatitis B screening before starting remains necessary.

Formulations. 25 mg and 50 mg prefilled syringes and pens. Store at 2 to 8 degrees Celsius; may be kept at room temperature for up to 4 weeks.

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

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

Stop or hold thresholds. Serious infection, new demyelination, unexplained cytopenia, lupus-like syndrome, or heart failure.

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