Last updated: October 17, 2014
Trade Names: Enbrel
Drug Class: Biologic DMARD, TNF antagonist
Preparations: 25-mg and 50-mg injection
Dose: for RA, ankylosing spondylitis and psoriatic arthritis 50 mg by subcutaneous injection once a week or 25 mg twice weekly
Mechanism of Action: Etanercept is a dimer of p75 TNF receptors fused to the Fc portion of IgG1. The addition of IgG1 increases the half-life. Etanercept binds to TNF and blocks its ability to bind with its receptor on the cell.
Contraindications: Hypersensitivity, untreated tuberculosis or other opportunistic infections, sepsis, active infections, chronic localized or recurrent infections, demyelinating disease, optic neuritis or heart failure
Precautions: Increased risk of serious infections including TB and fungal. Exclude latent or active TB with a skin test or TB blood test (interferon-gamma release assays or IGRA). Caution in debilitated or high risk of infection. Exclude active hepatitis B infection or carriage. Avoid live virus vaccines and BCG. Do not use with other biologics. May exacerbate pre-exisiting demyelinating disease and heart failure.
Monitoring: Monitor clinically for infection and periodic CBC. After therapy started, additional TB testing may be indicated for individuals likely to have exposure to TB.
Pregnancy Risk: B
Common: Injection site reactions, positive antinuclear and double stranded DNA antibody
Less common: Allergy, infection (bacterial, but particularly opportunistic infections such as tuberculosis, listeriosis, and histoplasmosis).
Rare: Lymphoma (including fatal hepatosplenic T-cell lymphoma), hepatitis, demyelinating CNS disorders, optic neuritis, seizures, pancytopenia, drug-induced lupus, reactivation of hepatitis B, new onset psoriasis.
Drug Interactions: Concurrent use of other immunosuppressants may increase risk of infection.
Patient Instructions: Avoid live virus vaccines. Avoid pregnancy. Stop injections if an infection develops that requires antibiotics or a fever develops that lasts more than a few days.
Comments: TNF antagonists are among the most effective treatments for RA. Patients start to respond quickly, usually within 4–6 weeks but maximum response may take 4-6 months. In RA, combined therapy with an anti-TNF drug and MTX is more effective than either drug alone. TNF antagonists are being explored in a range of diseases such as sarcoidosis and inflammatory eye disease. Risk of tuberculosis may be lower with etanercept than other TNF antagonists; comparative risk of adverse effects among individual TNF antagonists is not clear and side effects likely a class effect. Patients may form antibodies to anti-TNF drugs that decrease their effect. Concurrent treatment with MTX may reduce the frequency of this.
Clinical Pharmacology: Half-life is 4–5 days. Biologic agents are not metabolized and thus have few drug interactions.
Bombardier C, Hazlewood GS, Akhavan P, et al. Canadian Rheumatology Association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: part II safety. J Rheumatol 2012;39:1583-602. PMID: 22707613.
Singh JA, Furst DE, Bharat A. et al.2012 Update of the 2008 American College of Rheumatology recommendations for the use ofdisease-modifyingantirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis.Arthritis Care Res 2012;64(5):625-39.PMID:22473917