EtanerceptRx

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

Indications: RA, psoriatic arthritis, psoriasis, ankylosing spondylitis, polyarticular juvenile idiopathic arthritis

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

Adverse Effects
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.

Cost: $$$$$

BIBLIOGRAPHY

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