An overview of etanercept (Enbrel): how it works and adverse events

This article reviews how etanercept (Enbrel) works and what adverse events it may cause in patients with rheumatic diseases.

Patients with rheumatic diseases (such as rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis and juvenile idiopathic arthritis) have increased local or general inflammation. Etanercept was approved for treating these diseases over a decade ago. It works by blocking TNFalpha, a protein normally produced by the immune system during inflammation. As patients with rheumatic diseases have increased inflammation they have more TNFalpha. By blocking TNFalpha, etanercept can relieve patients’ symptoms and prevent further joint damage. As a result of these improvements patients can also benefit from improved quality of life and reduced disability.

How is it taken?

Etanercept is injected under the skin. For adults with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis the injection is normally done once per week and contains 50 mg/ml of etanercept. However, 25 mg/ml injections given over two injections may be preferred and is as effective. In adult patients with plaque psoriasis the recommended starting dose is 50 mg/ml twice weekly for 3 months. After 3 months the dose is lowered to 50 mg/ml once per week. (All doses and recomendations are those of the United States; those of the European Union differ slightly).

Children with juvenile idiopathic arthritis can be prescribed etanercept from the age of 2 (Europe and America), but it is not recommended until age 6 for children with plaque psoriasis (Europe only, not yet approved for children in the US). For children the doctor will prescribe a dose based on the child’s weight. This lower dose is given as an injection under the skin once or twice per week. It is recommended that etanercept is stopped if children’s symptoms do not improve within 12 (plaque psoriasis) to 16 weeks (juvenile idiopathic arthritis) of starting treatment.

Adverse events:

For adults and children taking etanercept most adverse events are of mild or moderate intensity. The most common problems include reactions at the injection site and infections (such as mild to moderate lung infections, bladder infections and skin infections). In clinical trials roughly 37% of patients developed reactions at the site of the injection (pain, swelling, itching, redness or bleeding). These were mild to moderate reactions and generally did not lead to patients stopping treatment. On average the reaction only lasted 3 to 5 days and generally occurred in the first month of treatment.

Treatment with etanercept may increase patients’ risk of developing cancer or serious infections. Etanercept comes with a warning regarding these risks. It is recommended that children be up-to-date with their vaccinations prior to the start of etanercept treatment. There have also been some rare cases of other adverse events (less than 0.1% of patients) including worsening or onset of heart failure or disorders of the nervous system. 

The author concluded that etanercept has revolutionized the management of rheumatic diseases and that it continues to have a central role in treating patients.

The author discussed both European and American guidelines. The dosage information may vary depending on where a patient is living.