Etanercept (brand name Enbrel®) belongs to the class of biological response modifiers called tumour necrosis factor (TNF) blockers. TNF is a cytokine – a messenger chemical.
Etanercept is approved for the treatment of psoriatic arthritis and psoriasis in adults and children from 4 years of age. Other indications include treatment of rheumatoid arthritis, ankylosing spondylitis and polyarticular-course juvenile rheumatoid arthritis. Clinical trials have shown that it is well tolerated and significantly improves psoriatic target lesions.
In New Zealand, in November 2010, PHARMAC approved funding for severe treatment-resistant psoriasis on Special Authority application.
How does etanercept work?
Etanercept is genetically engineered from human protein. It works by directly binding to TNF molecules in the blood and diseased tissue. Etanercept-bound TNF cannot bind to or activate TNF receptors. TNF is involved in normal inflammatory and immune processes, and is there are high levels in skin affected by psoriasis.
How effective is etanercept in psoriasis?
Randomised, double-blind, placebo-controlled studies of etanercept in moderate-to-severe chronic plaque psoriasis showed that it significantly decreased disease activity (PASI score) with a favourable safety profile.
The PRESTA trial of bi-weekly dosing for 12 weeks then 50mg once weekly reported that 70% of patients with moderate-to-severe chronic plaque psoriasis and psoriatic arthritis on etanercept achieved PASI 75 by week 24. It was also effective for psoriatic arthritis, with 77% achieving psoriatic arthritis response criteria. The similar PRISTINE trial reported 78% achieved PASI 75 by week 24, with the use of unrestricted additional topical medications after week 12.
How is etanercept given?
Etanercept is given by subcutaneous injection. The usual dose for psoriasis is 50 mg twice weekly for the first twelve weeks, then once weekly. After initial counselling and training by a health professional on how to prepare and inject the drug, patients can usually self-administer at home using a pre-filled syringe or autoinjector. Injections are usually into the thigh, abdomen or upper arm. A different site should be used at each injection to reduce soreness and prevent the skin from becoming tender, red, bruised or hard.
Etanercept can be give alone or if necessary, in combination with topical treatments, methotrexate, and/or phototherapy.
In children, the dose is 0.8 mg/kg up to a maximum dose of 50mg once weekly.
Etanercept injections needs to be kept cold, including when travelling. See travel letter below, which explains the need to carry the medication as hand luggage.
Precautions necessary for patients on etanercept
Regular follow-up visits to the doctor are necessary whilst on etanercept.
Because etanercept works by selectively targeting a cytokine involved in psoriatic arthritis and/or psoriasis, theoretically it should have little effect on the rest of the body's immune system. Even so caution must be taken when considering its use in patients prone to infections or in those with chronic or recurrent infections. It should not be used in patients with sepsis or active infections in case it makes these worse.
The incidence of etanercept-associated cases of tuberculosis (TB) is lower than that seen with infliximab, hence TB screening before starting etanercept is not required by the FDA. However, current practice is to perform tuberculin skin testing for all biological medicines before commencing treatment.
There is concern that etanercept may reactivate viral hepatitis in chronic carriers of hepatitis B and C, so symptoms, liver function and viral load should be monitored on treatment.
Uncommon infections with organisms such as listeria and legionella may be more common and more serious in patients on etanercept.
Live vaccines should not be given during treatment with etanercept. Ensure all vaccinations are up to date before starting etanercept treatment. If vaccines become essential, the etanercept should be discontinued for one to two months prior to vaccination and restarted several weeks afterwards.
Etanercept should not be started during pregnancy (category B2) or breast feeding.
Screening tests prior to etanercept
Screening tests recommended prior to starting etanercept usually include full blood count, liver enzymes, serum creatinine, urine analysis, pregnancy test if relevant (urine or serum), HBV/HCV, HIV.
Tuberculosis screening includes chest X-ray, and Mantoux intradermal test or QuantiFERON-TB Gold blood test.
Side effects and risks of etanercept
Etanercept appears to be very well tolerated. Mild to moderate injection site reactions (redness, swelling, itching, pain) appear to be the most common side effect. These tend to occur in the first month and then become less frequent. Cool compresses and 1% hydrocortisone ointment may help to alleviate injection site discomfort. Some people complain of itchy skin generally and weight gain has been reported.
If any of the following symptoms or signs are severe or do not go away you should contact your doctor.
- Coughing, wheezing, breathlessness or chest pain
- Nausea and/or vomiting and/or abdominal pain
- Fever, headache, chills or other signs of infection
- Hot, red, swollen area on the skin
- Bleeding or bruising
- Unexpected weight loss
- Sore eyes (uveitis has been described as a possible uncommon adverse reaction to etanercept).
Severe cutaneous reactions have rarely been reported, including urticaria, angioedema, anaphylaxis and Stevens Johnson syndrome / toxic epidermal necrolysis.
Patients treated with etanercept may be at slightly greater risk of lymphoma and possibly other malignancies but these have been rarely reported. In most cases, the patients have also been taking other medicines that suppress the immune system such as azathioprine or mercaptopurine.
Other conditions that have been reported in patients on etanercept include demyelinating diseases such as multiple sclerosis (MS), cardiac failure and bone marrow suppression.
For more detailed information about etanercept, refer to current Enbrel datasheet.
- Goffe B, Cather JC. J Am Acad Dermatol 2003;49:S105-11.
- Sterry W, Ortonne JP, Kirkham B, Brocq O, Robertson D, Pedersen RD, Estojak J, Molta CT, Freundlich B. Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial. BMJ. 2010 Feb 2;340:c147. doi: 10.1136/bmj.c147. PubMed PMID: 20124563.
- Strohal R, Puig L, Chouela E, Tsai TF, Melin J, Freundlich B, Molta CT, Fuiman J, Pedersen R, Robertson D. The efficacy and safety of etanercept when used with as-needed adjunctive topical therapy in a randomised, double-blind study in subjects with moderate-to-severe psoriasis (the PRISTINE trial). J Dermatolog Treat. 2013 Jun;24(3):169-78. doi: 10.3109/09546634.2012.658015. Epub 2012 Feb 23. PubMed PMID: 22251226.
On DermNet NZ:
- Enbrel travel letter re cold chain: to be signed by prescribing doctor (PDF file)
- Biological response modifiers
- Psoriatic arthritis
- Consumer medicine information – Medsafe
- Enbrel data sheets – Medsafe
- Drugs, Herbs and Supplements – MedlinePlus
- Etanacept – British Association of Dermatologists
- Enbrel – manufacturer website (New Zealand)
- Enbrel injection videos – Pfizer website
Books about skin diseases:
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The New Zealand approved datasheet is the official source of information for this prescription medicine, including approved uses and risk information. Check the New Zealand datasheet on the Medsafe website.