Etanercept (Enbrel)
Professor Robert J Moots BSc (hons) MBBS (hons) PhD FRCP, Professor of Rheumatology, University Hospital Aintree, University of Liverpool
Original article: 24/08/2004
Reviewed: 22/01/2009
Next review due: 22/01/2012
Introduction to Etanercept (Enbrel)
Etanercept was specially designed to neutralise tumour necrosis factor alpha (TNFα), an important molecule produced during inflammation. It is given by an injection under the skin, once a week. In the past, it was given twice a week, in smaller doses.
Clinical Trials
Etanercept has now been used to treat RA for more than ten years. In 1997, Moreland reported in the New England Journal of Medicine that etanercept suppressed disease activity and relieved symptoms in patients with RA who had not responded to other conventional disease modifying drugs (DMARDs). Since then, numerous studies in the USA, Europe and other countries have confirmed that etanercept is very effective in RA – both in long-term disease and also in newly diagnosed early RA. Two good examples of major clinical trials studying the use of etanercept in RA are the TEMPO and COMET studies.
The TEMPO Study, reported in 2004 in the Lancet was a large, well-designed, double-blind international study. Patients with RA who had not responded to a previous DMARD were started on either methotrexate alone, etanercept alone, or a combination of the two. After a period of a year, it was clear that the combination of etanercept and methotrexate provided much better results - with almost 50% of people achieving an ACR 70 response and approximately 40% going into remission - such results were previously unheard of. During subsequent years of follow-up, these excellent responses were found to persist, without new side-effects developing. It was even more striking to observe that that the combination of etanercept and methotrexate appeared to stop worsening of x-ray changes in the joints – an effect that again persisted over the further years of study.
The first year data from the two year COMET study was reported in the Lancet in 2008. This compared standard treatment of methotrexate with the combination of etanercept and methotrexate in patients with early RA. Patients taking the combination of etanercept and methotrexate fared better than those on methotrexate alone – with as many as 50% going into full remission (and many more enjoying low disease activity). In addition, far fewer patients taking the combination of etanercept and methotrexate had to stop work during the year, compared to those on methotrexate alone.
Side-effects of Etanercept
Most people tolerate etanercept well. One of the most common side-effects of etanercept is an injection site reaction, but this becomes less common after the first month of treatment. However, as with the other TNFα inhibitor drugs, etanercept suppresses an important molecule that is produced in inflammation – whether due to infection or RA. This suppression of TNFα is responsible for the beneficial effects in reducing inflammation in RA, but also explains the more serious potential side-effects: an increased susceptibility to infection. Trivial infections may persist a little longer than normal in some people but, more importantly, more serious infections such as pneumonias and septicaemias (blood poisoning) may develop in others. The hundreds of patients receiving etanercept in clinical trials did not get any more serious infections than the patients taking methotrexate - however, experience in real-life, outside clinical trials, suggests that etanercept (like all of the other anti TNFα inhibitors) can make people more susceptible to infection. It is important for patients taking etanercept to contact their doctor, rheumatologist or rheumatology specialist nurse if they feel that they are starting with an infection and receive antibiotics if necessary.
As well as being important in fighting infection, TNFα is potentially important in the body’s defence against cancer. It is theoretically possible, therefore, that suppressing this chemical may result in a higher chance of developing cancer. However, over the many years of experience with etanercept and the other anti-TNFα drugs, there have been isolated reports, but not firm and consistent evidence for a greater incidence of cancer developing than would have been expected if patients were not taking this drug. This is something that registries, such as The British Society of Rheumatology Biologics Register will help answer. At present, whilst there is no strong evidence to suggest an increased risk of cancers or other tumours, rheumatologists are advised not to start this drug in patients who are currently being treated for, or have recently had, a cancer.
NICE approval
The UK National Institute for Health and Clinical Excellence (NICE) has approved the use of etanercept as a cost-effective therapy for RA (after failure or intolerance to two DMARDs including methotrexate and high disease activity), juvenile idiopathic arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis. Many other countries around the world allow etanercept and other TNFα inhibitors to be used in patients with less severe RA and also earlier in the course of the disease.
Other uses for Etanercept
Etanercept has also been shown to be effective in treating other inflammatory joint problems such as juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis and a range of other inflammatory problems including psoriasis.
References available on request
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