Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Enbrel (Wyeth)
vials containing 25 mg
Approved indication: rheumatoid arthritis
Australian Medicines Handbook Section 15.2.2
The treatment of rheumatoid arthritis now involves the early use of disease-modifying antirheumatic drugs. Despite early intervention some patients will continue to have joint inflammation. Researchers have therefore been investigating how to control the cytokines involved in the inflammatory process.
Tumour necrosis factor is a cytokine found in the synovium. It stimulates cell proliferation and the production of inflammatory mediators. Etanercept blocks this action by binding to the receptors for tumour necrosis factor.
The etanercept molecule is a human tumour necrosis factor receptor fusion protein. It is produced by recombinant DNA technology.
Patients have to inject etanercept twice a week. After subcutaneous injection etanercept is slowly absorbed. It has a half-life of 70 hours, but the mechanism of elimination is unknown. There have been no pharmacokinetic studies to examine the effect of renal or hepatic impairment.
A double-blind placebo-controlled study enrolled 234 patients who had failed to respond to a disease-modifying antirheumatic drug. After six months of treatment59% of the patients given etanercept had a 20% improvement in their symptoms and signs. In the placebo group only 11% had a similar response.
Another study investigated adding etanercept to methotrexate therapy. After24 weeks 71% of the 59 patients taking the two drugs had at least a 20% improvement in their symptoms and signs. This was significantly greater than the response in the 30 patients taking methotrexate and placebo even though 27% of this group also improved.1
During the clinical trials etanercept was well tolerated, but there are post-marketing reports of serious adverse events. By inhibiting tumour necrosis factors etanercept may reduce the body's defences against infections and tumours. There were 22 serious infections and seven malignancies in 745 patients taking etanercept. Some patients with sepsis have died, so etanercept should be stopped if a serious infection develops. Extra caution is needed if etanercept is prescribed for patients who may have an increased risk of infection, for example patients with diabetes. Patients can develop auto antibodies, but no lupus-like reactions have been reported.
A common problem for patients is a reaction at the injection site. These reactions may be swelling, pain or itching and can last for several days. It is important that patients who are going to self-administer etanercept are instructed in how to prepare the injection. Other frequent adverse events include headache and upper respiratory infections.
When a patient stops injecting etanercept their arthritis usually returns within a month. At present, there is limited information about the long-term continuous use of etanercept. This therapy is likely to be very expensive and there is currently no method of predicting which patients will benefit from etanercept. It should be reserved for patients who have not responded to other drugs.
