Etanercept, an anti-tumour necrosis factor (TNF) drug, is likely to be launched early next year for the treatment of rheumatoid arthritis, according to a spokesman for its manufacturer, Wyeth.
However, the position in therapy of anti-TNF drugs would depend on further large clinical trials, said Professor Paul Bacon (department of rheumatology, University of Birmingham) at a Wyeth-sponsored press briefing on arthritis management on October 20.
In the US, etanercept is licensed for patients who have failed on disease modifying anti-rheumatic drugs (DMARDs). Wyeth says that a similar licence has been applied for in the UK. Professor Bacon said that he would like to see anti-TNF drugs used in earlier stages to "stop the disease in its tracks". However, trials so far had concentrated on late stage disease, so further studies would be needed.
Professor Bacon explained that TNF was a cytokine involved in the inflammatory cascade. Although TNF was an essential component of the immune system, people with rheumatoid arthritis had an excess of it. TNF stimulated a number of other cytokines, which resulted in inflammation in the joint. It also stimulated the production of interleukin-1 (IL-1) which drove pro-inflammatory cytokines. Therefore, blocking TNF would reduce inflammation by the direct and indirect (through IL-1) blockage of pro-inflammatory cytokines.
TNF could be blocked by two methods. Antibodies which specifically recognised TNF had been developed (eg, infliximab [not yet launched]). Alternatively, soluble TNF receptors could be used to "mop up" and therefore inactivate the excess TNF. The soluble receptors were stabilised by linking two together to form etanercept. Both types of anti-TNF drug are given by injection.
Professor Bacon said that there was no hard answer as to the advantages of one type of anti-TNF therapy over the other. There was no evidence of efficacy differences between the two methods of blocking TNF.
The main adverse effects of anti-TNF drugs that had caused problems were local reactions at the injection site and the body's own immune response to the anti-TNF antibodies, Professor Bacon said. There were concerns that treatment might increase the risk of infection but there had not been any significant increases in infection in any studies so far. However, "there is understandable caution about using anti-TNF therapy in patients [such as the immunodepressed] with any risk of infection," he said.
In the US, the Food and Drug Administration has reported that infections and sepsis have been seen in patients taking etanercept. Wyeth said that the number of cases was not beyond the levels expected because the majority of patients taking etanercept were elderly and more prone to infection.
Professor Bacon added that the dose of an anti-TNF drug would have to be carefully titrated for individuals because TNF was essential in the immune system response. The dose would have to be such that an overblocking of TNF did not occur.
Dr John Dickson (general practitioner, Yorkshire and member of the Primary Care Rheumatology Society) said that an advantage of anti-TNF therapy over DMARDs was that no monitoring was required. Patients treated with DMARDs often require regular blood, urine, liver and kidney monitoring.