Etanercept (Enbrel), an anti-tumour necrosis factor (TNF) drug, is now available for the treatment of rheumatoid arthritis.
Etanercept is licensed for the treatment of active rheumatoid arthritis in adults when the response to disease modifying antirheumatic drugs, including methotrexate, has been inadequate. It is also licensed for the treatment of polyarticular-course juvenile chronic arthritis in children aged four to 17 years who have had an inadequate response to, or who have been proved intolerant of, methotrexate.
When first licensed, in February, the manufacturer, Wyeth Laboratories, indicated that the drug would only be available for paediatric patients because of a shortage of supplies.
The supply situation has now improved. Mr David Gibbons (corporate affairs executive, Wyeth) told The Journal on May 16 that etanercept was now also available for adults. Supplies would still be limited in the "short to medium term" but Wyeth expected that supplies of etanercept during 2000/2001 "will be sufficient to satisfy a significant proportion of the patients for whom health authority funding is anticipated." Now that the company was sure that it had secure supplies of etanercept, promotion of the product would be starting, Mr Gibbons said.
Treatment with etanercept costs around £650 a month.
TNF is involved in the inflammatory process (see PJ, November 6, 1999, p737). Etanercept is a soluble receptor - it is a synthesised version of the human TNF receptor, which acts by binding to TNF before the cytokine can bind to the TNF receptor sites on cells. Another anti-TNF drug, currently licensed for use in Crohn's disease, is infliximab which is an antibody to TNF. The manufacturer of infliximab (Remicade), Schering-Plough, has applied for a licence for its use in rheumatoid arthritis.
Clinical trials At the British Society for Rheumatology conference in Brighton on May 9, Dr Barry Bresnihan (consultant rheumatologist, St Vincent's hospital, Dublin) gave an update lecture on the use of anti-TNF drugs in rheumatoid arthritis. He said that in clinical trials the drugs had shown impressive results in terms of preventing progression of joint damage. However, not all patients responded to treatment and it would be important to learn how to identify likely responders. There had been few serious side effects from the anti-TNF therapies in clinical trials but careful postmarketing surveillance would be needed to check the safety of long-term TNF blockade.
Dr Bresnihan explained that the rationale for treatment was that TNF had a key position in the hierarchy of pro-inflammatory mediators in RA, its production was increased in RA, and it was involved in interleukin-1 (IL-1) production.
One possible explanation as to why not all patients responded fully to treatment had become apparent in recent research which found that, although treatment led to a reduction in TNF-producing cells, in some patients IL-1 production in the synovial fluid was unaffected. This suggested that TNF was not the only factor regulating IL-1 production in RA. It might be, said Dr Bresnihan, that combinations of different biological therapies would be needed for optimum results.