The traditional approach to the treatment of
rheumatoid arthritis (RA) has been the use of nonsteroidal anti-inflammatory drugs usually in combination with a
disease-modifying antirheumatic drug (
DMARD) such as
hydroxychloroquine,
gold,
sulfasalazine,
methotrexate,
leflunomide or
cyclosporin. Each of these DMARDs has its own distinct toxicities but has also been shown to be effective in reducing signs and symptoms of disease and to some extent, reduce radiological progression. Within the past 10 years, the combination of several traditional DMARDs has been shown to have increased efficacy over monotherapy without a significant increase in toxicity in a majority of studies. Recently, the US Food and Drug Administration has approved
infliximab, a chimeric
monoclonal antibody to tumour
necrosis factor (
TNF)-alpha in combination with
methotrexate, for the treatment of signs and symptoms of RA, delay of radiological progression of disease and improvement of physical function while
anakinra, an
interleukin-1 receptor antagonist, has been approved for the treatment of the signs and symptoms of RA either as monotherapy or in combination with
methotrexate.
Etanercept is the first
biological response modifier approved for use in RA in the US. Double-blind, randomised controlled studies have shown
etanercept to be effective
therapy in patients with RA who have had inadequate response to DMARDs, in combination with
methotrexate, and as early monotherapy. Similar results were seen in juvenile and
psoriatic arthritis in
DMARD nonresponders. Open-label studies have shown efficacy in adult Still's disease,
ankylosing spondylitis,
progressive systemic sclerosis,
Wegener's granulomatosis and chronic
uveitis. Safety issues are a concern because of the ubiquitous role of TNF. To date the only consistent adverse event seen with
etanercept has been
injection site reactions.
Infections occur at the same rate and with the same frequency as the placebo population. There should be caution, however, with using
etanercept in patients with a serious
infection, or
recurrent infections or patients with untreated or
latent tuberculosis. As of yet there has not been seen an increase of
malignancies. Rare neurological and haematological events have been noted.
Etanercept has been a significant addition to the armamentarium of medications for the treatment of RA, juvenile and
psoriatic arthritis. Preliminary data show that it may be well tolerated and effective in other
rheumatic diseases in which there is over production of
TNFalpha.