Monoclonal antibody therapy in rheumatoid arthritis

Ernest H. S. Choy, Gabrielle H. Kingsley, and Gabriel S. Panayi 

Department of Rheumatology, King s College and St. Thomas Hospitals Medical and Dental Schools, Guy s Hospital, London SEl 9RT, U.K. 

Rheumatoid arthritis (RA) is the commonest inflammatoiy and destructive arthropathy in the world with a prevalence of 1000 per 100000. It is characterized by a chronic symmetrical polyarthritis that leads to joint damage in most patients. The commonest affeaed joints are the small joints of the hands and feet but it can involve any synovial joint. Rheumatoid fector is present in over 70% of the patients. The long-term prognosis of RA is poor as most patients develop significant disability despite treatment (1). Hence it is a major sodo-economical burden. In the UK, the cost of RA was estimated at 1.3 billion/year in 1992 (2). 

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A variety of medical conditions are now believed to be caused or exacerbated by overproduction of certain cytokines in the body. A variety of pro-inflammatory cytokines, including IL-6 and IL-8 as well as TNF, have been implicated in the pathogenesis of both septic shock and rheumatoid arthritis. Inhibiting the biological activity of such cytokines may provide effective therapies for such conditions. This may be achieved by administration of monoclonal antibodies raised against the target cytokine, or administration of soluble forms of its receptor which will compete with cell surface receptors for cytokine binding. 

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Another TNFa monoclonal antibody known as etanercept (a fusion protein of human IgG and two p75 TNF receptors) [98] that is a competitive inhibitor of TNF s cell-surface receptor has been developed. Clinical studies have shown that etanercept therapy results in significant clinical benefits and is well tolerated and safe for long-term use [99-101]. Etanercept is given subcutaneously (25 mg) twice weekly for the treatment of rheumatoid arthritis [98]. It is also used in the treatment of psoriatic arthritis, and a recent clinical trial has reported that in addition to decreasing joint pain and fatigue, etanercept also decreases symptoms of depression associated with this chronic disease [102]. 

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