Recent developments in the treatment of rheumatoid arthritis with targeted biological agents

Abstract

Rheumatoid arthritis RA is a chronic systemic autoimmune inflammatory disease characterised by progressive joint damage. The pathophysiological processes involved in inflammatory reactions such as occur in RA and during infections have now been delineated, providing a scientific rationale for the use of biological and/or chemical entities targeted at specific sites of the inflammatory cascade in order to modulate inflammation. Currently available therapies for RA, such as myocrisin and sulfasalazine, were developed empirically without much regard for the basic physiological mechanisms of inflammation, and are not always effective at controlling the disease. The majority of the novel agents being developed for the treatment of RA are biological. However, their clinical effects have been transient, necessitating repeated treatments, many have to be administered parenterally, production costs are very high and some patients have developed antiglobulin responses. Consequently, chemical entities that can be taken orally have been developed. Clinical trials are awaited. Since the immune system is so complex, with pleiotropic cytokines and apparent redundancy in some of the regulatory networks, successful treatment of RA may require the administration of multiple agents targeted at different specific sites of the inflammatory cascade, or of different agents at different stages of the disease, in order to induce disease remission and maintain the response to therapy. However, since cytokines such as TNF-a and IL-1 play important physiological roles in the host's defence systems, chronic inhibition of these cytokines by targeted therapies may be associated with unwanted effects, e.g., infections. Long-term, carefully controlled studies are therefore necessary to assess the safety of selective targeting of processes involved in inflammation. In this chapter the current status and future prospects of these novel and advanced treatment modalities for RA are reviewed.