Section Review Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: The current status and future prospects for biological targeted therapies for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease which leads to progressive joint damage. Currently available therapies, such as myocrisine and sulphasalazine, were developed empirically without much regard for the basic physiological mechanisms of inflammation and are not always effective at controlling the disease. The pathophysiological processes involved in the inflammatory reactions that occur, for example, in RA and during infection, have now been delineated, thus, 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. The majority of these agents are biological and clinical trials in RA are in progress. Although the results obtained in some of the studies using single agents have been encouraging, the clinical effects have been transient, necessitating repeated dosing. This, along with the requirement for intravenous administration for many of these agents, the high production costs and the occurrence of antiglobulin responses in a number of patients, has fueled the development of chemical entities that can be administered orally and that are directed at specific cellular targets; clinical trials are awaited. Since the immune system is very complex with pleiotropic cytokines and apparent redundancy in some of the regulatory networks, in order to induce disease remission and maintain the response to therapy, it may be necessary to use multiple agents targeted at different specific sites of the inflammatory cascade or different agents at different stages of the disease. Cytokines such as TNF-α and IL-1 play important physiological roles in the host's defence systems. Hence, chronic inhibition of these cytokines by targeted therapies may be associated with unwanted effects such as infection. Long-term, carefully controlled studies are necessary to assess the safety of selective targeting of processes involved in inflammation. Finally, attempts at controlling chronic inflammation have been made by inducing immune tolerance using orally ingested biological preparations, such as bacterial extracts and collagen. This paper reviews the current status and future prospects of these novel modalities for modulating rheumatoid inflammation.