Newer immunosuppressive drugs: their potential role in rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a chronic immune-mediated disease characterised by chronic synovitis, which leads to cartilage damage and joint destruction. It is generally a progressive disease with radiographic evidence of joint damage, functional status decline and premature mortality. Proinflammatory cytokines, such as interleukin 1 and tumour necrosis factor alpha, play an important role in maintaining the chronicity of RA and mediating tissue damage. New approaches in the therapy of RA with anticytokine biological agents, which neutralise or block cytokines or their receptors, are now the first generation antirheumatic drugs in clinical practice. A better understanding of the signal transduction systems and gene regulation by transcription factors involved in cytokine production has opened the way for the discovery of novel therapeutic compounds useful in treating patients with RA. Overactivation of selective kinases or aberrant function of downstream transcription factors could help convert a normal immune response to a chronic disease state. This provides a unique opportunity for novel therapeutic interventions, since specific signal transduction or transcription factor targets might interrupt the perpetuation mechanisms in RA. The availability of potent and selective p38 mitogen activated protein kinase inhibitors provide a means in further dissecting the pathways implicated in cytokine production, which in turn maintain the chronicity of RA. Many studies conclude that these compounds are very useful in the treatment of chronic synovitis and therefore are very promising for RA treatment.