Cytokine inhibitors in the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated disease characterised by articular inflammation and subsequent tissue damage leading to severe disability and increased mortality. A variety of cytokines are produced locally in the rheumatoid joints. Numerous studies have demonstrated that IL-1 and TNF-alpha, two prototypic pro-inflammatory cytokines, play an important role in the mechanisms involved in synovial inflammation and in progressive joint destruction. Indeed, the administration of TNF-alpha and IL-1 inhibitors in patients with RA led to a dramatic improvement of clinical and biological signs of inflammation and a reduction of radiological signs of bone erosion and cartilage destruction. However, despite these encouraging results, a significant percentage of patients do not respond to these agents, suggesting that other mediators are also involved in the pathophysiology of arthritis. This review describes the results of clinical trials with TNF-a inhibitors and a specific IL-1 inhibitor (IL-1 receptor antagonist [IL-1Ra]). In addition, other therapeutic strategies are also discussed.