Pro-inflammatory cytokines in rheumatoid arthritis: pathogenetic and therapeutic aspects.

Therapy of rheumatoid arthritis (RA) aims at interfering with the disease process, namely inflammation and destruction of the joints, and thus at preventing long-term disability. Proinflammatory cytokines play a decisive role in the generation of the inflammatory and destructive response. Aside from traditional disease-modifying anti-rheumatic drugs and tumor necrosis factor-blocking agents, a number of targeted therapies are currently in evaluation, such as abatacept (interfering with co-stimulation), rituximab (an anti-B-cell agent) and tocilizumab (an anti-interleukin-6 receptor antibody). In phase II trials, all these agents have resulted in significant clinical improvement, and phase III trials have been partly completed with similar results and are partly on the way. Because none of these agents lead to good clinical responses in all patients and many patients have only relatively low degrees of response, it will still be a challenge to find the best therapeutic paths to combat the "inflammatory house of cards" of RA.