Cytokines as Targets for Anti-inflammatory Agents

Well over a decade ago a central role of tumor necrosis factor (TNF) was first described in patients with rheumatoid arthritis (RA) when remarkable clinical benefit was demonstrated in patients with refractory disease were treated with using either a monoclonal antibody or a soluble receptor fusion protein. There are now five anti-TNF agents approved by regulatory agencies for treating RA. Identifying which RA patients will have a meaningful clinical response (improvement in outcomes measures such as ACR 20, DAS score, remission, etc.) when used as monotherapy, or in combination with other immunosuppressive agents remains a major research effort. Also, attention has focused on the potential adverse events that can be seen with these therapies; an increase in opportunistic infections being the most clearly linked adverse event. These anti-TNF therapies have revolutionized the clinicians' ability to make a significant impact in RA, a disease that has significant excess morbidity and mortality.