Small molecular therapies for rheumatoid arthritis: where do we stand?

Early aggressive treatment and utilization of targeted biological therapies for rheumatoid arthritis (RA) has dramatically improved patient outcomes. Even with this approach up to 50% of patients fail to achieve a significant clinical response and these therapies require subcutaneous injection or intravenous administration and are costly. Development of small molecules that can be administered orally has progressed and several are under investigation as potential treatments for RA. This manuscript will update the status of the small molecules under development.

This review summarizes the newer molecular protein kinase targets involved in signal transduction of inflammatory mediators and the development of inhibitors to these kinases. Additionally, the results of clinical trials evaluating these therapies will be reviewed.

Based on the results of randomized clinical trials there is significant likelihood that a small molecular therapy to kinases involved in proinflammatory cytokine production will soon be available in the clinic. The benefit/risk profile is presently being determined in multiple late phase clinical trials.