Therapeutic Areas

Rheumatoid Arthritis Overview

Eduard Gorina, MD
Eduard Gorina, M.D.
Clinical Development

Eduard joined Portola in May 2009 and is involved in the clinical development of several of Portola’s investigational drugs...

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Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints involving destruction of cartilage and bone caused by inflammatory mediators released from leukocytes. Immune function by leukocytes is largely controlled by Syk-dependent signaling through the antigen-specific B cell receptor (BCR) and Fc receptors. Specific inhibition of Syk has the potential to control B cell antibody response to antigen as well as downstream effecter function of leukocytes that are activated in response to immunoglobulin immune complex engagement of Fc receptors. Targeting Syk represents a multi-faceted approach to modulating immune function at several points of intervention, making it an ideal target for RA and a variety of other inflammatory and autoimmune diseases.

RA is often progressive and debilitating and affects nearly 2.1 million people in the United States. RA patients receive multiple drugs depending on the extent and aggressiveness of their disease. Most RA patients eventually require some form of disease modifying anti-rheumatic drug, or DMARD. DMARDs include methotrexate, an anti-cancer agent, and/or a variety of intravenously-delivered immunomodulatory agents (TNF inhibitors and co-stimulation inhibitors). Up to 30 percent of patients continue to be resistant to these approaches and even in those that respond, active disease resurfaces in a number of patients. In addition, a range of toxicities occur, including gastrointestinal complications, kidney damage, opportunistic infections and increased incidence of lymphoma. As such, there is a need to develop safer and more effective therapeutic strategies for RA.