Eugene William St. Clair

The main focus of my research is the pathogenesis and treatment of rheumatoid arthritis (RA). This work has been conducted using patient-oriented research methodologies in collaboration with basic scientists and other clinical investigators. A major area of interest has been the development of novel therapies for RA, which has primarily included studies of novel biologics. Another important area of investigation has been the possible role of nitric oxide in the pathogenesis of RA.

My research is conducted in our Clinical Trials Unit which is built around a staff of three clinical research coordinators and a collaborative relationship with Dr. William E. Wilkinson, a Ph.D. biostatistician. Our group has been involved in numerous clinical trials sponsored by the pharmaceutical industry. Another important project has been a study of doxycycline therapy in RA, which has been supported by the National Institutes of Health (NIH). Recently, we have
begun an epidemiologic study of SLE in collaboration with Glinda Cooper, an epidemiologist from the National Institutes of Environmental Health Services in the Research Triangle Park. The General Clinical Research Center, an NIH-supported facility, has frequently served as the site for our research.

The current biologic therapies under investigation in patients with RA include a peptide vaccine, IL-4, IL-10, and anti-tumor necrosis factor-à chimeric monoclonal antibody (anti-TNF). The peptide vaccine consists of a "shared HLA-DRB1 epitope", a short amino acid sequence common to the -chain of those HLA-DR molecules associated with RA. IL-4 and IL-10 are inhibitory cytokines that ameliorate arthritis in experimental animal models and are in the early stages of development as a possible treatment for human disease. The most promising of the novel biologics are those agents inhibiting TNF. Our center is now involved in a phase III clinical trial of anti-TNF in patients with RA, a study involving over 20 other sites in the United States and Europe. I am also principal investigator of an NIH-sponsored study investigating the treatment efficacy of doxycycline in RA and the ability of this antibiotic to suppress collagenase activity in vivo. The work involving nitric oxide has been supported by a Specialized Center for Research in RA (Barton F. Haynes, M. D., Principal Investigator). Other current studies include a clinical trial of DHEA in SLE, and the epidemiologic study of SLE, which is based in North and South Carolina and will examine the relationship between environmental exposures and the incidence of disease.

I have been a consultant for several pharmaceutical companies who are developing new therapies for RA. In addition, I have served as a consultant on NIH study sections for applications related to clinical trials of new anti-rheumatic therapies. I have also organized a Sjogren's Syndrome Clinic at Duke that attracts referrals from the southeastern part of the United States. I have also spoken at the Annual Scientific Meeting of the American College of
Rheumatology on subjects related to my research and clinical interests, including Sjogren's Syndrome, vasculitis, and autoantibodies. Finally, I am developing an investigator's network in the southeastern United States, which should provide the patient base and infrastructure to conduct large clinical trials in rheumatology.

Key words: rheumatoid arthritis, biologics, clinical trials, Sjogren's syndrome, systemic lupus erythematosus, nitric oxide