Insights and Implications of the VA Rheumatoid Arthritis Registry
The VA Rheumatoid Arthritis Registry addresses the underrepresentation of veterans in rheumatoid arthritis research, serving as a repository that links banked serum, plasma, and DNA samples with an array of patient-level information.
Dr. Mikuls is a staff rheumatologist and research scientist at the VA Nebraska Western-Iowa Health Care System and the Umbach Professor of Rheumatology at the University of Nebraska Medical Center, both in Omaha. Dr. Reimold is chief of the Rheumatology Section at the Dallas VAMC and associate professor at the University of Texas Southwestern Medical Center, both in Dallas. Dr. Kerr is chief of the Division of Rheumatology at the Washington DC VAMC and professor of medicine at Georgetown University, both in Washington, DC. Dr. Cannon is associate chief of staff at the George E. Wahlen VAMC and professor of medicine in the Division of Rheumatology at the University of Utah, both in Salt Lake City.
Rheumatoid arthritis (RA) is a systemic autoimmune disease that manifests primarily in the joints, leading to substantial morbidity, reduced survival, and enormous health care costs. As a result, RA exerts a major impact on patients and health care systems. U.S. military veterans and active-duty personnel have traditionally been underrepresented in RA research, likely due in part to the challenges posed by conducting investigations across federal facilities or the common refrain that such populations are not generalizable to the demographic groups (eg, younger women) most prone to develop RA.
Although RA is 3 to 4 times more common in women than in men (the latter comprising about 90% of the U.S. veteran population), its relevance to the VA health system has grown with the increase in women veterans. Well-defined risk factors for RA, such as cigarette smoking, are highly prevalent in these populations, as are comorbid conditions that frequently complicate its disease course, most notably cardiovascular disease.1 Men with RA, a disease demographic common in the VA, seem to experience a more severe disease arthritis course than do women with RA and more commonly have extra-articular manifestations, which are known to contribute to worse outcomes.2 Yet, data from predominantly male RA cohorts are sparse.
To address this gap in RA research, the VA Rheumatoid Arthritis Registry (VARA) was established in 2002 with its first patient enrolled in early 2003. Since its early inception, the registry has served as a research resource not only for VA investigators, but also for their collaborators, the VA health system, and U.S. veteran patients. This report reviews the resources available in VARA, the important insights gained in these efforts, and implications for both patients and health systems providing care. Future directions and opportunities for VARA and other disease registries are provided.
Registry Background
The VARA is a prospective, observational, multicenter study that includes VAMCs in 12 cities (Birmingham, Alabama; Brooklyn, New York; Dallas, Texas; Denver, Colorado; Jackson, Mississippi; Iowa City, Iowa; Little Rock, Arkansas; Omaha, Nebraska; Portland, Oregon; Philadelphia, Pennsylvania; Salt Lake City, Utah; and Washington, DC). In addition to support from VA research, this multicenter effort has been supported by the VA Office of Research Development, the National Institutes of Health, industry, and nonprofit foundations. The VARA serves as a repository linking banked serum, plasma, and DNA samples with an array of patient-level information, including sociodemographics, medical history, medications, comorbid conditions, longitudinal disease activity measures, and other variables (eFigure).
Clinical data are entered by investigators during routine rheumatologic care, facilitated by the use of standardized patient note templates in the VA Computerized Patient Record System, semi-automated data abstraction, and a secure intranet-based platform. With regulatory approvals, including approval of the VARA Scientific and Ethics Advisory Committee (SEAC), registry data are accessed using the VA Informatics and Computer Infrastructure (VINCI), allowing for secure linkage with detailed administrative data, including medication dispensing, diagnostic and procedural codes, and vital status.
The VARA includes > 2,200 veteran patients, all having provided informed consent, aged ≥ 18 years at disease onset, and satisfying the American College of Rheumatology (ACR) classification criteria for RA (Table 1). Serum, plasma, and DNA samples are collected at enrollment and banked in a central biorepository housed at the Nebraska Western-Iowa VA Health Care System in Omaha. In addition to providing ethical and scientific review, the VARA SEAC also provides oversight for biospecimen access. Upon receipt of specimens, the central biobank performs standardized laboratory assays on serum, including C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated (anti-CCP) antibody. These data are made available for all future investigations.
Vara Research Insights
The VARA has served as a valuable resource for a wide scope of clinical and clinical-translational research, ranging from studies of disease outcomes and their determinants, genetic and environmental risk factors, the validation of biomarkers, and health care resource utilization, among others (Table 2).
Mortality and Morbidity
The VARA researchers observed a more than 2-fold increase in mortality risk among men with RA compared with age-matched men without RA in the general U.S. population (standardized mortality ratio [SMR] 2.1; 95% confidence interval, 1.8-2.5), a risk that seems to be higher than that observed in other RA cohorts.3 Of the variables associated with mortality in this group, several potentially modifiable factors can be identified, including high erythrocyte sedimentation rate (ESR); elevated Disease Activity Score (DAS)-28 (a composite measure of disease activity including assessments of 28 joints); prednisone use; and low body weight. Patients with a body mass index < 20 kg/m2 (considered underweight) had an SMR > 5.0. Based on more recent VARA evaluations, this association seems to be driven primarily by prior weight loss rather than absolute body weight.4
