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.
Cigarette smoking is a well-known risk factor for RA, and emerging data, including preliminary results from VARA, suggest that smoking may render a detrimental impact on outcomes.25 Current or former smoking (observed in about 4 of 5 VARA enrollees) is associated with higher ACPA and RF levels, relevant because these autoantibodies are predictive of worse long-term outcomes, including the accrual of joint damage.24-26 Disease activity of VARA participants, measured with multiple clinical measures and an array of proinflammatory cytokines, was higher among current smokers and significantly lower in former smokers, with the former smoking group demonstrating disease activity levels approaching that of never smokers.24 In addition to its benefit in other chronic health conditions, these results suggest that smoking cessation may be a viable approach in ameliorating the systemic inflammatory effects of RA.
The economic and societal burden posed by RA is enormous and growing. A large proportion of this growth relates to the near exponential increase in direct treatment costs accompanying the emergence of highly effective biologic therapies. Capitalizing on direct links between the VARA and administrative databases maintained in VINCI (eFigure), a recent investigation focused on the use of agents targeting tumor necrosis factor (TNF).27 These efforts have shown that among the 3 most commonly prescribed TNF inhibitors, persistence on initial treatment is similar over time, although important differences exist across agents in the frequency with which patients with RA undergo dose escalation. Recognizing that several reports have demonstrated their cost-effectiveness in RA, annual VA costs for a course of anti-TNF therapy approximated $13,000 to $17,000 per patient treated, and higher costs did not seem to translate into improved patient outcomes.27
Several recent initiatives have been undertaken within the VARA with the goal of expanding the breadth and depth of research that it supports. Ongoing efforts will link VARA with data from the National Death Index, allowing for examinations of cause-specific mortality. Given the high frequency of VA beneficiaries receiving dual care outside the VA system, future links with datasets, such as those from Medicare, will be essential to assure a more optimal capture of relevant health outcomes. Indeed, in recent surveys, almost 1 in 2 VARA participants reported the receipt of dual care, which was most common in those aged > 65 years or receiving prior joint replacement surgery (Pascale Schwab, MD, written communication, April 1, 2015).
Efforts are underway to add other well-annotated specimens to the biorepository, such as synovial fluid and tissues obtained during routine care. The VARA investigators, under regulatory approvals, have begun to collect serum samples longitudinally to complement the prospective disease activity assessments already in place. Other efforts will include the full adoption of standardized patient note templates and transitioning data entry from a decentralized and semi-automated process to one that is centralized and fully automated. This change will reduce the resources required for site investigators and study personnel.
The VA health care system is the largest integrated health system in the U.S. and as such, represents an ideal setting for the investigation of chronic health conditions and patient outcomes. The assets and potential of this system have been at least partially borne out in VARA over the past decade and now extend to other rheumatic disease registries in the VA, including those focused on spondyloarthritis (PULSAR) and gout (Crystal registry). Together, these registries are poised to provide valuable information about these rheumatic conditions and will continue to serve as models for patient registries from other medical disciplines in the VA and elsewhere.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
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