Our long-term goal is to improve health outcomes in patients with gout, the most common inflammatory arthritis in adult men. Inability to achieve a target serum urate of <6 mg/dl is common in gout patients undergoing treatment with urate-lowering therapy, which is associated with more acute gout flares, higher societal costs, and diminished quality of life. High-quality national studies of gout have been limited by the lack of availability of serum urate results in large national databases and use of only ICD-9 codes to identify gout cohorts, and when used alone ICD-9 codes may be inaccurate. Innovations in Veterans Affairs (VA) informatics including Natural language processing (NLP) algorithms, ability to obtain serum urate in national VA databases and to merge inpatient, outpatient and pharmacy databases allow conduct of high quality studies in gout. Data regarding patient, physician and healthcare factors influencing the ability to achieve target serum urate <6 mg/dl are lacking. Major adverse events (AEs) such as allopurinol hypersensitivity syndrome (AHS) and colchicine-associated neuromyopathy and hematologic AEs are associated with significant morbidity and mortality and have not been studied with well-designed, adequately-powered studies The main objective of this proposal is to study the effectiveness an safety of gout medications using national VA databases. Our project is innovative in using NLP algorithm to develop a large valid national cohort of gout patients, extracting serum urate levels and validating and studying AEs in a large gout cohort.
Specific Aim 1 : To identify key patient, provider, and health system factors associated with achieving and maintaining serum urate below 6 mg/dl (""""""""target"""""""") in gout patients taking allopurinol.
Specific Aim 2 : To characterize the epidemiology and risk factors for major adverse events (AEs) associated with the use of allopurinol and colchicine for treatment of gout. We will use natural language processing (NLP) algorithm that incorporates the rich information from national VA EHR (text field data from clinic notes) and nationally available laboratory results (serum urate, synovial fluid result) in addition to lCD-9 codes to more accurately identify gout patients. With a similar approach, we will identify a validated cohort of gout patients with major AEs. We will examine association of key (patient, physician, healthcare) factors with ability to achieve target serum urate and with risk of major AEs.

Public Health Relevance

This translational research will improve our understanding of clinical and healthcare factors affecting optimal serum urate lowering in patients with gout receiving treatment with allopurinol, which is associated with improved quality of life, less activity limitation, lower risk of acute attacks and less health care costs. We will also fill the knowledge gap related to the frequency of major AEs and identify key factors associated with increased risk of AEs. Knowledge gained from this study will lead to improved health outcomes in gout.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1-KM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
United States
Zip Code
Ryan, Evan M; Duryee, Michael J; Hollins, Andrew et al. (2018) Antioxidant properties of citric acid interfere with the uricase-based measurement of circulating uric acid. J Pharm Biomed Anal 164:460-466
Melles, Ronald B; Jorge, April M; Marmor, Michael F et al. (2018) Sharp decline in hydroxychloroquine dosing-analysis of 17,797 initiators from 2007 to 2016. Clin Rheumatol 37:1853-1859
Bursill, David; Taylor, William J; Terkeltaub, Robert et al. (2018) Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions for disease elements in gout. Arthritis Care Res (Hoboken) :
Jorge, April; Wallace, Zachary S; Zhang, Yuqing et al. (2018) All-Cause and Cause-Specific Mortality Trends of End-Stage Renal Disease due to Lupus Nephritis from 1995 to 2014. Arthritis Rheumatol :
Choi, Hyon; Neogi, Tuhina; Stamp, Lisa et al. (2018) New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert. Arthritis Rheumatol 70:1702-1709
McWherter, Charles; Choi, Yun-Jung; Serrano, Ramon L et al. (2018) Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. Arthritis Res Ther 20:204
Sun, Mengying; Vazquez, Ana I; Reynolds, Richard J et al. (2018) Untangling the complex relationships between incident gout risk, serum urate, and its comorbidities. Arthritis Res Ther 20:90
Mikuls, Ted R; Cheetham, T Craig; Levy, Gerald D et al. (2018) A Pharmacist-Led Intervention to Improve Gout Medication Adherence and Outcomes with Urate Lowering Therapy: A Site Randomized Trial. Am J Med :
Johnson, Tate M; Register, Kyle A; Schmidt, Cynthia M et al. (2018) Correlation of the Multi-Biomarker Disease Activity Score with Rheumatoid Arthritis Disease Activity Measures: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken) :
England, Bryant R; Thiele, Geoffrey M; Anderson, Daniel R et al. (2018) Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. BMJ 361:k1036

Showing the most recent 10 out of 57 publications