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Value of the HLA-DRB1 Shared Epitope for Predicting Radiographic Damage in Rheumatoid Arthritis Depends on the Individual Patient Risk Profile
A. CECILE J.W. JANSSENS, EWOUT W. STEYERBERG, YEBIN JIANG, J. DIK F. HABBEMA, CORNELIA M. VAN DUIJN, and LINDSEY A. CRISWELL ABSTRACT. Objective. To investigate the influence of individual patient risk profiles on the value of the HLA-DRB1 shared epitope (SE) as a predictor of severe erosive damage in rheumatoid arthritis (RA). Methods. Patient characteristics, clinical signs and symptoms, rheumatoid factor (RF) status, and HLA-DRB1 genotypes were available for 154 Caucasian women with RA. Risk profiles were defined by non-genetic factors that predict severe erosive disease. The additional value of the SE was defined by the likelihood ratios (LR) of SE presence and absence, which were calculated at the individual patient level. Results. In the total population, the LR of SE presence was 1.42 and the LR of SE absence was 0.37, corresponding to an odds ratio of 3.9, indicating a substantially higher risk of severe erosive disease in those with the SE compared to those without. The LR of SE presence and absence varied depending on the risk profile of the women, from 1.01 to 2.25 for SE presence and 0.22 to 0.49 for SE absence. Considering all the patient characteristics, SE status was most significantly related to RF status. Consequently, the LR of SE presence and absence were higher for RF-negative women compared to RF-positive women (SE presence 1.77 vs 1.40, p < 0.001 and SE absence 0.38 vs 0.30, p < 0.001). Conclusion. The additional value of SE testing for predicting severe erosive disease varies according to patient risk profiles. Given the likely availability of genetic and other novel tests in the future, information about the additional value of test results is needed to ensure the optimal use of such testing in the management of RA. (First Release Sept 1 2006; J Rheumatol 2006;33:2383-9) Key Indexing Terms:
RHEUMATOID ARTHRITIS From the Departments of Public Health and Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; and the Departments of Radiology and Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, California, USA. Supported by NIH P60 AR20684 and K24 AR02175, and by the Netherlands Organization for Scientific Research (NWO; grant number 945-10-039). A.C.J.W. Janssens, PhD, Postdoctoral Researcher; E.W. Steyerberg, PhD, Associate Professor of Clinical Decision Sciences; J.D.F. Habbema, PhD, Professor of Clinical Decision Sciences, Department of Public Health; C.M. van Duijn, PhD, Professor of Genetic Epidemiology, Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam; Y. Jiang, MD, PhD, Associate Professor of Radiology, Department of Radiology; L.A. Criswell, MD, MPH, Professor of Medicine, Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco. Address reprint requests to Dr. L.A. Criswell, University of California, San Francisco, Division of Rheumatology, 374 Parnassus Avenue, Box 0500, San Francisco, CA 94143-0500, USA. E-mail: Lindsey.Criswell@ucsf.edu
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