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Wednesday, 20 October 2004 - 11:00 AM

This presentation is part of: Oral Concurrent Session A - Clinical Strategies and Guidelines

CLINICAL PREDICTORS DETERMINE THE VALUE OF GENETIC TESTING IN THE PREDICTION OF SEVERE PROGNOSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

A. Cecile J. W. Janssens, PhD1, Ewout W Steyerberg, PhD1, Cornelia M Van Duijn, PhD2, and Lindsey A. Criswell, MD, MPH3. (1) Erasmus MC, Department of Public Health, Rotterdam, Netherlands, (2) Erasmus MC, Department of Epidemiology and Biostatistics, Rotterdam, Netherlands, (3) University of California, San Francisco, Department of Medicine, San Francisco, CA

Objective: Genetic factors influence disease progression, but may also predispose to other, non-genetic, predictors of prognosis such as age at onset and severity of early symptoms. The additional value of genetic information to the prediction of prognosis may therefore differ in the presence or absence of these clinical predictors. We aim to evaluate the additional value of HLA-DRB1 alleles encoding the rheumatoid arthritis (RA) shared epitope (SE) in predicting radiographic damage in RA conditional on non-genetic predictors.

Methods: Demographic characteristics, baseline clinical characteristics and SE status were available for 180 Caucasian women with RA. Univariate analyses were performed for the selection of non-genetic predictors. The additional value of the SE to the prediction of radiographic damage was determined by a newly developed method estimating the likelihood ratio (LR) of SE status conditional on other predictors. These LRs were used to calculate the sensitivity and specificity of the SE testing for each woman in the study.

Results: Overall, the LR of SE presence (LR+) was 1.4, the LR of SE absence (LR-) 0.4, the odds ratio (OR) 4.0, sensitivity 0.85 and specificity 0.40. The SE was a significant predictor of radiographic damage (multivariate OR 5.1 [95% CI 1.9, 14.2]), next to Health Assessment Questionnaire (HAQ) score (OR 4.6 per 1.0 point [1.9, 11.0]), rheumatoid factor (RF) positivity (OR 5.4 [1.7, 16.8]) disease duration (OR 1.5 per 5 years [1.1, 1.9]) and family income (OR 0.8 per 1000 US$ [0.6, 1.0]). Of these predictors, HAQ score (p = 0.03) and RF positivity (p < 0.001) were also associated to the SE. At the individual patient level, taking into account the risk profiles of individual women, the LR+ varied from 1.0 to 2.3, the LR- from 0.2 to 0.5, the sensitivity from 0.60 to 1.00 and the specificity from 0.00 to 0.78. In women who were RF positive, the average LR+ and LR- were 1.5 and 0.3, and the average sensitivity and specificity were 0.89 and 0.36, whereas in those were RF negative, these figures were 1.9, 0.4, 0.78 and 0.57.

Conclusion: The value of genetic information in the prediction of prognosis depends on the risk profile of the patient. This variation is explained by correlation between the genetic factor and clinical predictors.


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