ANTIBODIES TO CITRULLINATED HUMAN FIBRINOGEN PREDICT RADIOGRAPHIC PROGRESSION IN EARLY ARTHRITIS

Background: The anti-cyclic citrullinated peptide (anti-CCP) test is a good predictor for radiographic progression in early (rheumatoid) arthritis, however the cyclic citrullinated peptide is not the physiological target of the autoantibodies. Since citrullinated fibrin is abundantly present in the inflamed synovium, we assessed the prognostic value of antibodies against citrullinated fibrinogen (ACF), a soluble precursor of fibrin, in a group of early arthritis patients.Objectives: To assess the value of the ACF test for the prediction of radiographic progression in early arthritis.Methods: 379 patients (258 patients with rheumatoid arthritis (RA) and 121 patients with undifferentiated arthritis (UA)) aged ≥ 18 years with peripheral arthritis of ≥ 2 joints and ≤ 2 years symptom duration, newly referred to the Early Arthritis Clinic, were included. Radiographic progression was defined as an increase of the Sharp/van der Heijde score of at least 5 between baseline and 2 years follow-up, the remainder was classified as mild. Multivariate logistic regression analysis was used to assess the prognostic value of the ACF test. Baseline variables that correlated with radiographic progression (p<0.10) were added to the models as independent variables. The ability of the logistic regression model to predict the radiographic progression was expressed in terms of sensitivity, specificity and accuracy.Results: The early arthritis population consisted of 69% women with a mean age at baseline of 56 years. Median increase of the Sharp/van der Heijde score was 0 (IQ-range 0 to 1) and 2 (IQ-range 0 to 14) for UA-patients and RA-patients, respectively. Baseline variables showing a statistically significant correlation with radiographic progression were ACF, anti-CCP, IgM-RF, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28), health assessment questionnaire (HAQ) score and Sharp/van der Heijde score at baseline (all p<0.001). Because of the high agreement of the ACF test and the anti-CCP test (kappa of 0.84), the anti-CCP test was not added as independent variable in the logistic regression model. Of all baseline characteristics, the ACF test was the best predictor for radiographic progression after two year follow-up (OR=12.1). The other independent variables in the model were Sharp/van der Heijde score (OR=1.1) and ESR (OR=1.02) at baseline. Similar results were obtained if anti-CCP was added to the model and ACF left out. The sensitivity, specificity and accuracy of the model to predict radiographic progression were 68.5%, 88.2% and 81.7%, respectively.Conclusion: The ACF test is a good test to predict radiographic progression in early arthritis, with a value similar to the anti-CCP test.Citation: , volume , supplement , year 2004, page Session: Advances in RA clinical picture