OP0013 MEASURING ANTI-CITRULLINATED PEPTIDE/PROTEIN SA AUTOANTIBODIES TO PREDICT RA JOINT DESTRUCTION
O Meyer, P Nicaise, B Combe, M Dougados, A Cantagrel, P Goupille, J Sibilia, H Menard

Two rheumatoid-specific autoantibodies, anti-citrullinated proteins (anti-CCP)/peptides and anti-Sa, have recently been described. Sa antigen is present in the synovium of 31-43% of patients with established rheumatoid arthritis (RA), however, is present in only 20-25% of patients with early RA. The objective of this study was to determine the prevalence of anti-Sa compared to anti-CCP and the prognostic value of both to predict articular damage.

Methods: 191 patients with RA onset of < 12 months who had not received any DMARD treatments were prospectively followed for 5 years. X-rays of hands and feet were obtained at baseline, 3 and, 5 years. Radiographic joint damage was assessed using the modified Sharp score. Serum IgM RF, anti-CCP (ELISA), and anti-Sa (Western blot and ELISA) were measured.

Results: At baseline, RF+, anti-Sa, and anti-CCP were present in 69%, 28%, and 55% of patients, respectively. The following table compares the 5-year modified Sharp scores with the presence or absence of anti-Sa and anti-CCP.

All patients were treated with DMARDs during the study period, which did not appear to affect the persistence of anti-CCP antibodies. Based on multivariate analysis, a positive anti-CCP antibody test contributed significantly (OR 2.39 [95%CI 1.14-4.99] p=0.09) in predicting destructive RA 5 years later. This was not the case for Anti-Sa antibody positivity.

Conclusion: Anti-CCP has a higher prevalence than anti-Sa in early RA. Additionally, a positive anti-CCP antibody test can serve as a prognostic marker for more frequent and severe radiographic progression.

Editorial Comment: There is now significant information showing that early, aggressive treatment improves long- term outcomes of patients with rheumatoid arthritis. Tools for early diagnosis and tools that predict poor outcomes have become increasingly important to guide the choice of therapy. Although this study shows that having a positive anti-CCP antibody increases your risk of joint erosion, the overall predictive value of the test is small with an odds ratio of only 2.05. Thus, as a predictor of radiographic damage, the anti-CCP antibody will need to be assessed together with other predictors of poor radiographic outcome to have any clinical utility.

OP0015 THE DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF AUTOANTIBODIES IN PATIENTS WITH VERY EARLY ARTHRITIS
V Nell, K Machold, G Eberl, H Hiesberger, E Hoefler, J Smolen, G Steiner

and

OP0016 ANTI-CCP ANTIBODIES AND IGA-RHEUMATOID FACTOR PREDICT THE DEVELOPMENT OF RHEUMATOID ARTHRITIS
S Rantapaa Dahlqvist, B De Jong, E Berglin, G Hallmans, G Wadell, H Stenlund, U Sundin

While the above study (OP0013) assessed the value of anti-CCP as a predictor for radiographic progression in patients with early RA, these two studies evaluate diagnostic significance of anti-CCP in patients with early RA (OP0015) and the prevalence and predictive value of anti-CCP in the development of rheumatoid arthritis (OP0016).

OP0015:
Methods: 180 patients with very early arthritis (< 3 months) were included in this 6 month prospective study. Rheumatoid Factor (RF), anti-CCP, and hnRNP-A2/RA33 antigen (anti-A2/RA33) were measured.

Results: To date, RA was diagnosed in 100 patients. The table below is the results of the antibody measurements.

As in abstract OP0013, a correlation (p<0.05) was found between baseline anti-CCP and radiological outcome at the last observation.

OP0016:
Methods: 83 patients participating in the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden were found to have donated blood prior to the onset of RA. Four controls per sample, matched for age, sex, date of sampling and residential area, were selected randomly from the same cohorts. 21 patients had blood samples as early as 13.2 + 6.4 years prior to their RA symptoms. Anti-CCP and rheumatoid factor (IgM-RF, IgA-RF, and IgG-RF) were measured.

Results: Anti-CCP antibodies were found years prior to the onset of RA and increased in frequency until onset of disease. The following table shows the prevalence of these antibodies prior to RA onset.

The sensitivity for anti-CCP antibodies from samples > 1.5 years prior to symptom onset was 25% (15.1-37) and from samples < 1.5 years was 52% (33.8-68.9). Specificity for anti-CCP was 98%. This increase in sensitivity prior to symptom onset was also significant for all RF isotypes; IgM-RF 15% and 30%, IgG-RF 12% and 27%, and for IgA-RF 29% and 39%, respectively.

Using logistic regression models, anti-CCP had a predictive value of 31.4% (< 1.5 years) and 29.6% (> 1.5 years) for the development of RA. Additionally, anti-CCP titres increased until disease onset.

Conclusion: The data from the above abstracts suggest the following: anti-CCP as well as RF have diagnostic and prognostic value in early RA; anti-CCP and IgA-RF have specificity for RA and are predictive of its development; anti-CCP antibodies and all RF isotypes can be detected years prior to the onset of any symptoms.

Editorial Comment: Anti-CCP antibodies, similar to RF are very specific for RA and are modestly sensitive. It should be noted that the patient population all have arthritis and have been evaluated by rheumatologists. Thus the sensitivity and specificity values do not reflect screening of the general population or screening done by non-rheumatologists. It remains to be seen if anti-CCP antibodies will add diagnostic utility above that achieved with the RF test.

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