The performance of anti-cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: results from the Norfolk Arthritis Register

Abstract

Objective: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are a stronger predictor of the severity of rheumatoid arthritis than is rheumatoid factor (RF). Their role in predicting outcome in unselected patients with new-onset inflammatory polyarthritis (IP) has not been examined. The aims of this study were to examine the role of baseline RF and anti-CCP antibodies in determining the likelihood of patients having erosions at presentation or in predicting future radiologic damage, and to determine whether anti-CCP antibodies or RF is sufficiently robust to be clinically useful in guiding treatment decisions in early IP.

Methods: Patients were recruited from the Norfolk Arthritis Register. Logistic regression models were fitted to test the ability of anti-CCP antibodies and RF to predict erosions. Further models were investigated to examine the role of anti-CCP antibodies in patients stratified by RF status.

Results: The presence of anti-CCP antibodies at baseline was strongly associated with both prevalent erosions (odds ratio [OR] 2.53 [95% confidence interval (95% CI) 1.48-4.30]) and developing erosions at 5 years (OR 10.2 [95% CI 6.2-16.9]). These ORs were higher than those for RF (OR 1.63 [95% CI 0.94-2.82] and OR 3.4 [95% CI 2.2-5.2], respectively). The likelihood ratio (LR) for the prediction of prevalent erosions and erosions at 5 years was highest in the RF-subgroup (LR 2.2 and 5.8, respectively). However, 27% of anti-CCP-patients had developed erosions by 5 years.

Conclusion: Despite their strong association with the presence, development, and extent of erosions, anti-CCP antibodies alone are not a sufficiently accurate measure upon which to base clinical treatment decisions. Knowledge of anti-CCP antibody status is most informative in RF-negative patients.

Figure 1

Distribution of Larsen scores at baseline in all subjects (A) and in subjects with prevalent erosions (B), according to baseline antibody status in the cross-sectional cohort. Values are presented as box and whisker plots, where the boxes represent the interquartile range, the lines within the boxes represent the median Larsen score, the whiskers represent the range from the smallest to the largest score, and the circles represent outliers. No significant differences between the groups were noted. 1 represents subjects who were RF+ and anti-CCP+ (P = 0.07 versus subjects who were RF− and anti-CCP− in the total group and P = 0.70 versus subjects who were RF− and anti-CCP− in the group with erosions). 2 represents subjects who were RF− and anti-CCP+ (P = 0.06 versus subjects who were RF− and anti-CCP− in the total group and P = 0.49 versus subjects who were RF− and anti-CCP− in the group with erosions). 3 represents subjects who were RF+ and anti-CCP− (P = 0.90 versus subjects who were RF− and anti-CCP− in the total group and P = 0.34 versus subjects who were RF− and anti-CCP− in the group with erosions). 4 represents subjects who were RF− and anti-CCP− (referent).

Figure 2

Distribution of Larsen scores at 5 years in all subjects (A) and in subjects with erosions (B), according to baseline antibody status in the prospective cohort. Values are presented as box and whisker plots, where the boxes represent the interquartile range, the lines within the boxes represent the median Larsen score, the whiskers represent the range from the smallest to the largest score, and the circles represent outliers. 1 represents subjects who were RF+ and anti-CCP+ (P < 0.0001 versus subjects who were RF− and anti-CCP−, both in the total group and in the group with erosions). 2 represents subjects who were RF− and anti-CCP+ (P < versus subjects who were RF− and anti-CCP− in the total group and P = 0.0001 versus subjects who were RF− and anti-CCP− in the group with erosions). 3 represents subjects who were RF+ and anti-CCP− (P = 0.90 versus subjects who were RF− and anti-CCP− in the total group and P = 0.85 versus subjects who were RF− and anti-CCP− in the group with erosions). 4 represents subjects who were RF− and anti-CCP− (referent).