Background/Purpose: The association between inflammatory markers such as CRP or ESR and joint damage has been widely established in RA. Autoantibodies such as RF and anti-cyclic citrullinated peptide (anti-CCP) are also associated with severe joint damage. However, there are limited data on the association between markers of inflammation and autoantibodies. The objective of this analysis was to evaluate the association between CRP and anti-CCP using clinical practice data sets.

Methods: Two data sets were used: a single academic center, prospective, observational cohort registry of patients (pts) with RA, and the Optum Clinformatics Data Mart (Optum), which includes the Optum Medicare data. The registry was established in 2003 and primarily comprises pts with established RA. In Optum, pts with two ICD-9 codes for RA (714.0) and a prescription for a DMARD between Jan 2007 and Dec 2014 were identified. For inclusion in the current study, pts were required to have anti-CCP and CRP baseline values. The high normal concentration for anti-CCP was 19 U/ml in both data sets, and for CRP it was 5 mg/L in the registry and 4.9 mg/L in Optum. Pts meeting inclusion criteria were placed into CRP groups (grps) by quartiles and anti-CCP positivity was evaluated in each grp. Additional sensitivity analyses were conducted by grouping pts into two CRP grps, i.e., CRP ≥5 vs <5 mg/L. Multivariate logistic and linear regression for anti-CCP positivity were evaluated with CRP as an independent variable and controlling for baseline covariates. In the registry analysis, we adjusted for age, sex, race, BMI, Charlson co-morbidity index, RA duration, DAS28 (CRP) and treatment with biologic DMARDs. In Optum, we adjusted for age, sex, region, incident RA, co-morbidities, use of steroids, use of NSAIDs, use of salicylates and initiating a DMARD within 90 days after the index date.

Results: A total of 1309 pts from the registry and 3798 from Optum were included in the analysis. Pts in the high (vs low) CRP grps were older (mean [SD] 60.1 [13.2] vs 51.4 [14.0] yrs in the registry; 60.0 [15.7] vs 54.4 [14.9] yrs in Optum), had more males (23 vs 13% in the registry; 30 vs 21% in Optum) and a greater proportion of pts was anti-CCP positive (Figure). Based on multivariate logistic models, pts in CRP grp 3 vs grp 1 (odds ratio [95% CI] 2.08 [1.43, 3.03], p<0.001) and grp 4 vs grp 1 (1.87 [1.23, 2.84], p=0.003) had significantly higher odds of being anti-CCP positive in the registry. Similar findings were observed in Optum: grp 2 vs grp 1 (1.37 [1.15, 1.63], p<0.001); grp 3 vs grp 1 (1.68 [1.42, 2.00], p<0.001); and grp 4 vs grp 1 (2.09 [1.76, 2.48], p<0.001). The findings from the linear regression model and sensitivity analysis were consistent with those of the logistic regression model.

Conclusion: Analyses based on two independent data sources indicate that there is an association between CRP and anti-CCP levels in pts with RA. Pts with a high CRP level are more likely to be anti-CCP positive, with a higher anti-CCP level.