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Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 2005 December; 64(12): 1744–1749.
Published online 2005 April 20. doi:  10.1136/ard.2004.033571
PMCID: PMC1755292

Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression


Objective: To study serum levels of citrullinated protein/peptide antibodies (anti-CP) during up to 5 years' follow up of patients with early rheumatoid arthritis (RA), and to relate serum levels to disease course and to treatments in clinical practice.

Methods: 279 patients with early RA were followed up with clinical investigations, radiographs, and measurement of anti-CP at baseline and after 3 months, 1, 2, 3, and 5 years.

Results: 160/279 (57.3%) patients were anti-CP positive at the first visit (mean 5 months after first symptoms). During follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti-CP levels fell significantly during the first year, and this drop correlated with the extent of sulfasalazine treatment but not with other drugs or clinical indices. Anti-CP positive and negative patients had similar disease activities at baseline, but during follow up the anti-CP positive patients had worse clinical disease and greater radiological progression, despite at least equally intensive antirheumatic treatment.

Conclusions: Anti-CP are stable during the first 5 years of RA, suggesting that events before rather than after onset of clinical manifestations of disease determine this phenotype. The presence of anti-CP at diagnosis predicts a less favourable disease course and greater radiological progression despite antirheumatic treatment, but subsequent changes in antibody levels do not reflect changes in disease activity. Taken together, these observations suggest that anti-CP positive RA is a distinct clinical and pathophysiological entity.

Figure 1
 Changes in mean clinical indices detailed in table 1 for anti-CP positive (anti-CP+) and anti-CP negative (anti-CP–) patients treated separately. Statistical comparisons were performed between anti-CP positive and negative patients at ...
Figure 2
 Changes in mean Larsen score (SEM) among anti-CP negative and anti-CP positive patients separately.
Figure 3
 Percentage change in median anti-CP antibody levels among the anti-CP positive patients of the subgroup of 77 patients with RA for whom serum samples were obtained at baseline and after 3 months, 1, 2, 3, and 5 years, respectively. Paired statistical ...
Figure 4
 Changes in anti-CP levels during the first year as a function of treatment with (A) sulfasalazine and (B) methotrexate. "Never" indicates that the patient had not had the drug prescribed at any time point during the period, and "partly" that ...

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