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. 2005 Apr 20;64(12):1744–1749. doi: 10.1136/ard.2004.033571

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

J Ronnelid 1, M Wick 1, J Lampa 1, S Lindblad 1, B Nordmark 1, L Klareskog 1, R F van Vollenhoven 1
PMCID: PMC1755292  PMID: 15843452

Abstract

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.

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Figure 1.

Figure 1

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 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 the indicated time points. *p<0.05; **p<0.01; ***p<0.001.

Figure 2.

Figure 2

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 Changes in mean Larsen score (SEM) among anti-CP negative and anti-CP positive patients separately.

Figure 3.

Figure 3

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 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 comparisons were performed between baseline and the indicated time points (asterisks above the graph; all differences denoting decreased ratios over time) and between various time points and 5 years (asterisks below the graph, all differences denoting increased ratios over time). *p<0.05; ***p<0.001. The same highly significant drop in anti-CP levels was also found between baseline and 3 months and 1 year, respectively, when the whole group of 279 patients was investigated.

Figure 4.

Figure 4

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 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 the patient had the drug prescribed for at least 3 months but not for the whole year. "Entire period" indicates that the drug was prescribed at the baseline visit with continuous treatment at 3, 6, and 9 month visits. On the ordinate the ratio between the anti-CP levels at 1 year and baseline is depicted. A few patients who increased more than 100% during the study period have been omitted from the figure but are included in the statistical calculations. Horizontal bars indicate median ratios for the corresponding groups. Only anti-CP positive patients have been included.

Selected References

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