Abstract

The objective of this study was to evaluate the potential of serially determined anti-cyclic citrullinated peptide (CCP) antibodies for predicting structural joint damage in patients with early rheumatoid arthritis (RA), compared to a single baseline determination. Ninety-nine RA patients with disease durations of less than one year and no history of disease-modifying antirheumatic drug therapy were followed prospectively for at least five years. Anti-CCP2 concentrations were measured using a second-generation ELISA. Sharp scores as modified by van der Heijde were determined on hand and foot radiographs. Anti-CCP2 antibodies were detected in 55.5% of patients at baseline and 63.6% at any time during the first three years. Presence of anti-CCP2 at any time during the first three years was associated with radiographic damage at baseline (odds ratio (OR), 3.66; 95% confidence interval (95% CI) 0.99–13.54) and with five year progression of the total Sharp score (OR, 3.17; 95% CI, 1.3–7.7), erosion score (OR, 5.3; 95% CI, 1.4–19.2) and joint space narrowing score (OR, 2.8; 95% CI, 1.15–6.8). The presence of anti-CCP2 or IgM RF at baseline did not predict these outcomes. Patients with negative anti-CCP2 tests throughout follow-up had less radiographic progression than patients with increasing anti-CCP2 concentrations; they did not differ from patients with decreasing anti-CCP2 antibody levels. HLADRB1* typing showed that progression of the mean modified Sharp score was not correlated with the presence of the shared epitope alleles. In conclusion, serially determined anti-CCP2 antibodies during the first three years of follow-up performs better than baseline determination for predicting radiographic progression in patients with early RA.

Highlights

  • Autoantibodies to citrullinated cyclic peptides (CCPs) were recently described as useful diagnostic markers for rheumatoid arthritis (RA) [1]

  • We investigated whether the predictive value of anti-CCP2 for radiographic joint damage in RA could be improved by repeating the assays over time

  • We evaluated the effectiveness of anti-CCP2 and IgM RFs at baseline and over time for predicting radiographic progression after five years

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Summary

Introduction

Autoantibodies to citrullinated cyclic peptides (CCPs) were recently described as useful diagnostic markers for rheumatoid arthritis (RA) [1]. Studies that used the first-generation ELISA (CCP1) suggested that the presence of anti-CCPs might predict erosive disease in populations with early RA [27]. Similar results were obtained recently with the second-generation ELISA (CCP2) [8,9,10]. Not all patients with anti-CCPs go on to experience erosive disease. Anti-CCP2 is associated with erosions and radiographic progression, but most of the odds ratios (ORs) reported to date are only modestly elevated, in the 2.5 to 3.5 range. Models combining several parameters have been built in an attempt to identify patients at high risk for severe disease progression.

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