Anticitrullinated Protein Antibody, But Not Its Titer, Is a Predictor of Radiographic Progression and Disease Activity in Rheumatoid Arthritis

Abstract

To study the contribution of anticitrullinated protein antibody (ACPA), and especially of its titer, to radiographic progression and disease activity in rheumatoid arthritis (RA). Patients with RA (n = 396) who attended a Japanese clinic within 2 years after disease onset were divided into the following groups according to second-generation (ACPA-2) ACPA titer on their first visit: negative (0-4.4 U/ml; n = 115), low-positive (4.5-121 U/ml; n = 141), and high-positive (> 121 U/ml; n = 140). The ACPA-2-positive groups were further subdivided into lowest (4.5-32 U/ml), low (33-121 U/ml), high (122-277 U/ml), and highest (> 278 U/ml) quartiles. All patients were treated with disease-modifying antirheumatic drugs (DMARD) including methotrexate, but not biologics. Subsequent radiographic progression and disease activity for 2 years were prospectively evaluated using the van der Heijde-modified Sharp score (SHS) and 28-joint Disease Activity Score (DAS28). After treatment with DMARD, the disease activity (including number of swollen joints, number of tender joints, duration of morning stiffness, DAS28-erythrocyte sedimentation rate, and DAS28-C-reactive protein) was significantly decreased in all patient groups. Disease activity and radiographic progression as revealed by the change in SHS remained relatively higher in the ACPA-2 low- and high-positive groups as compared with the ACPA-2-negative group. The relationship between the titer of ACPA-2 at baseline and subsequent radiographic progression was not exactly linear, and the extent of disease activity or radiographic progression was similar between ACPA-2 low- and high-positive groups and also between ACPA-2 lowest- and highest-positive quartile groups. The results were demonstrable in cumulative SHS probability plots, and also repeatable in seronegative patients, which indicated that the titer of ACPA-2 is not a predictor of disease activity or radiographic progression in RA, and ACPA-2-negative patients, especially those with < 3 U/ml, showed minimal radiographic progression. Presence of ACPA-2, but not its titer, at baseline is a predictor of radiographic progression or disease activity, where radiographic progression is minimal in ACPA-2-negative patients.