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.