More Severe Erosive Disease Observed in ACPA-Positive vs ACPA-Negative Rheumatoid Arthritis

ACPA-positive rheumatoid arthritis was associated with more severe erosive disease compared with ACPA-negative rheumatoid arthritis.

Per study data published in Rheumatology International, anti-citrullinated protein antibody (ACPA)-positive (ACPA+) rheumatoid arthritis (RA) was associated with more severe erosive disease compared with ACPA-negative (ACPA-) RA.

To assess the prevalence, localization, and severity of bone erosions on radiography and ultrasonography (US) studies, investigators performed a retrospective study of patients with RA who received care between 2005 and 2016 at the Nancy University Hospital Department of Rheumatology in Nancy, France. Patients who underwent US of the hands and feet by 1 of 2 senior participating physicians were consecutively selected for inclusion. Disease assessment data were extracted from participants’ medical records, including ACPA status and information from clinical, biological, radiographic, and US evaluations.

In radiographic analyses, 2 independent readers determined the modified Sharp/van der Heijde score for erosions (SHSe) with subscores for the hands and feet. In US analyses, erosions were scored semiquantitatively on a 4-grade scale, with grade 0 representing no erosion and grade 3 representing a single erosion ≥3 mm or multiple erosions. The total US score for erosions was the sum of erosion grades for all eroded joints. Patients were classified as having erosive RA per the 2013 European League Against Rheumatism definition using both radiographic and US data. Multivariate logistic regression was performed to identify associations between ACPA status and erosive RA.

Related Articles

A total of 108 patients with RA were included in analyses, among whom 78 (72.2%) had ACPA+ RA and 30 (27.8%) had ACPA- RA. Mean (standard deviation [SD]) age in the total cohort was 54.5 (13.5) years, and 78 (72.2%) were women. Patients with ACPA+ RA were more often men (33.3% vs 13.3%; P =.04) and more often positive for rheumatoid factor (71.8% vs 23.3%; P <.001) than were patients with ACPA- RA. In radiographic analyses, a greater proportion of the ACPA+ group was diagnosed with erosive RA compared with the ACPA- group (42.3% vs 13.3%). The mean (SD) total SHSe values were 15.3 (22.1) and 4.1 (8.3) in the ACPA+ and ACPA- groups, respectively (P <.001). Compared with the ACPA- group, the ACPA+ group had higher mean SHSe values for all studied joints.

Bilateral erosion of the fifth metatarsophalangeal (MTP5) joint on radiographs was observed exclusively in the ACPA+ group (P <.01). In US analyses, 78.2% of the ACPA+ group and 46.7% of the ACPA- group met the criteria for erosive RA, respectively. The mean (SD) total US scores for erosions were 12.2 (11.7) and 2.8 (4.4) in the ACPA+ and ACPA- groups, respectively (P <.001). The MTP5 joints were the most frequently eroded joints in both groups, though the ACPA+ group displayed more severe erosions. Nearly all (97.8%) patients with bilateral MTP5 joint erosion on US were ACPA+ (P <.001).

In multivariate analyses, ACPA positivity significantly increased the risk for erosive disease on radiography (odds ratio [OR], 4.4; 95% CI, 1.2-16.4) and US (OR, 3.7; 95% CI, 1.4-9.9). Erosive RA was also predicted by longer disease duration, higher erythrocyte sedimentation rate, and use of biologic disease-modifying anti-rheumatic drugs.

These data suggest that ACPA+ RA is a distinct entity from ACPA- RA and may predict erosive disease. As a retrospective study with limited cohort size, results must be extrapolated with care because OR sizes may have been inflated. Even so, these results strongly support ACPA as a predictor for more severe erosive disease in RA.


Grosse J, Allado E, Roux C, et al. ACPA‑positive versus ACPA‑negative rheumatoid arthritis: two distinct erosive disease entities on radiography and ultrasonography [published online December 13, 2019]. Rheumatol Int. doi: 10.1007/s00296-019-04492-5