Autoantibody Tests to Predict Rapid Radiographic RA Progression

Measurement of anti-citrullinated peptide antibodies to predict erosive rheumatoid arthritis was examined in a study of adult patients with early disease.

Autoantibody tests are commonly used to aid in the diagnosis of rheumatoid arthritis (RA), but a new study suggests that these tests might also be helpful in predicting which patients with early RA are more likely to show rapid radiographic progression (RRP) of disease at 1 year.1

The study compared the predictive performance of 3 different anti-citrullinated peptide antibody (ACPA) diagnostic tests: a second-generation anti-citrullinated peptide (anti-CCP2) assay; an anti-mutated citrullinated vimentin (anti-MCV) assay; and an anti-citrullinated fibrinogen antibody (AhFibA) assay.

“These 3 tests have shown similar reliability in diagnosing RA early in the disease process, and several studies have suggested that they might also be predictive of structural outcomes, but the results have thus far been inconsistent,” said study lead author Yannick Degboé, MD, from the Rheumatology Center at Purpan University Hospital in Toulouse, France, in an email interview with Rheumatology Advisor. “We wanted to see if these tests could be used to help clinicians identify patients who will develop severe destructive disease so that they have the chance to start appropriate interventions before there is irreversible damage,” he noted.

The study conducted by Dr Degboé and colleagues included 566 patients (mean age, 50.5 years) from the ESPOIR cohort—a longitudinal, prospective, multicenter, observational study of adult patients with early RA treated in France—for whom complete biological and radiographic data were available. The primary end point was performance of the 3 ACPA tests in predicting RRP of RA at 1 year, which was determined by comparing areas under the receiver operating characteristic (ROC) curves. Secondary end points included risk of progression based on ACPA positivity and high (>3N) and low (1-3N) antibody titers.

Of the study patients, 145 had RRP at 1 year, with ROC analysis showing all 3 tests to have similar predictability. The areas under the curve for anti-CCP2, anti-MCV, and AhFibA assays were 0.601 (95% confidence interval [CI], 0.550-0.651), 0.607 (95% CI, 0.555-0.659), and 0.599 (95% CI, 0.547-0.651), respectively. A high titer on any ACPA test at baseline was associated with RRP at 1 year.

Additionally, low titers on the anti-CCP2 (P=.0226) and AhFibA (P=.0332) assays at baseline were significantly associated with RRP at 1 year, with approximately 33% of such patients having RRP at 1 year. In contrast, low anti-MCV titers were not significantly associated with RRP, with only 13.7% of these patients having RRP at 1 year.

Dr Degboé and colleagues performed several multivariate analyses to confirm the independence of the ACPA and 1-year RRP associations that they observed. They found that 1-year RRP was associated with anti-CCP2 positivity (P<.0001), AhFibA positivity (P<.0001), and high anti-MCV titers (P<.0001).

“Because, unlike the other ACPA diagnostic tests, only high anti-MCV titers were predictive of RRP at 1 year, this test might be more discriminant in predicting 1-year RRP risk,” said Dr Degboé. “Therefore, clinicians should pay attention to titer, and not just positivity, when using anti-MCV test results to determine prognosis.”

Summary and Clinical Applicability

High ACPA titers can help diagnose RA and identify patients who are likely to have rapid disease progression and a worse prognosis.

Both anti-CCP2 and anti-MCV antibodies can help identify patients who are likely to have disease progression. However, in the case of anti-MCV antibodies, only high titers were predictive of rapid progression. Therefore, Dr Degboé recommends that clinicians consider antibody titers when evaluating results of antibody tests.

Although anti-CCP2 testing remains the gold standard in RA testing, assays of other citrullinated peptides may provide additional insight and could be especially useful for serodiscordant patients. Dr Degboé noted that his study did not include such patients because the small number of patients in subgroups prohibited meaningful subclass analysis; however, this remains an important area for future investigation.


Degboé Y, Constantin A, Nigon D, et al. Predictive value of autoantibodies from anti-CCP2, anti-MCV and anti-human citrullinated fibrinogen tests, in early rheumatoid arthritis patients with rapid radiographic progression at 1 year: results from the ESPOIR cohort. RMD Open. 2015;1(1):e000180.