May 23, 2011 — Anti-citrullinated protein antibody (ACPA) is a better tool for classifying rheumatoid arthritis (RA) than rheumatoid factor (RF) levels are and should replace RF levels when the 2010 American College of Rheumatology/European Union League Against Rheumatism (ACR/EULAR) criteria for RA diagnosis are revised, a panel of European experts writes in the May issue of Arthritis & Rheumatism.
M.P.M. van der Linden, MD, and colleagues analyzed the positive and negative predictive values of different levels of RF and ACPA in 972 patients with undifferentiated arthritis studied for RA development and for arthritis persistence.
"Our findings indicate that determination of RF level is subject to large variation; high RF level has limited additive prognostic value compared to ACP positivity. Thus, omitting RF level and using RF presence, ACPA presence, and ACPA level may improve the 2010 criteria for RA," the authors write.
The investigators examined the value of different RF titers for predicting RA classification in patients for whom ACPA status is known. Given the lack of standardization of RF measurement, they used both the RF cutoff from the 2010 RA classification criteria (low-positive RF is any level higher than the upper limit of normal [ULN] but ≤3 times the ULN; high-positive RF is > 3 times ULN) and the definition of high-positive RF as any level greater than 50 units/mL (RF50).
The researchers also compared ACPA and RF for predicting rate of joint destruction and achievement of freedom from disease-modifying antirheumatic drug (DMARD) therapy in 686 patients with RA during 7 years of follow-up.
The researchers report that the odds of developing RA might increase with or without a high RF level.
The risk for not achieving DMARD-free remission was higher in patients with ACPA positivity (hazard ratio, 11.3), RF level at 3 or more times the reference value (hazard ratio, 5.7), or RF50 (hazard ratio, 3.1).
The researchers also examined variations in RF levels in measurements of the same RF-positive sera by different methods. "Despite the existence of international units for RF, RF level measurement is not adequately standardized between different methods," the authors note. They found that even assessing RF level in relation to a standard reference serum did not increase reproducibility of the results between laboratories or between methods.
The analysis showed that ACPA testing in addition to measuring RF levels added little to predictive accuracy for RA development.
"The results of the present study revealed that the overall prognostic ability of ACPA positivity outweighs that of high RF level in patients with [undifferentiated arthritis]. For this reason, we suggest that a future modification of the classification criteria for RA should include ACPA determination but not RF level," the authors conclude.
An accompanying editorial by Katherine P. Liao, MD, MPH, Michael E. Weinblatt, MD, and Daniel H. Solomon, MD, MPH, all of Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, sounds a more cautious note.
Dr. Liao and colleagues write, "[T]he study findings are unlikely to settle the debate regarding whether the presence of RF or RF levels should remain part of the classification criteria," particularly because the authors analyzed RF levels and ACPA levels "in isolation from other aspects of the 2010 RA classification criteria."
The editorialists also point to the dangers of constant tinkering with criteria, warning that it "would undermine the overall goal of this exercise, which is to harmonize studies' classification criteria, facilitating comparison." They particularly warn against changing the 2010 criteria "before investigators and clinicians have had a chance to see how they perform in studies and in practice."
Arthritis Rheum. 2011;63:1170-1172, 1190-1199 Abstract
http://www.medscape.com/viewarticle/743199