The utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies is well-established as a diagnostic and prognostic tool in rheumatoid arthritis and as a predictor of RA risk in established undifferentiated arthritis (UA). The 2010 RA classification criteria include anti-CCP as a key item. A new two-year study from Italy finds that the presence of anti-CCP positivity has value in recent-onset UA, predicting the development of future RA -- and even predicting the interval between first symptoms and RA onset.
Researchers at clinics in the FIRMA group, an Italian association of specialists in autoimmune rheumatic diseases) studied 192 consecutive patients with UA of <12 weeks onset. They found that anti-CCP titers -- both high and low -- predict a significant risk of RA in such patients, comparable to other markers such as rheumatoid factor (RF) and C-reactive protein (CRP).
The researchers note that recent-onset UA accounts for 30-50% of patients presenting to rheumatologists and that the presence of anti-CCP antibodies aids early diagnosis, allowing introduction of methotrexate therapy to delay progression to RA and joint damage.
A majority of the patients in the multi-center study were middle-aged women (147 females and 45 males, mean age 52) almost 70% presenting with polyarthritis, mostly in the hands.
At baseline, around 41% of patients tested RF-positive and/or anti-CCP positive, with a majority of the latter group (73.6%) progressing to RA by the end of the study. While high RF levels at baseline predicted RA progression, low titers did not -- while anti-CCP positivity at any level was predictive of progression.
Higher CRP levels but not erythrocyte sedimentation rates (ESR) at baseline associate with a greater possibility of developing RA at two years. In a multivariate analysis (adjusted for CRP, RF and anti-CCP), only arthritis of the hands in patients with high and low baseline anti-CCP predict progression to RA meeting classification criteria.
One of the most interesting findings is that the rapidity of progression appears to correlate directly with the anti-CCP level, the first report of such a correlation. However, anti-CCP concentration does not appear to correlate with disease outcomes or radiographic progression. Therapy with anti-inflammatory drugs or DMARDs did not alter anti-CCP levels.
The researchers conclude that “initial anti-CCP levels appear to be of great importance in predicting interval time to disease onset, since a delay in RA diagnosis could occur in subjects with low antibody levels at symptom onset” -- suggesting the need for closer follow-up of early UA patients and further studies of genetic influence and therapeutic interventions in high-risk subgroups.