Jun 30, 2011
Anti-CCP Antibody Linked to More Severe Arthritis
By Nancy Walsh, Contributing Writer, MedPage Today
May 13, 2010
MedPage Today Action Points
Explain to interested patients that if a certain type of antibody is present in their blood they may develop more severe arthritis and are likely to need aggressive treatment.
Patients with inflammatory arthritis who have anti-cyclic citrullinated peptide (anti-CCP) antibodies have more severe disease and show less benefit from treatment than those who are antibody negative, British researchers found.
At baseline, antibody positive patients had higher disease activity scores (4.4 versus 3.73, P<0.001) regardless of whether they were also positive for rheumatoid factor, according to Tracey M. Farragher, PhD, of the University of Manchester, and colleagues.
At five years, disease activity scores among patients who had the anti-CCP antibodies remained higher (4.41 versus 3.76, P<0.001) and patients had greater functional disability, the researchers reported in the May issue of Arthritis Care & Research.
In recent years, increasing attention has been paid to a potential role for anti-CCP antibodies in the diagnosis and classification of inflammatory arthritis, with some studies suggesting that these antibodies are a more sensitive biomarker than rheumatoid factor, which is the marker used in the diagnostic criteria of the American College of Rheumatology.
But few studies have compared the utility of the two types of antibodies in association with clinical outcomes such as disease activity, functional disability, and response to treatment.
To examine these associations, Farragher and colleagues recruited 916 individuals from the Norfolk Arthritis Register, a primary care-based inception cohort of patients with recent-onset arthritis.
Anti-CCP antibodies were present in 29.3%, and rheumatoid factor in 27.8%.
When patients were classified at baseline according to the presence of either or both antibodies, differences in disease activity and severity were seen only for those who were anti-CCP positive.
Patients who had anti-CCP antibodies at baseline were more likely to be older and male.
Compared with antibody-negative patients, they also were characterized by the following:
C-reactive protein level, 12 mg/L versus 3 mg/L, P<0.001
Swollen joint count, 8 versus 6, P<0.001
Disease activity score in 28 joints (DAS28), 4.4 versus 3.73, P<0.001
Health Assessment Questionnaire (HAQ) score, 0.88 versus 0.625, P<0.001
Over five years, patients who were anti-CCP positive had a mean change on their HAQ scores of 0.20 points (95% CI 0.09 to 0.31), which reflected a worsening of functional disability.
Those who were negative for the antibodies had no worsening in HAQ score, with a mean change of 0.005 (95% CI −0.06 to 0.07).
At five years, patients with anti-CCP antibodies had worse scores on other disease outcomes:
Swollen joint count, 3 versus 0
Tender joint count, 2 versus 1
DAS28, 3.09 versus 2.22
Presence of erosions, 80.6% versus 29.4%
Differences also were seen in treatment during the five years of follow-up. Patients who were positive at baseline were more likely to be treated with disease-modifying antirheumatic drugs and steroids (85.4% versus 37.5%, P<0.001).
Patients who were positive for the antibodies benefited less from treatment, particularly early treatment, than did antibody-negative patients.
Compared with anti-CCP negative patients who were never treated, anti-CCP negative patients who were treated early had a significant improvement in functional disability at five years, with a mean adjusted difference in HAQ score of −0.31 (95% CI −0.53 to −0.09).
In contrast, there was no significant change in HAQ score in anti-CCP positive patients treated early (mean change −0.14, 95% CI −0.52 to 0.24) compared with those who were never treated.
Anti-CCP antibody negative patients also experienced significant additional benefit for each month of early treatment (−0.13, 95% CI −0.22 to −0.04), while anti-CCP positive patients did not (−0.05, 95% CI −0.18 to 0.07).
"In our analysis of patients with early [inflammatory polyarthritis], we found that at baseline and five years, all of the disease outcome measures were differentiated by anti-CCP antibody status rather than [rheumatoid factor] at baseline," Farragher and colleagues wrote.
A strength of the study was its use of a primary care-based cohort of patients with inflammatory polyarthritis, so there was limited selection bias.
In addition, the researchers used a statistical method that adjusted for time-varying confounders such as fluctuating disease activity.
However, there may have been residual confounding from unmeasured variables.
Other limitations included the fact that the study was conducted before the use of biological agents such as anti-TNF drugs and the inability to know whether seronegative patients converted over time.
The investigators concluded that anti-CCP positive patients require more aggressive treatment, and that future clinical trials of rheumatoid arthritis should stratify for anti-CCP antibody status.
"Our study provides further evidence for the reevaluation of the 1987 classification criteria for RA, and support for including anti-CCP antibody status as well as [rheumatoid factor] status," they wrote.