Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis

Abstract

Objective: To study the prognostic value of antibodies to cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF), alone and in combination, in patients with very early synovitis.

Methods: A cross-sectional study was performed in patients with established inflammatory and noninflammatory disease to validate the assay in our unit and confirm previously reported sensitivities and specificities of anti-CCP antibodies. Subsequently, patients with synovitis of 3 months' duration were followed for 72 weeks and the ability of anti-CCP antibodies and RF to predict the development of rheumatoid arthritis (RA) and persistent inflammatory arthritis was assessed.

Results: One hundred twenty-four patients were assessed in the initial cross-sectional study. Anti-CCP antibodies and RF were detected by ELISA in only 4% of patients with non-RA inflammatory disease and in no patient with noninflammatory disease. Ninety-six patients with very early synovitis were assessed longitudinally. In these patients with early arthritis, the combination of anti-CCP antibodies and RF had a specificity, positive predictive value (PPV), sensitivity, and negative predictive value (NPV) for a diagnosis of RA of 100%, 100%, 58%, and 88%, respectively. The specificity, PPV, sensitivity, and NPV of this antibody combination for the development of persistent disease-fulfilling classification criteria for RA were 97%, 86%, 63%, and 91%, respectively.

Conclusion: In patients with synovitis of 3 months' duration, a combination of anti-CCP antibodies and RF has a high specificity and PPV for the development of persistent RA. This autoantibody combination can be used to identify patients with disease destined to develop RA who may be appropriate for very early intervention.

Figure 1

Anti-CCP antibody titers (IU/ml) in patients with established rheumatological and non-rheumatological diagnoses in the cross-sectional study and in patients with very early inflammatory arthritis. WG: Wegener’s granulomatosis, SLE: systemic lupus erythematosus, AS: ankylosing spondylitis, IBD: inflammatory bowel disease, OA: osteoarthritis, RA: rheumatoid arthritis.

Figure 2

Outcomes of 97 patients with very early inflammatory arthritis. RA: rheumatoid arthritis, PsA: psoriatic arthritis, ReA: reactive arthritis; ARA: American Rheumatism Association, FU: followup..