Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study

Arthritis Rheum. 2004 Mar;50(3):709-15. doi: 10.1002/art.20044.


Objective: Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an inception cohort of patients with recent-onset arthritis, we undertook this study to assess the predictive value of RA-specific autoantibodies to cyclic citrullinated peptides (CCPs) in patients with undifferentiated arthritis (UA).

Methods: Anti-CCP2 antibody tests were performed at baseline in 936 consecutive, newly referred patients with recent-onset arthritis. Patients who could not be properly classified 2 weeks after inclusion were categorized as having UA. Patients with UA were followed up for 3 years and evaluated for progression of their disease to RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria.

Results: Three hundred eighteen of 936 patients with recent-onset arthritis were classified as having UA and were available for analysis. After 3 years of followup, 127 of 318 UA patients (40%) had been classified as having RA. RA had developed in 63 of 249 patients (25%) with a negative anti-CCP test and in 64 of 69 patients (93%) with a positive anti-CCP test (odds ratio 37.8 [95% confidence interval 13.8-111.9]). Multivariate analysis of the presence of anti-CCP antibodies and parameters from the ACR criteria identified polyarthritis, symmetric arthritis, erosions on radiographs, and anti-CCP antibodies as significant predictors of RA.

Conclusion: Testing for anti-CCP antibodies in UA allows accurate prediction of a substantial number of patients who will fulfill the ACR criteria for RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis / complications*
  • Arthritis / diagnostic imaging
  • Arthritis / immunology*
  • Arthritis, Rheumatoid / etiology*
  • Autoantibodies / analysis*
  • Citrulline / metabolism*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Peptides, Cyclic / metabolism*
  • Prognosis
  • Prospective Studies
  • Radiography
  • Risk Factors


  • Autoantibodies
  • Peptides, Cyclic
  • Citrulline