Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis

Ann Intern Med. 2007 Jun 5;146(11):797-808. doi: 10.7326/0003-4819-146-11-200706050-00008.


Background: Rheumatoid factor (RF) and autoantibodies against cyclic citrullinated peptide (CCP) are markers that might help physicians diagnose rheumatoid arthritis.

Purpose: To determine whether anti-CCP antibody more accurately identifies patients with rheumatoid arthritis and better predicts radiographic progression than does RF.

Data sources: MEDLINE through September 2006 and reference lists of retrieved studies and review articles.

Study selection: Studies in any language that enrolled at least 10 participants and that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis of known or suspected rheumatoid arthritis.

Data extraction: Two authors independently evaluated studies for inclusion, rated methodological quality, and abstracted relevant data.

Data synthesis: The DerSimonian-Laird random-effects method was used to summarize sensitivities, specificities, and positive and negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of RF. The pooled sensitivity, specificity, and positive and negative likelihood ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%), 12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF, the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to 5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and IgA RF seemed to be similar. Results from studies of patients with early rheumatoid arthritis were similar to those from all studies. Three of 4 studies found that risk for radiographic progression was greater with anti-CCP antibody positivity than with IgM RF positivity.

Limitations: Many studies had methodological limitations. Studies of RF were heterogeneous and had wide ranges of sensitivity and specificity.

Conclusions: Anti-CCP antibodies are more specific than RF for diagnosing rheumatoid arthritis and may better predict erosivedisease.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthritis, Rheumatoid / diagnosis*
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Likelihood Functions
  • Peptides, Cyclic / immunology*
  • Prognosis
  • Rheumatoid Factor / blood*
  • Sensitivity and Specificity


  • Autoantibodies
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor