Rheumatoid factor, not antibodies against citrullinated proteins, is associated with baseline disease activity in rheumatoid arthritis clinical trials

Arthritis Res Ther. 2015 Aug 26;17(1):229. doi: 10.1186/s13075-015-0736-9.


Introduction: Although the prognostic value of rheumatoid factor (RF) and autoantibodies against citrullinated proteins (ACPAs) in patients with rheumatoid arthritis (RA) is well established, their association with RA disease activity remains unclear. Here, we investigate this association in a large study using data from clinical trials.

Methods: We used baseline data from four recent randomized controlled clinical trials of RA. We investigated individual and composite measures of disease activity. The relationship of RF and ACPAs with these measures was investigated by using stratified analysis (comparing four groups of patients according to the presence or absence of RF and ACPAs) and matched analysis (disease activity levels compared between patients negative and patients highly positive for one autoantibody who were matched for levels of the other autoantibody as well as for age, gender, and duration of RA).

Results: A total of 2118 patients were analysed in the different cohorts. In the stratified analysis, RF(+) patients, regardless of ACPA status, had the highest levels of disease activity, whereas ACPA(+) patients had disease activity that was similar to or lower than that of ACPA(-) patients, both in the presence and in the absence of RF. When matched for ACPA levels, patients with highly positive RF had significantly higher disease activity for all composite indices compared with patients who were RF(-) (P = 0.0067), whereas ACPA-highly-positive and ACPA-negative patients matched for RF levels had similar disease activity, again even with the tendency toward lower disease activity for ACPA(+) patients (P = 0.054).

Conclusion: The data presented suggest that the presence of RF has a clear association with higher levels of disease activity but that the presence of ACPAs has not and even appears to be associated with lower disease activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Autoantibodies / immunology*
  • Citrulline / immunology*
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Peptides, Cyclic / immunology*
  • Randomized Controlled Trials as Topic
  • Rheumatoid Factor / immunology*
  • Rituximab / therapeutic use
  • Severity of Illness Index


  • Antirheumatic Agents
  • Autoantibodies
  • Peptides, Cyclic
  • Citrulline
  • Rituximab
  • Rheumatoid Factor
  • Methotrexate