Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study

BMJ. 2012 Sep 6;345:e5244. doi: 10.1136/bmj.e5244.


Objective: To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.

Design: A prospective cohort study, the Copenhagen City Heart Study. Blood was drawn in 1981-83, and participants were followed until 10 August 2010.

Setting: Copenhagen general population.

Participants: 9712 white Danish individuals from the general population aged 20-100 years without rheumatoid arthritis at study entry.

Main outcome measures: Rheumatoid arthritis according to baseline plasma IgM rheumatoid factor level categories of 25-50, 50.1-100, and >100, versus <25 IU/mL.

Results: Rheumatoid factor levels were similar from age 20 to 100 years. During 187,659 person years, 183 individuals developed rheumatoid arthritis. In healthy individuals, a doubling in levels of rheumatoid factor was associated with a 3.3-fold (95% confidence interval 2.7 to 4.0) increased risk of developing rheumatoid arthritis, with a similar trend for most other autoimmune rheumatic diseases. The cumulative incidence of rheumatoid arthritis increased with increasing rheumatoid factor category (P(trend)<0.0001). Multivariable adjusted hazard ratios for rheumatoid arthritis were 3.6 (95% confidence interval 1.7 to 7.3) for rheumatoid factor levels of 25-50 IU/mL, 6.0 (3.4 to 10) for 50.1-100 IU/mL, and 26 (15 to 46) for >100 IU/mL, compared with <25 IU/mL (P(trend)<0.0001). The highest absolute 10 year risk of rheumatoid arthritis of 32% was observed in 50-69 years old women who smoked with rheumatoid factor levels >100 IU/mL.

Conclusion: Individuals in the general population with elevated rheumatoid factor have up to 26-fold greater long term risk of rheumatoid arthritis, and up to 32% 10 year absolute risk of rheumatoid arthritis. These novel findings may lead to revision of guidelines for early referral to a rheumatologist and early arthritis clinics based on rheumatoid factor testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / etiology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Rheumatoid Factor / blood*
  • Risk Factors
  • Sex Factors
  • Smoking / adverse effects
  • Young Adult


  • Rheumatoid Factor