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

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.