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

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

Sune F Nielsen  1 , Stig E Bojesen, Peter Schnohr, Børge G Nordestgaard
Affiliations

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

Sune F Nielsen et al. BMJ. .

Abstract

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Box and whisker plots of distribution of plasma rheumatoid factor levels in 10 year age groups in 9712 participants without rheumatoid arthritis in the Copenhagen City Heart Study
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Fig 2 Risk of autoimmune rheumatic diseases as a function of doubling of rheumatoid factor level in 9712 participants in the Copenhagen City Heart Study followed for up to 28 years. All hazard ratios were multivariable adjusted (see text for details)
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Fig 3 Kaplan-Meier cumulative incidence of rheumatoid arthritis for four categories of baseline level of rheumatoid factor as a function of age in 9712 participants in the Copenhagen City Heart Study followed for up to 28 years
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Fig 4 Risk of rheumatoid arthritis as a function of rheumatoid factor level in 9712 participants in the Copenhagen City Heart Study by length of follow-up (full 28 years or first 10 years) and number of hospitalisations for rheumatoid arthritis. All hazard ratios were multivariable adjusted (see text for details)
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Fig 5 Absolute 10 year risk of rheumatoid arthritis in 9712 participants in the Copenhagen City Heart Study as a function of rheumatoid factor level, age, sex, and smoking status
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