Background: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. We prospectively investigated the effect of ACPA presence and levels on arthritis development in arthralgia patients.
Methods: Arthralgia patients positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox-regression hazard analyses were used to calculate hazard ratios (HR) for arthritis development.
Results: 147 arthralgia patients were included (52 ACPA positive, 50 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range [IQR] 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR 6.0; 95% confidence interval [95% CI] 1.8-20.1; P = 0.003), but not of IgM-RF (HR 1.4, 95% CI 0.6-3.1) nor the SE (HR 1.5, 95% CI 0.7-3.0) was associated with arthritis development. Within the group of ACPA positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR 3.0; 95% CI 1.3-6.9; P = 0.01 and high ACPA levels (HR 1.7; 95% CI 1.1-2.5; P = 0.008), but not the SE (HR 1.0; 95% C.I. 0.5-2.1; P = 1.0).
Conclusion: In arthralgia patients the presence of ACPA, (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.