The risk of individual autoantibodies, autoantibody combinations and levels for arthritis development in clinically suspect arthralgia.

Objectives: Autoantibody testing is helpful for predicting the risk of progression to clinical arthritis in subjects at risk. Previous longitudinal studies have mainly selected autoantibody-positive arthralgia patients, and consequently the predictive values of autoantibodies were evaluated relative to one another. This study assessed the risks for arthritis development of ACPA, RF and/or anti-carbamylated protein antibodies (anti-CarP) in arthralgia patients considered at risk for RA by rheumatologists, based on clinical characteristics (clinically suspect arthralgia, CSA).

Methods: The baseline ACPA, RF and anti-CarP autoantibody status of 241 patients, consecutively included in the CSA cohort, was studied for risk of developing clinical arthritis during a median follow-up of 103 (interquartile range: 81-114) weeks.

Results: Univariable associations for arthritis development were observed for ACPA, RF and anti-CarP antibodies; hazard ratios (HRs) (95% CI) were 8.5 (4.7-15.5), 5.1 (2.8-9.3) and 3.9 (1.9-7.7), respectively. In multivariable analysis, only ACPA was independently associated (HR = 5.1; 2.0-13.2). Relative to autoantibody-negative CSA patients, ACPA-negative/RF-positive patients had HRs of 2.6 (1.04-6.6), ACPA-positive/RF-negative patients 8.0 (2.4-27.4) and ACPA-positive/RF-positive patients 10.5 (5.4-20.6). Positive predictive values for development of clinical arthritis within 2 years were: 38% for ACPA-negative/RF-positive, 50% for ACPA-positive/RF-negative and 67% for ACPA-positive/RF-positive patients. Higher ACPA levels were not significantly associated with increased progression to clinical arthritis, in contrast to higher RF levels. Autoantibody levels were stable during follow-up.

Conclusion: ACPA conferred the highest risk for arthritis development and had an additive value to RF. However, >30% of ACPA-positive/RF-positive CSA patients did not develop arthritis during the 2-year follow-up. Thus, CSA and information on autoantibodies is insufficient for accurately identifying imminent autoantibody-positive RA.