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

INTRODUCTION: Autoantibody testing is helpful to predict 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 each other. This study assessed risks for arthritis development of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (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: 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 (IQR 81-114) weeks. RESULTS: Univariable associations for arthritis development were observed for ACPA, RF and anti-CarP antibodies; Hazard Ratios (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 (PPV) for development of clinical arthritis within two 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 two-year follow-up. Thus, CSA and information on autoantibodies is insufficient to accurately identify imminent autoantibody-positive RA.