Autoantibodies are major predictors of arthritis development in patients with anti-citrullinated protein antibodies and musculoskeletal pain.

: Predictors of arthritis development are highly warranted among patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms to optimize clinical management. We aimed to identify clinical and laboratory predictors of arthritis development, including biochemically assessed alcohol consumption, among ACPA-positive patients with musculoskeletal pain.: 82 ACPA-positive individuals with musculoskeletal pain but no clinical arthritis were followed for a median of 72 months (interquartile range 57-81 months). We evaluated the prognostic value of baseline clinical and laboratory factors including smoking, symptom duration, age, gender, shared epitope, rheumatoid factor (RF), anti-carbamylated protein antibodies, ACPA levels, erythrocyte sedimentation rate, C-reactive protein levels, tender joint count, patient-reported general well-being, 28-joint Disease Activity Score, and alcohol consumption as measured by phosphatidyl ethanol (PEth) levels in whole blood.: During follow-up, 48% developed at least one arthritis. Multivariable analysis revealed an increased risk of arthritis development with RF positivity [hazard ratio (HR) = 2.3, 95% confidence interval (CI) 1.1-4.8, p = 0.028] and higher ACPA levels (HR = 1.0, 95% CI 1.000-1.001, p = 0.002). High levels of RF (HR = 4.4, 95% CI 1.7-11) entailed the highest HR in this ACPA-positive population. Neither clinical characteristics nor alcohol consumption measured by PEth conferred significant prognostic value.: ACPA levels and concurrent presence of RF are independent predictors of arthritis development among ACPA-positive patients with musculoskeletal pain. The results are compatible with a dose-response relationship between RA-related autoantibodies and risk of arthritis development.