Incidence and Radiographic Progression of Rheumatoid Arthritis in Anti-Citrullinated Protein Antibody-Positive Individuals: A Six-Year Population- Based Cohort Study.

Abstract

Objectives: Anti-citrullinated protein antibodies (ACPA) predict rheumatoid arthritis (RA) and radiographic joint destruction. However, data on long-term outcomes in ACPA-positive individuals without RA are limited. This study aimed to investigate the six-year cumulative incidence of RA and radiographic progression among ACPA-positive individuals without RA at baseline in a population-based cohort.

Method: A total of 1,541 participants without RA at baseline were enrolled from the population-based cohort, of whom 28 tested positive for ACPA. Incident cases of RA were identified based on participants' self-reported physician diagnosis and medication history over a six-year follow-up period. Radiographic progression in the hands was assessed using the van der Heijde modified Sharp score.

Results: Five participants developed RA within the first three years, including three who were ACPA-positive at baseline (all with high ACPA titers). After 3 years, additional RA cases were identified only among participants who were ACPA-negative at baseline, whereas no further cases occurred among those who were ACPA-positive at baseline. The positive predictive value (PPV) of ACPA for RA within three years was 15.0%, rising to 30.0% among those with high ACPA titers. When combined with rheumatoid factor or matrix metalloproteinase-3, the PPV further increased. Radiographic progression occurred in all participants with high-titer ACPA who developed RA (n =3) and in one ACPA-positive individual without RA, but not in ACPA-negative individuals who developed RA.

Conclusions: ACPA positivity, particularly at high titers, may be associated with an increased risk of incident RA and with radiographic bone destruction, even in the absence of clinical symptoms or RA diagnosis.