Predictors of arthritis development in individuals at risk of rheumatoid arthritis: a 5-year follow-up study from a large cohort

The aim of this study was to predict rheumatoid arthritis (RA) development in a cohort of at-risk individuals with arthralgia positive for anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (IgM-RF), followed for up to 5 years. In total, 617 seropositive arthralgia individuals were included in the study. The ability of clinically and biologically relevant baseline characteristics to predict RA development was assessed using Cox proportional hazard regression analysis. Thirty-eight percent of study population was IgM-RF-positive, 31% was ACPA-positive, and 30% was positive for both ACPA and IgM-RF. Mean (SD) time till arthritis was 19.6 (19.0) months in 33.7% of participants; mean (SD) follow-up time of individuals who did not develop arthritis was 47.3 (24.5) months. We found that first-degree relatives of RA (hazard ratio [HR] = 1.50), individuals who had intermittent symptoms (HR = 1.64), symptoms for less than 12 months at inclusion (HR for symptom duration >12 months = 0.71), morning stiffness ≥1 hour (HR = 1.63), or reported joint swelling (HR = 1.51) independently had higher risk to develop arthritis. Moreover, individuals with high ACPA titres (HR = 4.65) or double positivity for ACPA and IgM-RF (HR = 6.83) had the highest risk of developing RA, as compared to those with only IgM-RF or low ACPA titres. The risk of developing arthritis was 58.2% when at least 3 variables were present. Baseline characteristics can be used to predict future RA development in seropositive arthralgia individuals. These results will aid in the identification of individuals at highest risk of developing RA, who could potentially benefit from additional follow-ups in clinical practice and recruitment in preventive trials.