Strategies to predict rheumatoid arthritis development in at-risk populations.

The development of RA is conceived as a multiple hit process and the more hits that are acquired, the greater the risk of developing clinically apparent RA. Several at-risk phases have been described, including the presence of genetic and environmental factors, RA-related autoantibodies and biomarkers and symptoms. Intervention in these preclinical phases may be more effective compared with intervention in the clinical phase. One prerequisite for preventive strategies is the ability to estimate an individual's risk adequately. This review evaluates the ability to predict the risk of RA in the various preclinical stages. Present data suggest that a combination of genetic and environmental factors is helpful to identify persons at high risk of RA among first-degree relatives. Furthermore, a combination of symptoms, antibody characteristics and environmental factors has been shown to be relevant for risk prediction in seropositive arthralgia patients. Large prospective studies are needed to validate and improve risk prediction in preclinical disease stages.