Predicting Rheumatoid Arthritis in At-risk Individuals

The typical evolution of rheumatoid arthritis (RA) is that a person with genetic risk factors develops autoantibodies and subclinical inflammation under relevant environmental influences, culminating in symptoms and finally clinically detectable arthritis. Because several of these characteristics can be present before the outbreak of clinical arthritis, it is possible to study the at-risk phase (the presence of ≥1 risk factors for RA in an individual) with the aim of quantifying the risk for that individual. As a person progresses through the different phases of disease development, different markers can be used for prediction. In the early asymptomatic phase, genetics, environmental factors, and autoantibodies are relevant, whereas in later phases additional markers, such as symptoms and imaging, come into play, conveying the risk of not only RA but sometimes even of imminent RA. Prediction is of limited use when not coupled with the possibility to intervene and lower the risk of RA. There is a clear need for effective preventive strategies that take the phase of disease development into account. On the other hand, selecting the right persons for preventive treatment according to their stage of disease development requires the improvement of current prediction models and strategies. This commentary presents an overview of risk factors and their combination into prediction models for use in different stages of RA development. Although clear progress has been made and assuming a future with effective options to intervene, there are still several gaps in our knowledge that need to be filled before it is clear who should be tested and when.