Papers of the Week

The field of rheumatology has made major contributions to medicine through the identification of cellular and molecular targets and with the development of therapies for the treatment of an impressive range of immune-mediated rheumatic diseases. In recent years new milestones have been achieved. These include the recognition of an "at risk" state, defined by distinct clusters of characteristics, including disease-specific autoantibodies in serum and symptom complexes that include inflammatory joint pain. Studies seeking to prevent high-risk individuals from progressing to a state of clinically apparent arthritis have been initiated. Here, exploiting the current evidence base, an experimental framework to inform trial design is described, taking into consideration study patient phenotypes and highlighting the impact of risk stratification and the options available for therapeutic intervention according to the different phases of the preclinical syndrome. Pragmatic primary end points and suggestions for a set of risk-focused trial outcome measures are proposed, including both clinical assessments and patient-reported outcome measures. Rheumatoid arthritis prevention studies provide an important experimental framework for generating deeper insights into risk stratification and for refining trial design in the future. To this end, a research agenda is suggested, together with some considerations for imaging and for biological sampling. This commentary concludes with some of the operational issues that arise from such studies and addresses some of the challenges associated with recruitment and retention of the at-risk trial participant.