<p>Preventive interventions in patients at increased risk of developing rheumatoid arthritis (RA) have gained in importance in recent years. Current study data show that early, targeted immunomodulatory treatment in carefully stratified high-risk patients can delay the onset of clinically manifest RA and reduce the disease burden in the sense of secondary prevention. This review summarizes the evidence from four key studies and discusses their clinical implications, taking the particular legal and practical challenges associated with off-label use into account.</p>