Windows for intervention in the prearthritis phase of rheumatoid arthritis? A narrative review of key triggering events and potential preventive strategies.

Rheumatoid arthritis (RA) is an autoimmune disease that often evolves over several years, which in the presence of risk factors, is termed the at-risk phase. Several of the currently approved treatments for RA have been evaluated for the prevention of RA during the at-risk phase, but without showing effects sufficient to warrant their use prior to diagnosis. There is an ongoing surge in research efforts to understand mechanisms underlying the onset of RA, in particular concerning deviations in the adaptive immune system and the role of mucosal surfaces in the breach of self-tolerance and triggering of arthritis. With this focus, we here aimed to review current knowledge on RA development prior to arthritis onset. Also, since the pre-arthritis phase may contain windows of opportunity to prevent RA onset, we present and conceptualise different strategies to potentially interfere with steps leading to RA. While the body of knowledge is increasing, our understanding of RA development remains incomplete, and available studies highlight that RA appears similarly heterogeneous prior to onset as is seen after diagnosis. Hence, the timing and the selection of subjects will be crucial for the success of future potential interventions.