Grant: Operating Grant

Early inflammatory polyarthritis (EPA) describes recent-onset disease with signs of inflammation in at least 3 peripheral joints, typically starts between 40 and 55 years of age, affects up to 5% of adults over their lifetime, and results in persistent inflammatory arthritis in close to 2% (30-50% of EPA). EPA patients are clinically very similar at onset, and their prognosis remains ill-defined and frequently poor, despite the availability of effective medications and the use of remission-targeted strategies. The lack at baseline of effective prognostic markers to identify patients needing these interventions is in part responsible for missing the window of opportunity for treatment in many patients. Based on previous observations that individuals segregate into poor and good in vitro activators of bone cells called osteoclasts (OC), we propose to identify characteristics of OC precursors and of OCs formed in vitro from patients' blood cells to correlate these characteristics with severe joint damage. As RA patients have short-for-age telomeres (i.e. DNA sequences at the ends of chromosomes), we propose to determine whether short telomeres at baseline (and rapidly shortening telomeres soon thereafter) are independent predictors of severe RA-like disease in EPA patients. We will also define the role of ultrasound joint evaluation in patients who do not have bone erosions on Xrays to predict which ones will develop severe joint damage. Finally, we will look at variants of immune-related genes and at the psychosocial characteristics (e.g. depression, coping strategies, pain perception) that may predict poor pain improvement and poor outcomes. The combination of these prognostic markers will lead to a prognostic tool that may guide early treatment (both biomedical and psychosocial) targeted to those patients most likely to benefit (cost-saving) and avoid unnecessary exposure to expensive and potentially toxic drugs when these are not needed.