Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory disease of joints in childhood. Despite novel therapeutic options, a number of children with JIA do not achieve an inactive disease, resulting in a lifelong burden. We will focus on these particularly sick children. In our well-established longitudinal cohorts of all participating countries (Canada, the Netherlands, Germany, Sweden, Italy) we have collected detailed data (information of patient history) and blood samples. From this data, we will identify the subgroup of high-risk children and perform an analysis on immune cells of the blood and arthritic joints using novel analytical methods (Fig. 1.) together with available patient data (Fig 2.) to identify mechanisms and origins of the disease. We will also integrate data on socio-economic background, including regional differences in access to medications, to see whether this affects therapeutic success (Fig. 3 and 4.). Using this approach we will identify and evaluate disease markers prospectively in new patients of our cohorts. Our consortium will thereby characterise key pathways – biological, clinical and societal, which predict therapeutic response and identify those patients with a particular risk for developing a severe disease. This is the first stop towards a personalised medicine approach to tailor individualised strategies to improve outcome for affected children with JIA.