PharmacogenOmics to Optimize Steroid Treatment in Children

The incidence of paediatric inflammatory diseases is increasing globally, with a notably younger age of onset. High-dose glucocorticoids (GC) remain the most accessible and commonly used anti- inflammatory treatment for these conditions. However, evidence-based guidance for pulse GC therapy is limited, particularly regarding the optimal duration and the ability to predict patient responsiveness and toxicity. Moreover, epigenetic, metabolic, and immunological sequelae of high- dose GC in children remain poorly understood. In the PhORECaST project, we pursue a multi-center, multi-omics study to compare the clinical efficacy and long-term outcomes of a 3-day vs. 5-day pulse of high-dose GC in children with acute immune-mediated disorder. The goal is to identify biomarkers that predict individual response and risk of toxicity, and to lay the groundwork for evidence-based treatment algorithms integrating alternative targeted therapies when GC is likely to be ineffective or harmful. We will collect data at three timepoints: (1) baseline, (2) 3-days after first GC pulse, and (3) at 3- month follow up. We will link clinical, conventional laboratory, and patient-reported outcomes with system-level analyses of transcriptomic, proteomic, metabolic, and epigenetic changes. We anticipate delivering a robust predictive framework and guidelines that can be rapidly translated into clinical practice, thereby personalizing treatment approaches for acutely ill children with immune-mediated diseases. This project is a collaboration between paediatric specialists, immunologists, systems biologists, and patient representatives to benefit children with immune diseases undergoing GC therapy.

No additional funding sources recorded.