Dynamic profiling in inflammatory Bowel disease: A manifesto for personalized care

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a heterogeneous chronic condition whose clinical management has been advanced by the availability of molecularly targeted therapies. Despite this progress, marked inter- and intra-patient variability limits the effectiveness of a one-size-fits-all treatment approach. Precision medicine is a promising solution, but its implementation in routine care is limited. In this manifesto, we propose a multidimensional conceptual framework for the dynamic clinical profiling of IBD patients to be used in real-world clinical settings. Here, we first review key aspects of gut mucosal immunology, including epithelial-immune-stromal interactions and "angry" immune cells as mechanistic drivers of therapeutic variability. We then discuss five domains that are critical for clinical decision making in IBD: disease complexity (phenotype, history, and prior therapeutic exposure); patient frailty and comorbidities; extraintestinal manifestations; patients' needs and preferences; and sustainability. Integrating these domains into a treat-to-target strategy requires the iterative reassessment of patients and the acknowledgment of the evolving nature of both the disease and the patient. We then provide general recommendations for incorporating these elements into the choice of therapy. Finally, we argue that future IBD care should merge the analysis of composite molecular signatures with holistic, patient-centered, dynamic clinical profiling to guide treatment choice, monitoring, and de-escalation. By reframing personalized medical care as a continuous process - a dynamic profiling - rather than a static assessment, this framework should optimize therapeutic outcomes, enhance patients' quality of life, and improve the sustainability of IBD care.