Abstract
The clinical and molecular heterogeneity of IBD-both between patients and within the same individual over time-continues to pose a significant challenge to the implementation of truly personalised treatment strategies. Unlike oncology, where somatic mutation patterns define an actionable information layer, IBD lacks detectable dominant molecular drivers that can guide therapeutic choices. Although the therapeutic landscape has broadened with the advent of numerous biologics and small molecule drugs, predictive (ex ante) biomarkers for treatment response remain elusive. In this review, we assess the current progress and limitations of biomarker-guided precision therapy in IBD. We argue that traditional binary response definitions at single landmark endpoints fail to reflect the multidimensional and dynamic nature of therapeutic outcomes. We hence propose combined, and thus individualised, endpoints such as comprehensive disease control as a more holistic and responsive therapy goal in IBD. We propose to integrate the individual longitudinal dynamics of treatment response, and also continuous, objective monitoring of subclinical residual inflammation, analogous to the concept of minimal residual disease in oncology. In this concept, longitudinal assessment of patient-reported outcomes and molecular profiling in response to therapy may serve as early predictors of long-term outcomes, guide early therapeutic adjustments and reveal mechanisms that open new therapeutic avenues, such as adjunct or combination treatments. Adopting this dynamic, data-driven approach to treatment adaptation could shift management of IBD from reactive to proactive and substantially improve long-term outcomes with the vision to fully control a life-long disease.