Supplementary file 1_Multimodal biomarkers and prediction models for stricturing and penetrating progression in Crohn's disease.docx

Genomic scores, plasma and stool proteins, tissue transcriptomics, shear-wave elastography, radiomics, and machine-learning models suggest potential value for multimodal risk stratification, but most lack independent external validation, calibration, transportability, and demonstrated incremental value over routinely available clinical variables. Direct prospective evidence is substantially more developed for B2 stricturing progression than for incident internal B3 penetrating progression; internal penetrating disease and perianal fistulizing disease are treated as distinct outcomes.

Mechanistic studies suggest divergent fibrostenotic and tissue-destructive programs that provide biological guidance for biomarker selection. No biomarker or multimodal model identified in this review was ready to support routine biomarker-guided treatment escalation. Future studies should use well-characterized B1 baselines, prespecified structural outcomes, and prospective decision-impact testing that quantifies overtreatment.</p>