Fabrizio Fanizzi, Alessandra Zilli, Tommaso Lorenzo Parigi, Virginia Solitano, Sara Massironi, Federica Furfaro, Laurent Peyrin-Biroulet, Mariangela Allocca, Silvio Danese, Ferdinando D'Amico
Background: The therapeutic paradigm of Crohn's disease (CD) has progressively evolved from symptom control toward objective treatment targets aimed at modifying disease course. Although endoscopic mucosal healing (MH) is currently regarded as a major treatment goal, it may inadequately reflect residual inflammation in a condition characterized by transmural bowel involvement. Consequently, transmural healing (TH), assessed through cross-sectional imaging modalities, has emerged as a potential marker of deeper disease control. Methods: A comprehensive literature review was conducted to identify studies evaluating the definition, assessment, prognostic significance, and achievability of TH in CD. Original studies, randomized controlled trials, systematic reviews, consensus statements, and international guidelines were included. Results: Accumulating evidence indicates that TH is associated with superior long-term outcomes compared with MH alone, including lower risks of hospitalization, surgery, treatment escalation, disease relapse, and bowel damage progression. However, substantial heterogeneity persists regarding the definition of TH across imaging modalities, with intestinal ultrasound and magnetic resonance enterography representing the principal tools for its assessment. Available data suggest that TH can be achieved in a meaningful proportion of patients receiving advanced therapies, particularly when treatment is initiated early in the disease course, although rates vary considerably according to therapeutic class, disease characteristics, and the definition adopted. Emerging technologies may further refine the assessment of transmural disease activity. Conclusions: TH represents a promising therapeutic target that may better capture the full burden of inflammation in CD than mucosal endpoints alone. Future efforts should focus on harmonizing imaging criteria and determining whether targeting TH can translate into meaningful disease modification and improved long-term outcomes.