Intestinal Ultrasound-Assessed Transmural Healing in Patients with Inflammatory Bowel Disease treated with Advanced Therapies: A Real-World Cohort Study

Background and aims: Transmural healing (TH) is increasingly recognised as a marker of deep inflammatory control in inflammatory bowel disease (IBD). Intestinal ultrasound (IUS) enables non-invasive, repeated assessment of bowel-wall inflammation, although disease- and treatment-specific patterns of transmural healing and response remain incompletely characterised. This study aimed to evaluate IUS-defined TH at week 52 in patients with Crohn's disease (CD) and ulcerative colitis (UC) initiating advanced therapies, exploring longitudinal outcomes, previous treatment exposure and the prognostic relevance of early ultrasound findings. Methods: This retrospective, single-centre study included 363 patients with active IBD (199 CD and 164 UC) initiating advanced therapy between October 2021 and June 2026. IUS outcomes were assessed at weeks 12, 24, 52, and 104. TH was defined as bowel-wall thickness (BWT) ≤3 mm and absent colour Doppler signal (CDS) in all evaluable intestinal segments, whereas transmural response (TR) was defined as a ≥25% reduction in BWT in the baseline index segment. Disease-specific outcome rates, treatment-related differences, longitudinal associations and exploratory predictors were evaluated. Results: At week 52, TH was achieved in 46/158 patients with CD (29.1%; 95% CI 22.6–36.6%) and 52/123 patients with UC (42.3%; 95% CI 33.9–51.1%). TR was more frequent, occurring in 84/156 (53.8%) and 79/123 (64.2%) patients, respectively. Although numerical differences in TH were observed across therapeutic classes, none remained statistically significant after correction for multiple comparisons. In both diseases, patients previously exposed to at least two advanced therapies showed lower TH rates than treatment-naïve patients. In contrast, TR rates were less markedly affected by previous advanced therapy exposure, with no statistically significant differences across exposure groups in either CD (56.6%, 56.0% and 49.1% for 0, 1 and ≥2 previous therapies, respectively; P=0.689) or UC (70.0%, 62.1% and 59.1%, respectively; P=0.525). Significant reductions in composite ultrasound activity scores were observed throughout follow-up in both diseases, with median BUSS reductions of 1.47 points in CD and MUC reductions of 3.64 points in UC at week 52 (both Holm-adjusted P<0.001). In exploratory CD regional assessments at week 52, colonic outcomes were numerically higher than terminal ileal outcomes (TH: 28/37 [75.7%; 95% CI 59.9–86.6%] vs 46/99 [46.5%; 95% CI 37.0–56.2%]; TR: 36/38 [94.7%; 95% CI 82.7–98.5%] vs 60/99 [60.6%; 95% CI 50.8–69.7%]), without significant paired regional differences after multiplicity adjustment. TH at week 12 was associated with TH at week 52 in CD (11/17 [64.7%] vs 10/43 [23.3%]; OR 6.05, 95% CI 1.79–20.51; Holm-adjusted P=0.046), with modest discrimination. In UC, the corresponding proportions were 14/19 (73.7%) vs 12/30 (40.0%) (OR 4.20, 95% CI 1.20–14.74; Holm-adjusted P=0.251). Conclusions: In this real-world IBD cohort, transmural healing was achieved in approximately one-third of evaluable patients with CD and two-fifths of those with UC at one year, whereas transmural response was more frequent. Previous advanced therapy exposure and early ultrasound findings may help characterise the likelihood of subsequent transmural healing. These findings support the complementary role of IUS in longitudinal disease monitoring and highlight the need for prospective studies to establish whether targeting transmural remission improves long-term outcomes beyond established therapeutic targets.