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EARLY INTESTINAL ULTRASOUND RESPONSE TO BIOLOGIC AND SMALL MOLECULE THERAPY PREDICTS ENDOSCOPIC OUTCOMES IN CHILDREN WITH ULCERATIVE COLITIS

Date
May 18, 2024

Introduction: Stride-II recommends early biomarker targets for treatment optimization to achieve treat-to-target (T2T) endoscopic remission (ER) in ulcerative colitis (UC). Predictive capabilities of intestinal ultrasound (IUS) for T2T ER remains unknown. We aimed to evaluate IUS response to predict endoscopic outcomes in children with UC.

Methods: Prospective, longitudinal cohort study of children (<18 years) with moderate-to-severe UC (endoscopic Mayo score (EMS >2)) starting biologic or small molecule treatment were included. Children were evaluated at baseline, 8+2 weeks, and after 6-12 months at T2T endoscopy by IUS (bowel wall thickness (BWT), color Doppler signal (CDS), International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), and Civitelli UC Index (CUCI)), clinical (Pediatric Ulcerative Colitis Activity Index (PUCAI)), and biochemical (fecal calprotectin (FC) and C-reactive protein (CRP)) assessments. T2T ER was defined as EMS=0, endoscopic improvement (EI) as EMS<1, and response as EMS decrease >1. Primary outcome was accuracy of change in BWT between baseline and week 8 to detect ER. Secondary outcomes were change between baseline and week 8 for BWT, IUS scores, PUCAI, FC, and CRP to detect all endoscopic outcomes, accuracy of T2T BWT to detect ER and EI, and correlation of T2T assessments with EMS. Descriptive statistics summarized the data and univariate analyses tested associations. Area under the receiver operating curve (AUC) analysis determined cut-off values and correlation was analyzed with Spearman’s correlation coefficient.

Results: 42 children (median age 14 [IQR 12-17] years, 25 (59%) biologic naïve) were included, 21 (50%) achieved ER, an additional 9 (21%) achieved EI only, and 2 (2%) endoscopic response only (Table 1). A >43% decrease in BWT at week 8 predicted ER with an AUC of 0.72 [95% CI 0.56-0.88], EI with an AUC of 0.74 [95% CI 0.55-0.93], and endoscopic response with an AUC of 0.66 [95% CI 0.44-0.87]. At week 8, a >64% decrease in IBUS-SAS had the highest accuracy to detect ER (AUC 0.74 [95% CI 0.59-0.90]), a CUCI decrease by >1 point had the highest accuracy to detect EI (AUC 0.86 [95% CI 0.73-0.99]), and a >55% decrease in PUCAI had the highest accuracy to detect endoscopic response (AUC 0.83 [95% CI 0.66-0.99]; (Table 2)). T2T BWT <2.2 mm detected ER with an AUC of 0.91 [95% CI 0.82-1.00], 95% sensitivity and 91% specificity and a BWT <2.8 mm detected EI with an AUC of 1.0. BWT (ρ=0.78), IBUS-SAS (ρ=0.79), CUCI (ρ=0.84), FC (ρ=0.79), and PUCAI (ρ=0.73) strongly, CDS (ρ=0.42) moderately, and CRP (ρ=0.35) weakly correlated with EMS.

Conclusions: Early changes on IUS, BWT in particular, are highly accurate to predict endoscopic outcomes in children with UC. Our findings suggest that IUS could be used for treatment optimization and tight control to guide T2T strategy.

Presenter

Speaker Image for Michael Dolinger
Icahn School of Medicine at Mount Sinai Department of Pediatrics

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