30

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

Speakers


Tracks

Related Products

Thumbnail for IBD Diagnosis. Monitoring, and Prediction of Complications
IBD Diagnosis. Monitoring, and Prediction of Complications
SOCIETY: AGA This session highlights the latest research on novel prediction models in IBD as well as the role of the fecal microbiome and imaging in IBD…
Thumbnail for EFFICACY AND SAFETY OF OBEFAZIMOD IN UC PATIENTS AT WEEKS 48 AND 96 OF AN OPEN-LABEL MAINTENANCE STUDY AMONG CLINICAL RESPONDERS AT WEEK 8 OF THE PHASE 2B INDUCTION TRIAL
EFFICACY AND SAFETY OF OBEFAZIMOD IN UC PATIENTS AT WEEKS 48 AND 96 OF AN OPEN-LABEL MAINTENANCE STUDY AMONG CLINICAL RESPONDERS AT WEEK 8 OF THE PHASE 2B INDUCTION TRIAL
Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with moderately to severely active ulcerative colitis (UC) [1]…
Thumbnail for PREGNANCY OUTCOMES AFTER MATERNAL OR PATERNAL EXPOSURE IN THE TOFACITINIB ULCERATIVE COLITIS CLINICAL PROGRAM
PREGNANCY OUTCOMES AFTER MATERNAL OR PATERNAL EXPOSURE IN THE TOFACITINIB ULCERATIVE COLITIS CLINICAL PROGRAM
BACKGROUND: Pregnant women with ulcerative colitis (UC) have a higher risk of adverse pregnancy outcomes vs age-matched controls.1 Tofacitinib is an oral Janus kinase inhibitor for the treatment of UC. There are no well-controlled studies on tofacitinib use in pregnant women…
Thumbnail for THE EFFECT OF NLRX1 ACTIVATION ON EOSINOPHILS IN ULCERATIVE COLITIS AND INFLAMMATION: TRANSLATIONAL LEARNINGS ACROSS DISEASES AND FROM MOUSE TO HUMAN
THE EFFECT OF NLRX1 ACTIVATION ON EOSINOPHILS IN ULCERATIVE COLITIS AND INFLAMMATION: TRANSLATIONAL LEARNINGS ACROSS DISEASES AND FROM MOUSE TO HUMAN
Background: Although the precise role of eosinophils in IBD is debated, elevated eosinophils may influence response to therapy and clinical outcomes1. Thus, therapeutic agents which affect both neutrophil and eosinophil recruitment may provide more robust clinical improvement in patients with UC…