P381 Ustekinumab trough levels are associated with sonographic transmural healing in Pediatric Inflammatory Bowel Disease
Kellar, A.(1)*;Aronskyy, I.(1);Dubinsky, M.C.(1);Dolinger, M.T.(1);
(1)Icahn School of Medicine at Mount Sinai, Pediatric Gastroenterology- Susan and Leonard Feinstein IBD Clinical Center, New York, United States;
Transmural healing (TH) assessed by intestinal ultrasound (IUS) is associated with improved inflammatory bowel disease (IBD) outcomes. This study evaluates the relationship between ustekinumab trough levels (UTL) and sonographic TH in children with IBD treated with ustekinumab (UST).
Children (<18 years) with IBD treated with maintenance UST and undergoing IUS examination and serum UTL (Prometheus Labs, CA) at a single tertiary center between July 2020 and October 2022 were prospectively recruited. Children who underwent IUS and UTL on 2 events >6 months apart were included in a per-event analysis. Primary outcome was the comparison of UTL between children with and without TH, defined as bowel wall thickness (BWT) <3 mm and no hyperemia (BWH) on color Doppler, using the Mann-Whitney U test. Area under the receiver operating curve (AUROC) determined the optimal UTL cut-point to detect TH. Secondary outcome was the comparison of UTL for each IUS parameter. Descriptive statistics summarized the data as frequencies and percentages for categorical variables and median [interquartile range] for continuous variables. A p-value of significance was set to <0.05.
Overall, 50 IUS exams on 129 bowel segments were performed in 44 children with IBD, 34:10 Crohn’s disease (CD):ulcerative colitis (UC)/IBD-U treated with UST, median [IQR] age 14.9[13.2-16.6] years, 22(50%) female, and disease duration 3.83[1.98-5.32] years (Table 1). 18(41%) children were treated with standard dose UST of 90mg every 8 weeks and had significantly lower UTL compared to 26(59%) treated with escalated dosing of 90 mg every 4 or 6 weeks (7.4[4.8-12.7] ug/ml vs. 11.6[6.1-19.3] ug/ml, p=0.002). Median time between UTL and IUS was 0 days [0-11.25]. Overall, 24(55%) children (18(53%) CD, 6(60%) UC/IBD-U) achieved TH. Higher UTL was associated with TH (13.1[6.1-17.5] ug/ml) compared to children without TH (5.7[4.2-13.9] ug/ml; p=0.010) (Figure 1A). Higher UTL was also associated with TH in children with CD (11.7[5.3-17.0] ug/ml) compared to children with CD without TH (5.5[4.2-11.0] ug/ml; p=0.013) (Figure 1B). Optimal UTL cut-point to detect TH was 11.4 ug/ml for all children (AUROC=0.647, sensitivity=62%, and specificity=69%) and children with CD (AUROC=0.661, sensitivity=59%, specificity=79%). Median UTL for all children was associated with lymphadenopathy (p=0.02) but no other individual IUS parameters (Table 2).
Higher maintenance UTL are associated with sonographic TH in children with IBD. Future prospective studies are needed to determine if targeting higher UTL levels during induction and maintenance UST therapy promotes TH.