P0956Infliximab trough concentrations are associated with paediatric sonographic transmural healing targets in children with Inflammatory Bowel Disease

Abstract Background Transmural healing (TH) is an emerging treatment target for IBD and is associated with superior outcomes compared to clinical or endoscopic healing. However, current paediatric proactive infliximab (IFX) therapeutic drug monitoring (pTDM) guidelines are based on clinical and biochemical outcomes. This study aimed to identify IFX trough concentration (cTrough) targets associated with TH assessed by intestinal ultrasound (IUS). Methods This cohort study included paediatric IBD patients, 18 years of age, who started IFX and underwent IUS as part of routine clinical care. Patients with isolated upper GI disease, proctitis or no IUS follow-up were excluded. The primary outcome was the IFX induction cTrough associated with TH, defined as a maximum bowel wall thickness (BWT) 2.5mm per paediatric consensus and compared with the adult 3.0mm definition (+/- colour doppler signal). IUS was conducted following the International Bowel UltraSound (IBUS) acquisition consensus by two IBUS-certified paediatric gastroenterologists. IFX cTrough and antibodies (ATIs) were measured at the 3rd and 4th infusion and at maintenance intervals following pTDM guidelines. IFX and ATIs were measured by LC-MS/MS and ECLIA, respectively (Mayo Clinic Laboratories). Area under the receiver operating characteristics (AUROC) analyses were used to evaluate IFX cTrough cutoffs associated with TH. Results The cohort included 66 children with IBD, 45 of whom met inclusion criteria (67 IFX cTrough-IUS pairs). Mean age 10 (IQR: 9-13) years of age, 53% (24) Crohn’s disease, and 58% (26) female. Patients with the paediatric TH target (BWT 2.5mm) had a higher median IFX induction cTroughs 39.5 μg/mL (24.5-50) compared to ≥ 2.5mm, 14 μg/mL (7.6-26.5; P=0.04). Patients with a maximum BWT 3.0 mm had higher IFX induction cTroughs 32 μg/mL (25-49) compared to ≥ 3.0mm, 14 μg/mL (7.6-23; P=0.03). At infusion-3, an IFX ≥22 μg/mL cutoff predicted TH (AUROC 0.74; sensitivity 0.80, specificity 0.80) for 2.5mm and (AUROC 0.78; sens 0.83, spec 0.89) for 3.0mm. At infusion-4, a cutoff of IFX ≥17 μg/mL (AUROC 0.75; sens 1.00, spec 0.71) predicted the paediatric TH target at 2.5mm, while a cutoff of IFX ≥14 μg/mL (AUROC 0.82; sens 1.00, spec 0.75) predicted TH at the adult 3.0mm definition. Addition of colour doppler signal to BWT did not improve AUROC predictions. Moreover, maintenance IFX concentrations beyond infusion-4 did not predict TH. Conclusion This study identified IFX cTroughs that predict paediatric transmural healing by intestinal ultrasound. Maintenance concentrations did not predict healing. Future intervention studies should evaluate if prospective optimized dosing results in enhanced transmural healing outcomes. Conflict of interest: Toroslu, Ertug: NOTHING TO DECLARE Patel, Perseus: None Colman, Ruben: No conflicts