P531 A model-based tool for guiding infliximab induction dosing to maximise long-term deep remission in children with inflammatory bowel diseases
نویسندگان
چکیده
Abstract Background Adequate infliximab (IFX) concentrations during induction treatment are predictive for deep remission (corticosteroid-free clinical and endoscopic remission) at six months in children with Crohn’s disease (CD) ulcerative colitis (UC).1 Under standard IFX dosing, often have low trough concentrations.2 Model-informed precision dosing (MIPD) is advocated as a promising strategy. We aimed to develop validate an MIPD framework guiding paediatric treatment. Methods Data from 31 (4-18 years, 15-76 kg, 20:11 CD:UC) receiving (5 mg/kg week [w]0, w2, w6) were repurposed.1 Eight population pharmacokinetic models evaluated (six 2-compartment two 1-compartment models). Modelling simulation used identify exposure targets, optimal sampling strategy, multi-model prediction algorithm implementation into software tool.3 A role clearance monitoring was evaluated. Results total of 251 available (6-10 samples per patient). One patient had undetectable w6 w12 but no measurable antibodies (ATI). At after start the treatment, 58% (18/31) patients achieved remission. The measured concentration best predictor classifier 7.5 mg/L target associated 64% probability (Figure 1). With less than 80% simulated <40 kg attained this 2). Immunomodulator combo-therapy only subtly improved attainment. Presence ATI lowered attainment considerably. most accurately precisely by implementing using concentration. outperformed single when optimising dose based on combined w2 w4 concentrations. resulted biased imprecise predictions. performance robust misspecification status. clearances (P=0.02) 3). An module added TDMx tool facilitate (https://tdmx.shinyapps.io/Infliximab_paediatric/). Conclusion freely available, interactive, provided improve rates CD UC. 1van Hoeve et al. J Pediatr 2022. 2van Rheenen Crohns Colitis 2020. 3Kantasiripitak CPT:PSP
منابع مشابه
WGO HANDBOOK ON GUT MICROBES 3 Probiotic Therapy for Induction and Remission in Inflammatory Bowel Diseases
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ژورنال
عنوان ژورنال: Journal of Crohn's and Colitis
سال: 2023
ISSN: ['1876-4479', '1873-9946']
DOI: https://doi.org/10.1093/ecco-jcc/jjac190.0661