4CPS-044 Proactive monitoring of infliximab in paediatric inflammatory bowel disease over a 4-year period

<h3>Background and Importance</h3> Preliminary data suggest that proactive therapeutic drug monitoring (TDM) guides dose adjustment to achieve appropriate trough concentrations (Cmin), reducing the risk of treatment failure (TF) and improving safety. <h3>Aim and Objectives</h3> To analyse the experience of a multidisciplinary proactive TDM programme for infliximab (IFX) dose adjustment in paediatric patients with inflammatory bowel disease (IBD) (Crohn’s disease (CD) and Ulcerative Colitis (UC)). <h3>Material and Methods</h3> Prospective, single-centre study including children with IBD treated with IFX from September 2019 to September 2023. Demographic, clinical, analytical and pharmacotherapeutic monitoring variables were collected. IFX Cmin and anti-infliximab antibodies (ATI) were determined by ELISA or chemiluminescence. Dose individualisation was performed using the population pharmacokinetic model of Fasanmade et al., (2011), implemented in NONMEM v7.4.3. IFX Cmin was monitored at induction and every 6 months thereafter. Efficacy endpoints were: TF, IBD-related surgery and hospitalisation. Finally, adverse reactions (ARs) were recorded. <h3>Results</h3> Thirty-three patients were included, 21 male. Eighteen with CD and 15 with UC. The median (interquartile range (IQR)) age at diagnosis was 11.58 (6.87–14.04) years. There were 794 administrations with a mean (SD) dose of 8.66 (2.22) mg/kg. The mean (SD) IFX Cmin was 25.71 (19.50) µg/ml at weeks 1–3, 13.63 (7.73) µg/ml at weeks 6–7, 14.60 (8.01) µg/ml at week 14 and 10.47 (8.47) µg/ml at maintenance. A total of 106 dose adjustments were made out of 290 (36.55%) IFX Cmin. Regarding efficacy, 6 (18.18%) patients had TF during the 4 years of follow-up; 2 primary and 4 secondary TF. TF was due to: 1) pharmacodynamic failure (66.67%); 2) severe infusion reaction related to ATI (16.67%); and 3) other ARs (16.67%). Six (18.18%) patients were hospitalised, 62.50% of the admissions were for IBD complications and 37.50% AR. Four (12.12%) patients had emergency visits, 100% due to ARs. Thirty-nine ARs were recorded: 23.08% infusion reactions, 61.54% infections and 15.38% paradoxical psoriasis; 48.72% of the ARs were classified as severe. Two patients had ATIs, one reversed by intensifying treatment. One (3.03%) patient underwent colectomy. <h3>Conclusion and Relevance</h3> Multidisciplinary proactive TDM programme has allowed to successfully adjust IFX doses in paediatric patients, obtaining promising clinical results similar to those reported in adults (Papamichael et al. 2017 and Sánchez-Hernández et al. 2020). <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest