4CPS-215 Real-life analysis of the development of anti-drug antibodies in paediatric patients with inflammatory bowel disease and therapeutic approach

<h3>Background and Importance</h3> Loss of response to infliximab and adalimumab therapy may occur due to development of anti-drug antibodies (ADA), leading to treatment failure in inflammatory bowel disease (IBD). <h3>Aim and Objectives</h3> To assess the immunogenicity of infliximab and adalimumab in paediatric IBD patients, along with therapeutic approach and potential factors contributing ADA development. <h3>Material and Methods</h3> Retrospective observational study in paediatric IBD patients treated with infliximab and adalimumab undergoing therapeutic drug monitoring (TDM), within January 2019 to September 2024. Adalimumab, infliximab and ADA concentrations were determined by enzyme-linked immunosorbent assay (ELISA) until May 2022, followed by chemiluminescence immunoassay (CLIA). Concretely, ADA if patients had infliximab ≤ 3mcg/ml and adalimumab ≤ 5mcg/ml concentrations (drug-sensitive assay). Treatment was initiated according to the standard dosing regimen (SD) for adalimumab and infliximab in paediatrics and was adjusted according to TDM; dose intensification consisted of shortening the interval or increasing the dose. <h3>Results</h3> Ninety patients were included. Specifically, 38 (42.2%) received adalimumab and 52 (57.8%) received infliximab. Adalimumab antibodies (AAA) were evaluated in 33 samples from 10 (26.3%) patients treated with adalimumab; and infliximab antibodies (ATI) were evaluated in 53 samples from 28 (53.8%) paediatrics treated with infliximab. No patients underwent adalimumab treatment were detected developing AAA. Infliximab treatment group, four (7.7%) patients developed ATI: mean age of 12.9 (7.1) years and including three (75.0%) females. IBD diagnosed: Crohn’s disease in two (50.0%) patients and ulcerative colitis in two (50.0%) patients. Two (50.0%) patients had been on infliximab for &lt;1 year. At the time of ATI detection, all of them were on treatment with an intensified infliximab dosage, and three (75.0%) receiving immunosuppressants. Two (50.0%) patients discontinued infliximab, while two (50.0%) with ATI 22 ng/ml and 137 ng/ml underwent infliximab intensification achieved ATI negativisation. Infliximab concentrations before antibody detection (&lt;6 months) were 1.5 µg/ml, 3.6 µg/ml and 5.9 µg/ml. One patient was in induction and had previously received infliximab. No poor patient adherence was detected. HLA-DQA1*05 genetic variants were analysed in three (75.0%) patients, two (66.7%) patients were HLA-DQA1∗05 carriers. Adalimumab and infliximab concentrations were &lt;1mg/ml in all patients with ADA. <h3>Conclusion and Relevance</h3> A proportion of IBD paediatric patients developed ADA, with a higher incidence observed in those receiving infliximab. Intensifying treatment may be effective in achieving ADA negativisation, in some cases. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest