4CPS-203 Real-life analysis of the development of anti-drug antibodies in adult 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 adult IBD patients undergoing therapeutic drug monitoring (TDM), along with therapeutic approach and potential factors contributing ADA development. <h3>Material and Methods</h3> Retrospective observational study in adult IBD patients treated with infliximab and adalimumab undergoing TDM, within January/2019 to September/2024. Adalimumab, infliximab and ADA concentrations were measured by chemiluminescence. Concretely, ADA if patients had infliximab≤3mcg/ml and adalimumab≤5mcg/ml concentrations (drug-sensitive assay). Standard dosage regimen(SD): adalimumab 40mg/14days, infliximab 5mg/kg/8weeks; intensified dosage involved either shortening interval or increasing dose. <h3>Results</h3> 729 patients were included. Specifically, 462(63.4%) received adalimumab and 267(36.6%) received infliximab. Adalimumab antibodies(AAA) were evaluated in 434 samples from 200(43.3%) patients treated with adalimumab; and infliximab antibodies(ATI) were evaluated in 391 samples from 160(59.9%) patients with infliximab. Adalimumab treatment group, 17(3.7%) patients developed AAA: mean age of 40.9(11.4) years, BMI 26.4(7.4) kg/m2 and including 9(52.9%) females. All patients with Crohn disease. Seven(41.2%) patients had been on adalimumab for &lt;1year. At the time of AAA detection, 6(35.3%) patients had adalimumab SD, and 6(35.3%) receiving immunosuppressants. Fourteen (82.4%) patients discontinued adalimumab, while 3(17.6%) with AAA of 22ng/ml, 133ng/ml and 107.9ng/ml underwent adalimumab intensification achieved AAA negativisation. Poor adherence was suspected in 7(41.2%) patients. Infliximab treatment group, 22(8.2%) patients developed ATI: mean age of 46.9(14.6) years, BMI 25.2(5.6) kg/m2 and including 9(37.5%) females. IBD diagnosed: Crohn disease in 13(59.1%) and ulcerative colitis in 9(40.9%) patients. Thirteen (59.1%) patients had been on infliximab for &lt;1year. At the time of ATI detection, 13(59.1%) patients had infliximab SD, and 12(54.5%) receiving immunosuppressants. Fifteen (68.2%) patients discontinued infliximab, while 6(27.3%) with ATI&lt;30ng/ml and 2(9.1%) with 100.6ng/ml and 171.7ng/ml underwent infliximab intensification achieved ATI negativisation. Poor adherence was confirmed in 6(27.3%) patients. Adalimumab and infliximab concentrations were &lt;1mg/ml in all patients with ADA. <h3>Conclusion and Relevance</h3> A proportion of IBD patients developed ADA, with a higher incidence observed in those receiving infliximab. Enhancing adherence could reduce the risk of ADA development, and intensifying treatment may be effective in achieving ADA negativisation. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest