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Background and Importance Therapeutic drug monitoring (TDM) of biologic therapies such as ustekinumab is increasingly recognised as a valuable tool in the management of inflammatory bowel disease (IBD). Insufficient serum concentrations and the formation of anti-drug antibodies (ADA) can impair treatment efficacy and patient safety. Nevertheless, routine ustekinumab monitoring has not yet been widely implemented, and data supporting its systematic use remain limited. Characterising pharmacokinetic variability and immunogenicity may help optimise therapeutic outcomes and enhance disease control.Aim and Objectives The aim of this study was to evaluate the usefulness of systematic pharmacokinetic monitoring of ustekinumab in IBD, focusing on the detection of ADA, identification of trends in drug levels, and assessment of clinical and biomarker responses after therapeutic adjustments.Material and Methods A retrospective observational study was conducted in a tertiary hospital between January 2023 and March 2025. Adult patients treated with ustekinumab for Crohn’s disease or ulcerative colitis were included. Demographic and clinical data (disease duration, smoking history, previous surgery, and perianal involvement) were recorded. Ustekinumab and ADA serum concentrations, faecal calprotectin (FC), C-reactive protein (CRP), and Harvey-Bradshaw Index (HBI) were collected. Therapeutic regimens, interventions after reduced drug levels, and subsequent biomarker evolution were analysed. Quantitative variables were expressed as mean±SD and qualitative variables as frequencies or percentages.Results 20 patients (55% female, mean age 51.4±16.7 years) were included; 70% had Crohn’s disease and 30% ulcerative colitis, with a mean disease duration of 12.0±8.7 years. All patients had undetectable ADA (<0.3 AU/mL). 16/20 (80%) presented reduced ustekinumab levels (mean 0.21±0.17 µg/mL) accompanied by elevated FC (1502.5±2024.7 µg/g) and CRP (9.4±9.5 mg/L). After dose intensification or intravenous reinduction, FC and CRP decreased in 20% and 30% of patients, respectively, and 90% achieved higher ustekinumab levels post-intervention.Conclusion and Relevance Although ADA were absent, subtherapeutic ustekinumab concentrations were frequent and associated with inflammatory activity. Routine pharmacokinetic monitoring may facilitate early detection of reduced exposure, guide individualised dose optimisation and improve treatment efficacy.Conflict of Interest No conflict of interest