4CPS-232 Ustekinumab trough levels and their impact on clinical and analytical results in Crohn’s disease

<h3>Background and Importance</h3> Ustekinumab has emerged as an effective treatment for moderate to severe Crohn’s disease (CD). However, limited data exist correlating ustekinumab serum levels with clinical remission, and its therapeutic range remains unclear. <h3>Aim and Objectives</h3> To analyse the relationship between trough ustekinumab concentrations at maintenance and clinical and analytical response of patients with CD. <h3>Material and Methods</h3> Observational, retrospective, multicentre study of adult patients with CD without perianal involvement treated with ustekinumab, who had trough serum levels monitored between April 2019 and May 2024 in a tertiary hospital. Collected variables: age, BMI, serum levels, FCP and CRP at 0, 6, 12, and 24 months from baseline, persistence, clinical response and remission at 6, 12, and 24 months. Efficacy was evaluated at week 26±6, 52±6 and 104±6 according to clinical history data. Clinical remission (Crem) was defined as obtaining a Harvey-Bradshaw index (HBI) &lt;5. Clinical response (CResp): reduction of &gt;3 points in HBI with respect to baseline. Normalisation of inflammatory biomarkers: CRP &lt;5 mcg/mL and FCP &lt;250 mcg/mL. Serum UTK levels were measured by ELISA techniques. <h3>Results</h3> 89 patients and 232 ustekinumab level determinations were recorded. Median age (IQR) was 44.5 (30.5–54) and 46,1% were female (table 1). Detectable levels of anti-drug antibodies were found in only one patient, but with a low titre. At week 52, 80.8% (n=59) of patients had CResp, 50.7% (n=37) had CRem. Median ustekinumab trough concentration was higher in responders (3.74 (1.6–5.8) μg/mL) than non-responders (2.54 (0.7–8.1) μg/mL; p=0.84); also in patients in CRem but no significant difference was found (p=0.87). At 24 months, 90.2% (n=37) had a CResp, 34.1% (n=14) CRem. Median trough concentration showed no differences between patients with CResp (7.49 (4.2–12.5) μg/mL) and those without (6.22 (3.9–9.0) μg/mL;p= 0.780), and also for CRem (p=0057). CPF showed a median reduction of 30% (0.05–83%) at 6 months, and 41% (17–80%) at 12 months, achieving 63.4% of patients normalisation of biochemical parameters at 12 months. The roc curve analysis shows a moderate specificity and sensitivity of levels and CResp at 24 months with an AUC=0.64. Cut-off point predicting long-term response in our sample was 2.2μg/mL. <h3>Conclusion and Relevance</h3> Higher trough concentrations seem to be associated with greater clinical response. A larger cohort, with extended follow-up and more diverse patient populations, will be needed to test the robustness of the results. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest