P794 Relationship between Ustekinumab Trough Concentrations and Clinical, Biochemical and Endoscopic Outcomes in Crohn’s Disease; A Multi-Center Nationwide Study (TARGET STUDY)

Abstract Background Ustekinumab (UST) has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn’s disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real life settings Methods We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6mg/kg intravenous induction followed by 90 mg every 4 or 8 weeks during maintenance were included. Clinical, biochemical, and endoscopic outcomes, trough concentrations of ustekinumab that was taken from week 42 to week 52 were included. Primary outcome was to assess if ustekinumab trough concentrations were associated with clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes Results A total of 137 patients with CD. mean age of 34.1 years and 83 (60.6%) males. The mean serum levels of ustekinumab was 7.2 (SD 4.5). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and SES-CD score (r = -0.464, p < 0.001. Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by HBI score (r = -0.582, p < 0.001), C-Reactive Protein(CRP) levels (r = -0.598, p < 0.001) and fecal calprotectin (FCAL) levels (r = -0.529, p < 0.001). A multivariate analysis adjusted for age, sex and BMI showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/ml was associated with 24% increase in the likelihood of having an SES-CD score less than 3 (OR 1.24, CI 1.12-1.37, P<0.001), 44% more likely to achieve HBI score less than 5 (OR 1.44, CI 1.26-1.65, P<0.001), 52% higher likelihood of CRP less than 10 (OR 1.52, CI 1.31-1.77, p < 0.001), and 42% increased likelihood of FCAL less than 250 (OR 1.42, CI 1.24-1.62, p < 0.001). Conclusion Ustekinumab trough concentrations above 4.5 mcg/ml was associated with clinical, biochemical and endoscopic remission in Crohn’s disease. Prospective data is warranted to confirm these findings