Ustekinumab concentrations and outcomes

Ustekinumab (UST) is a monoclonal antibody targeting the p40 subunit of interleukin-12/23. Evidence suggests a relationship between UST concentrations and therapeutic outcomes. This study aimed to evaluate the association between UST trough concentrations during the induction phase and clinical and especially endoscopic outcomes at week 24 in patients with Crohn’s disease (CD) and ulcerative colitis (UC).
Methods
Patients with CD and UC were included from the start of UST treatment. Intensification and maintenance regimens were based on standard clinical practice. The primary objective was to assess endoscopic remission at week 24, defined as a simple-endoscopic-score (SES-CD) ≤2 for CD and a Mayo endoscopic score (MES) ≤1 for UC. Quartile analysis and logistic regression assessed the relationship between UST concentrations and endoscopic outcomes, while logistic and Cox proportional hazards regressions identified variables associated with endoscopic remission and treatment discontinuation, respectively.
Results
Seventy patients (45 with CD) were enrolled. Those achieving endoscopic response and remission at week 24 had higher UST levels at week 8 (4.0 μg/mL vs. 2.5 μg/mL, p=0.002; 3.9 μg/mL vs. 2.9 μg/mL, p=0.047). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (> 4.5 μg/mL) had higher rates of endoscopic remission (69% [Q4] vs. 23% [Q1], p=0.014; 24% [Q2], p=0.003; 31% [Q3], p=0.024). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC=0.678, sensitivity 52.5%, specificity 84.6%), while 3.5 μg/mL predicted endoscopic response (AUC=0.732, sensitivity 63.6 %, specificity 73.1 %). Logistic regression did not reveal other predictive factors for response. Longer disease duration correlated with a higher risk of UST discontinuation (OR 1.034, 95% CI 1.002-1.068, p=0.035). Higher UST concentrations in Q4 did not result in greater drug persistence (p=0.319).
Conclusion
UST concentrations at week 8 were positively associated with endoscopic outcomes at week 24, with a threshold of 4.5 μg/mL reliably predicting endoscopic remission. Further randomized clinical trials are warranted to explore whether optimizing UST treatment based on post-induction concentrations can enhance therapeutic outcomes.