Higher ustekinumab concentrations in induction are associated with better endoscopic outcomes in inflammatory bowel disease.

Abstract

Background: Evidence suggests a relationship between ustekinumab (UST) concentrations and therapeutic outcomes in inflammatory bowel disease.

Objectives: This study aimed to evaluate the association between UST concentrations during the induction phase and treatment outcomes at week 24 in patients with Crohn's disease (CD) and ulcerative colitis (UC). The primary outcome was endoscopic remission at week 24, defined as a simple endoscopic score (SES-CD) ⩽2 for CD and a Mayo endoscopic score = 0 for UC. Secondary outcomes included endoscopic response, clinical remission, and treatment persistence.

Design: This was a prospective observational study assessing clinical and endoscopic outcomes in CD and UC patients starting UST therapy.

Methods: Consecutive patients with CD and UC were included at the initiation of UST treatment. Trough UST concentrations were measured at weeks 8, 16, and 24 after the first intravenous dose, and the main outcomes were assessed at week 24. Endoscopic and clinical parameters were used to evaluate treatment efficacy and persistence.

Results: Seventy patients (45 with CD) were enrolled. Those achieving endoscopic remission and response at week 24 had higher UST levels at week 8 (4.5 vs 2.6 μg/mL, p = 0.0028; 4.1 vs 2.4 μg/mL, p = 0.0024, respectively). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (>4.5 μg/mL) had higher rates of endoscopic remission (66.7% (Q4) vs 20% (Q1); 33.3% (Q2); 28.6% (Q3); p = 0.012). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC = 0.7, sensitivity 54.5%, specificity 83.8%), while 3.5 μg/mL predicted endoscopic response (AUC = 0.732, sensitivity 53.8%, specificity 87%). Longer disease duration correlated with a higher risk of UST discontinuation (odds ratio, 1.034, 95% confidence interval, 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.