TOPLINE:

Ustekinumab concentrations at week 8 of treatment were associated with better endoscopic outcomes in patients with inflammatory bowel disease (IBD) at week 24, with concentrations above 4.5 μg/mL predicting endoscopic remission.

METHODOLOGY:

• Researchers conducted this prospective observational study at a hospital in Barcelona from June 2022 to September 2023 to examine the relationship between serum concentrations of ustekinumab and clinical, biochemical, and endoscopic outcomes.
• A total of 70 adult patients with moderate-to-severe Crohn's disease or ulcerative colitis (median age, 46 years; 51.4% women) were included.
• Participants received weight-adjusted intravenous ustekinumab, followed by maintenance therapy of subcutaneous ustekinumab every 4 or 8 weeks or intravenous ustekinumab every 4 weeks.
• All patients underwent endoscopic examination. Data regarding biochemical marker assessment and trough concentrations of ustekinumab were collected at baseline and at weeks 8, 16, and 24.
• The primary outcome was endoscopic remission, defined as a simple endoscopic score for Crohn's disease ≤ 2 and a Mayo endoscopic score of 0 for ulcerative colitis, at week 24. Secondary endpoints included clinical response and endoscopic improvement.

TAKEAWAY:

• Patients who achieved endoscopic remission and response at week 24 had higher ustekinumab concentrations at week 8 than those who did not (4.5 vs 2.6 μg/mL for remission; P = .0028 and 4.1 vs 2.4 μg/mL for response; P = .0024).
• Patients with ustekinumab concentrations in the highest quartile at week 8 (> 4.5 μg/mL) had higher rates of endoscopic remission at week 24 (66.7% in quartile 4 vs 20% in quartile 1, 33.3% in quartile 2, and 28.6% in quartile 3; P = .012).
• A ustekinumab concentration threshold of 4.5 μg/mL at week 8 predicted endoscopic remission at week 24, with a sensitivity of 54.5% and a specificity of 83.8%, and a threshold of 3.5 μg/mL predicted endoscopic response at week 24, with a sensitivity of 53.8% and a specificity of 87%.
• Patients with longer disease duration faced a higher risk of stopping ustekinumab therapy (adjusted odds ratio, 1.034; P = .035). Patients with ustekinumab concentrations in the highest quartile at week 8 (> 4.5 μg/mL) did not have better drug persistence rates than others.

IN PRACTICE:

"[The study authors] confirm an exposure–response relationship between UST [ustekinumab] concentrations and endoscopic outcomes in IBD, with week 8 levels serving as an early predictor of treatment success. These findings support the potential role of proactive TDM [therapeutic drug monitoring] to guide treatment optimization," the authors wrote.

SOURCE:

This study was led by Xavier Serra-Ruiz, Hospital Universitari Vall d'Hebron, Passeig de la Vall d'Hebron, Barcelona, Spain. It was published online on October 05, 2025, in Therapeutic Advances in Gastroenterology.

LIMITATIONS:

This study was limited by its single‑centre design and the modest sample size, and the absence of ustekinumab concentration measurements before week 8 prevented the assessment of very early drug concentrations as potential predictors.

DISCLOSURES:

This study did not receive any specific funding. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.