Ustekinumab trough levels associated with remission in 76 adults in single-center Crohn’s study

In a cross-sectional study of 76 adults with Crohn’s disease receiving maintenance ustekinumab at a Baghdad hospital, 43 of 55 patients whose trough concentration reached at least 1 μg/mL were in clinical remission, compared with 6 of 21 patients below that threshold. The investigators reported an association between higher ustekinumab exposure and remission, although the single-center convenience sample and modest number of participants limit the findings’ generalizability.

The study was conducted from January to June 2026 at the Gastroenterology and Hepatology Teaching Hospital/Medical City in Baghdad. The hospital treats patients from across Iraq, but the study did not recruit a population-based sample from every governorate. Eligible participants were adults with documented Crohn’s disease who attended the center during the study period and provided informed consent. The researchers used convenience sampling and excluded patients with several other immune conditions, recent steroid use, cancer, specified Crohn’s disease complications, or insufficient monitoring data.

All participants received intravenous induction ustekinumab at week 0, using a weight-based dose of 260 mg for patients below 55 kg, 390 mg for those weighing 55–85 kg, and 520 mg for those above 85 kg. Maintenance treatment consisted of 90 mg administered subcutaneously every eight weeks, beginning eight weeks after induction. Participants had completed at least 24 weeks of continuous treatment before enrollment, allowing assessment during maintenance therapy at what the investigators described as pharmacokinetic steady state.

Each patient was sampled once, immediately before a scheduled maintenance dose and at the end of the eight-week dosing interval. The same visit provided a concurrent measurement of disease activity using the Crohn’s Disease Activity Index. Remission was defined as a score below 150, while a score of 150 or higher indicated active disease. Blood samples were used to quantify the ustekinumab trough level, assess anti-drug antibodies, and measure laboratory and inflammatory markers.

The study grouped patients according to whether they met a 1 μg/mL trough threshold derived from earlier literature. Among the 55 patients who reached the threshold, the median ustekinumab concentration was 1.50 μg/mL, with an interquartile range of 1.25–1.73 μg/mL. Among the 21 who did not reach it, the median was 0.70 μg/mL, with an interquartile range of 0.56–0.87 μg/mL; the difference was significant at p<0.001. Only one patient was positive for anti-ustekinumab antibodies, and the difference in antibody positivity between the concentration groups was not statistically significant.

Unadjusted binary logistic regression estimated that each additional 1 μg/mL of trough concentration was associated with 9.35 times the odds of clinical remission, with a 95% confidence interval of 2.61–33.33 and p=0.001. After adjustment for concomitant azathioprine use and ustekinumab treatment duration, the reported adjusted odds ratio was 14.30, with a 95% confidence interval of 3.35–58.80 and p<0.001. These estimates came from the same observational dataset, and the study did not report a statistical comparison between the unadjusted and adjusted coefficients. The results therefore describe an association rather than establishing that increasing ustekinumab exposure would cause remission.

Patients at or above the target concentration also had lower inflammatory markers and higher serum albumin. Median C-reactive protein was 1.90 mg/L in the target-level group and 22.00 mg/L in the lower-concentration group. Median erythrocyte sedimentation rates were 24 and 64 mm/hr, respectively, while median serum albumin was 41.60 and 35.00 g/L. All three comparisons were significant at p<0.001. The analysis did not determine whether lower inflammation contributed to higher drug concentrations, higher concentrations were associated with lower inflammation, or other factors influenced both measures.

The investigators classified the patients’ treatment-response patterns using concentration, antibody status, and disease activity. Among 55 patients at the target level, 43 were in remission and 12 had active disease; the latter pattern was categorized as mechanistic treatment failure. Among the 21 patients below the target, six were in remission, 14 had active disease with negative anti-drug antibodies, and one had active disease with positive antibodies. The authors classified the antibody-negative cases as non-immune pharmacokinetic failure and the antibody-positive case as immune pharmacokinetic failure. These classifications were the basis of the study’s proposed management options, rather than outcomes tested in an intervention trial.

The findings add an Iraqi clinical cohort to earlier evidence that the investigators described as inconsistent. They cited a Spanish real-world cohort in which trough levels were associated with clinical response, while studies from the Netherlands and Italy reported no association. The authors cited differences in remission definitions, laboratory assays, treatment phase, and dosing intervals as possible explanations. This study used a uniform eight-week maintenance schedule and measured drug exposure and disease activity concurrently, but it was not designed to resolve those differences comparatively.

Important limitations include the modest single-center sample, convenience sampling, and restriction to patients who attended the Baghdad center during the six-month enrollment period. These features may limit statistical power, introduce selection bias, and restrict external validity. Samples were also stored for up to five months before laboratory analysis, which delayed the availability of treatment advice. The authors stated that larger multicenter research is needed to confirm the results and clarify the role of therapeutic drug monitoring in patients with Crohn’s disease receiving ustekinumab.

Subject of Research: Association between maintenance ustekinumab trough concentrations and clinical remission in adults with Crohn’s disease

Article Title: Therapeutic drug monitoring of ustekinumab in Crohn’s disease patients: a real-world study

Article References: Jebur, N. J., Jabbar Kadhim, D., & Al Issa, I. H. (2026). Therapeutic drug monitoring of ustekinumab in Crohn’s disease patients: a real-world study. Pharmacia, 73, Article e211586. https://doi.org/10.3897/pharmacia.73.e211586

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e211586

Keywords: Crohn’s disease, ustekinumab, therapeutic drug monitoring, trough concentration, clinical remission, anti-drug antibodies, inflammatory markers, cross-sectional study, real-world evidence, Therapeutic, drug, monitoring