Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab

Objective

Therapeutic drug monitoring is used clinically to guide anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD), but its use for ustekinumab (UST) remains unclear. This study aimed to determine predictive variables of UST levels.

Methods

In this retrospective cohort of patients with IBD, UST trough levels were drawn at maintenance dosing. Relationships between UST trough levels and demographics, therapy, and outcomes were analyzed. Machine-learning models were used to infer combinatorial traits predictive of UST levels.

Results

Altogether 177 patients with IBD on UST had a mean UST trough level of 4.742 μg/mL. The injection schedule correlated significantly (P < 0.001) with UST levels. Naiveté to anti-TNFs correlated with higher UST levels (P = 0.048). Univariate analysis revealed that higher inflammatory biomarkers significantly correlated to lower UST levels and a lower Simple Endoscopic Score to Crohn's Disease to adequate UST levels (P = 0.018). Multivariate analysis identified body mass index (BMI), previous anti-TNF failure, and laboratory flare as predictors of UST levels with an area under the receiver operating characteristic curve (AUROC) of 0.72. The UST cut-off level of 5.77 μg/mL yielded a 0.79 AUROC, 80% sensitivity, and 81% specificity for predicting endoscopic remission of Crohn's disease. For the clinical remission end-point in ulcerative colitis, UST level of 4.73 μg/mL yielded a 0.69 AUROC, 53% sensitivity, and 86% specificity.

Conclusions

Higher UST levels correlated with less disease activity. BMI was an important consideration for UST response as well. Therefore, UST dose adjustments to reach target levels may optimize response.