Toward personalized therapeutic drug monitoring of ustekinumab in Crohn’s disease: influence of previous exposure to biologics

Background: Unlike infliximab, ustekinumab (UST) has shown inconsistent associations between drug concentration and clinical efficacy across studies, with varying cutoff therapeutic trough levels (TLs) proposed. Objectives: Given that patients have different histories of biologic use, we aimed to evaluate whether therapeutic TLs of ustekinumab require optimization in patients with Crohn’s disease. Design: Cohort study. Methods: To assess whether ustekinumab has a potential therapeutic cutoff value, we evaluated and compared its 1-year TLs in 14 biologic-naïve patients and in 26 patients who were prescribed the drug after experiencing a loss of response to previous biologic therapies. Results: The mean TL in the biologic-naïve patients was 3.41 µg/mL, which was significantly higher than that in the biologic-experienced patients (1.46 µg/mL; p = 0.007). The duration of prior biologic therapy and disease activity correlated with the ustekinumab TLs. With regard to the optimal cutoff value for predicting deep remission at 1 year, the threshold was 2.34 µg/mL for the biologic-naïve patients (area under the receiver operating characteristic curve (AUC) = 0.909, p < 0.001) and 1.18 µg/mL for the biologic-experienced patients (AUC = 0.892, p < 0.001). Conclusion: Ustekinumab TLs in patients may differ according to their prior exposure to biologic agents and disease activity. Accordingly, rather than applying a uniform threshold, ustekinumab levels should be interpreted using individualized, patient-specific strategies in clinical practice.