Predictive models assessing the response to ustekinumab highlight the value of therapeutic drug monitoring in Crohn’s disease

Ustekinumab trough levels in children with Crohn’s disease refractory to anti-tumor necrosis factor agents: a prospective case series of off-label use

“…Establishing an exposure–response relationship is the first step in developing a TDM strategy. Multiple studies have demonstrated such a relationship of ustekinumab in adult CD patients ( Battat et al, 2017 ; Adedokun et al, 2018 ; Verstockt et al, 2019 ; Painchart et al, 2020 ; Thomann et al, 2020 ; Gómez Espín et al, 2021 ; Yao et al, 2021 ; Hirayama et al, 2022 ; Liefferinckx et al, 2022 ), and our report additionally could support an exposure–response relationship in children. Next, target trough levels must be determined.…”

“…In the absence of specific target trough levels for children, adult targets were often used. For ustekinumab, a variety of target trough levels have been appointed in adults, partly depending on the timing of measurement and the outcome of interest ( Battat et al, 2017 ; Adedokun et al, 2018 ; Verstockt et al, 2019 ; Painchart et al, 2020 ; Thomann et al, 2020 ; Gómez Espín et al, 2021 ; Yao et al, 2021 ; Hirayama et al, 2022 ; Liefferinckx et al, 2022 ). An overview of these target ustekinumab trough levels and therapeutic outcomes in adult patients with CD is presented in table 3 .…”

“…During maintenance (i.e., ≥16 weeks after induction), target trough levels >0.8–1.4 μg/mL are associated with clinical remission ( Adedokun et al, 2018 ; Gómez Espín et al, 2021 ). Ustekinumab trough levels ≥4.5 are associated with biochemical response ( Battat et al, 2017 ), trough levels >1.7–2.0 with biochemical remission, ( Gómez Espín et al, 2021 ; Hirayama et al, 2022 ), >1.6–4.5 with endoscopic response ( Battat et al, 2017 ; Verstockt et al, 2019 ; Liefferinckx et al, 2022 ), and trough levels >1.12–2.0 with endoscopic remission ( Yao et al, 2021 ; Hirayama et al, 2022 ). This is consistent with the trough levels found in case 2 of our series, who is in clinical remission on standard dosing.…”

“…TDM has been proven to increase the efficacy and decrease the toxicity of anti-TNF therapy ( Kapoor and Crowley, 2021 ). Studies on adults suggest that ustekinumab may be suitable for TDM, based on an extensive inter- and intraindividual variability in pharmacokinetics and the presence of an exposure–response relationship ( Vande Casteele et al, 2017 ; Adedokun et al, 2018 ; Gómez Espín et al, 2021 ; Alsoud et al, 2022 ; Liefferinckx et al, 2022 ; Proietti et al, 2022 ). Development of anti-ustekinumab antibodies is uncommon ( Bots et al, 2021 ).…”

Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease

“…Available data on the correlation between trough serum ustekinumab drug concentrations and clinical outcomes have been mixed, making the role of therapeutic drug monitoring less clear. Multiple studies, though, have shown an association between higher drug levels and better clinical and biochemical response to ustekinumab [15,[44][45][46][47]. The majority of these studies evaluated serum trough levels via ELISA at the time of ustekinumab induction or mobility shift assay and at follow-up periods up to week 26.…”