AUTHOR=Bouhuys Marleen , Mian Paola , van Rheenen Patrick F. 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1180750

DOI=10.3389/fphar.2023.1180750

ISSN=1663-9812

ABSTRACT=Background: Ustekinumab is used off-label in pediatric Crohn's disease (CD) refractory to antitumor necrosis factor (TNF). Data on optimal dosing, target trough levels and potential benefit of therapeutic drug monitoring (TDM) in children treated with ustekinumab is limited. Materials and Methods: We describe a series of six adolescents who consented to be treated with ustekinumab. We measured trough levels, C-reactive protein and fecal calprotectin (FC) before every administration. Results: Standard adult dosing was effective to achieve biochemical remission (FC<250 mg/kg) in one patient and clinical remission (resolution of symptoms) in a second. The other four patients failed to respond on standard dosing and underwent intravenous reinduction and interval shortening to increase ustekinumab trough levels. This resulted in biochemical remission in one patient and clinical remission in another, suggesting an exposure-response relationship. The remaining two patients had no therapeutic benefit and ustekinumab was discontinued.In this report we show that ustekinumab can induce remission in pediatric patients with anti-TNF refractory CD. It is worth escalating the dose before abandoning the drug as ineffective. Prospective studies in children are needed to determine long-term efficacy of ustekinumab, usefulness of TDM strategies and, if applicable, optimal target trough levels.