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

• Main Authors: Marleen Bouhuys (Author), Paola Mian (Author), Patrick F. van Rheenen (Author)
• Format: Book
• Published: Frontiers Media S.A., 2023-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Background: Ustekinumab is used off-label in pediatric Crohn's disease refractory to anti-tumor necrosis factor. Data on optimal dosing, target trough levels, and potential benefit of therapeutic drug monitoring in children treated with ustekinumab are limited.Materials and Methods: We describe a series of six adolescents who consented to be treated with ustekinumab. We measured their trough levels, C-reactive protein, and fecal calprotectin before every administration.Results: Standard adult dosing was effective to achieve biochemical remission (fecal calprotectin < 250 mg/kg) in one patient and clinical remission (resolution of symptoms) in another. The other four patients failed to respond on standard dosing and underwent intravenous re-induction 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.Conclusion: In this report, we show that ustekinumab can induce remission in pediatric patients with anti-tumor necrosis factor refractory Crohn's disease. 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 therapeutic drug monitoring strategies, and, if applicable, optimal target trough levels.

Item Description

1663-9812
10.3389/fphar.2023.1180750