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

Frontiers in Pharmacology

Pharmacology

Paola Mian¹  Patrick F. van Rheenen²  Marleen Bouhuys² 

[1] Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, Groningen, Netherlands;Department of Pediatric Gastroenterology, Hepatology and Nutrition, Beatrix Children’s Hospital, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands;

关键词: ustekinumab;    therapeutic drug monitoring;    Crohn’s disease;    inflammatory bowel disease;    pediatrics;   

DOI  :  10.3389/fphar.2023.1180750

 received in 2023-03-06, accepted in 2023-09-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Bouhuys, Mian and van Rheenen.