J Pediatr Gastroenterol Nutr. 2024 Jul;79(1):62-75.doi: 10.1002/jpn3.12221. Epub 2024 May 2.

Dwight A Winter ¹, Pauline de Bruyne ², Janneke van der Woude ³, Dimitris Rizopoulos ⁴, Lissy de Ridder ¹, Janneke Samsom ⁵, Johanna C Escher ¹

Author information

¹Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands.

²Department of Pediatrics, Ghent University Hospital, Ghent University, Ghent, Belgium.

³Department of Gastroenterology, Erasmus MC, Rotterdam, Netherlands.

⁴Department of Biostatistics, Erasmus MC, Rotterdam, Netherlands.

⁵Laboratory of Paediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands.

Abstract

Objectives: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients.

Methods: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD.

Results: During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response.

Conclusion: Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD.