Inflamm Bowel Dis. 2024 Oct 3;30(10):1678-1685.doi: 10.1093/ibd/izad307.

Ruben J Colman ^1 2 3, Stephanie A Vuijk ⁴, Ron A A Mathôt ⁵, Johan Van Limbergen ^6 7, Maria M E Jongsma ⁴, Marco W J Schreurs ⁸, Phillip Minar ^3 9, Lissy de Ridder ⁴, Geert R A M D'Haens ²

Author information

¹Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.

²Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands.

³Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

⁴Department of Pediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.

⁵Department of Hospital Pharmacy & Clinical Pharmacology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands.

⁶Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands.

⁷Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, University of Amsterdam, Amsterdam, the Netherlands.

⁸Department of Immunology, Erasmus MC, Rotterdam, the Netherlands.

⁹Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Abstract

Background: The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD).

Methods: This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5.

Results: This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5.

Conclusions: This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX.