Higher-Dose Infliximab Induction Achieves Better Maintenance Trough Levels in a National Pediatric IBD Cohort-A...

Area of Science:

• Pediatric Gastroenterology
• Pharmacology
• Immunology

Background:

• Previous studies indicated 5 mg/kg infliximab (IFX) dosing was linked to inadequate trough levels (TLs) in pediatric inflammatory bowel disease (IBD).
• An empiric shift to 10 mg/kg IFX dosing was implemented in 2019 for proactive drug monitoring.

Purpose of the Study:

• To retrospectively evaluate the efficacy of 5 mg/kg versus 10 mg/kg IFX induction dosing in pediatric IBD patients.
• To determine the proportion of patients achieving target pre-fourth TLs (≥5 µg/mL) with each dosing regimen.

Main Methods:

• Retrospective analysis of 122 pediatric IBD patients initiated on 5 mg/kg or 10 mg/kg IFX between 2018 and 2020.
• Primary outcome: pre-fourth TL ≥5 µg/mL. Secondary outcomes included pre-third TLs, treatment escalation/de-escalation, and IFX exposure.

Main Results:

• The 10 mg/kg group showed significantly higher rates of achieving pre-fourth TLs (56% vs 12.5%, P<.001) and target pre-third TLs (80% vs 6%, P<.001) compared to the 5 mg/kg group.
• Patients on 5 mg/kg IFX were more likely to require treatment escalation (78% vs 45%, P<.001) and less likely to de-escalate therapy (10% vs 29%, P=.008).
• Despite dose differences, IFX exposure per kg/week, durability, and clinical outcomes were similar by one year, suggesting TDM's role.

Conclusions:

• Empiric 5 mg/kg IFX induction is inadequate for achieving target TLs in the majority of pediatric IBD patients, particularly Crohn's disease.
• Higher infliximab induction doses should be considered for pediatric IBD, especially when proactive therapeutic drug monitoring is not consistently available.
• Real-world data supports the need for dose optimization in pediatric IBD to ensure therapeutic efficacy.