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Randomized Controlled Trial
. 2024 Jun 1;119(6):1110-1116.
doi: 10.14309/ajg.0000000000002741. Epub 2024 Mar 6.

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease

Dawn R Ebach  1 , Traci W Jester  2 , Joseph A Galanko  3 , Ann M Firestine  3 , Rana Ammoury  4 , Jose Cabrera  5 , Julie Bass  6 , Phillip Minar  7 , Kelly Olano  7 , Peter Margolis  7 , Kelly Sandberg  8 , Tiffany M Linnville  9 , Jess Kaplan  10 , Lisa Pitch  11 , Steven J Steiner  12 , Dorsey Bass  13 , Jonathan Moses  13 , Jeremy Adler  14 , Ajay S Gulati  3 , Prateek Wali  15 , Dinesh Pashankar  16 , Anastasia Ivanova  17 , Hans Herfarth  18 , David A Wohl  19 , Keith J Benkov  20 , Jennifer Strople  21 , Jillian Sullivan  22 , Jeanne Tung  23 , Zorela Molle-Rios  24 , Shehzad A Saeed  8 , Athos Bousvaros  25 , Michael D Kappelman  3
Affiliations
Randomized Controlled Trial

High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease

Dawn R Ebach et al. Am J Gastroenterol. .

Abstract

Introduction: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI).

Methods: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined.

Results: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 μg/mL, P = 0.02). IFX trough levels did not differ between BMI groups.

Discussion: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

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Conflict of interest statement

DRE has research support from Bristol Myers Squibb.

JB Pfizer Pediatric IBD Advisory Panel

PM has in-kind support from Janssen Scientific Affairs,LLC

JM speaker’s bureau for Abbvie and consulted with PCSI, Inc.

TML speaker’s bureau for Abbvie

SAS Advisory Board for Abbvie, Inc.

DP research support from Janssen and Abbvie

HH: Consulting for Alivio, AMAG, BMS, Boehringer, ExeGI, Finch, Fresenius Kabi, Galapagos, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres, Ventyx and research support from Artizan Biosciences , Allakos, NovoNordisk, and Pfizer.

AB has research support from Janssen, Abbvie, Takeda, Buhlman, Arena, Eli Lilly, Bristol Myers Squibb, and PROCISE Diagnostics. He has consulted for Takeda, Best Doctors, Eli Lilly, Fresensius Kabi, Alivio Therapeutics. Honoraria and Royalties from Up To Date and Boston University

MDK has consulted for Abbvie, Janssen, Pfizer, Takeda, and Lilly and is a shareholder in Johnson & Johnson

All others: none declared

Figures

Figure 1:
Figure 1:
Comparison of time to treatment failure among healthy weight and overweight/obese participants enrolled in the COMBINE clinical trial which randomized pediatric patients with Crohn’s disease initiating anti-TNF therapy to either combination therapy with low dose methotrexate or placebo. Panel A shows all participants, panel B shows infliximab initiators, and panel C shows adalimumab initiators.
Figure 2:
Figure 2:
Box and Whisker Plots Illustrating the Distribution of Infliximab and Adalimumab Levels Obtained 4 Months Following Enrollment among Overweight and Healthy Weight Children with Crohn’s Disease.
See this image and copyright information in PMC

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Publication types

Supplementary concepts