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

Dawn R Ebach; Traci W Jester; Joseph A Galanko; Ann M Firestine; Rana Ammoury; Jose Cabrera; Julie Bass; Phillip Minar; Kelly Olano; Peter Margolis; Kelly Sandberg; Tiffany M Linnville; Jess Kaplan; Lisa Pitch; Steven J Steiner; Dorsey Bass; Jonathan Moses; Jeremy Adler; Ajay S Gulati; Prateek Wali; Dinesh Pashankar; Anastasia Ivanova; Hans Herfarth; David A Wohl; Keith J Benkov; Jennifer Strople; Jillian Sullivan; Jeanne Tung; Zorela Molle-Rios; Shehzad A Saeed; Athos Bousvaros; Michael D Kappelman

doi:10.14309/ajg.0000000000002741

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

Am J Gastroenterol. 2024 Mar 28. doi: 10.14309/ajg.0000000000002741. Online ahead of print.

Authors

Dawn R Ebach¹, Traci W Jester², Joseph A Galanko³, Ann M Firestine³, Rana Ammoury⁴, Jose Cabrera⁵, Julie Bass⁶, Phillip Minar⁷, Kelly Olano⁷, Peter Margolis⁷, Kelly Sandberg⁸, Tiffany M Linnville⁹, Jess Kaplan¹⁰, Lisa Pitch¹¹, Steven J Steiner¹², Dorsey Bass¹³, Jonathan Moses¹³, Jeremy Adler¹⁴, Ajay S Gulati³, Prateek Wali¹⁵, Dinesh Pashankar¹⁶, Anastasia Ivanova¹⁷, Hans Herfarth¹⁸, David A Wohl¹⁹, Keith J Benkov²⁰, Jennifer Strople²¹, Jillian Sullivan²², Jeanne Tung²³, Zorela Molle-Rios²⁴, Shehzad A Saeed⁸, Athos Bousvaros²⁵, Michael D Kappelman³

Affiliations

¹ Division of Gastroenterology, Hepatology, Pancreatology, and Nutrition, University of Iowa, Iowa City, Iowa, USA.
² Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
³ Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁴ Department of Pediatrics, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.
⁵ Department of Pediatrics, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
⁶ Department of Pediatrics, Children's Mercy Medical Center, UMKC School of Medicine, Kansas City, Missouri, USA.
⁷ Department of Pediatrics, Cincinnati Children's Medical Center, Cincinnati, Ohio, USA.
⁸ Boonshoft School of Medicine, Wright State University and Department of Medical Affairs, Dayton Children's Hospital, Dayton, Ohio, USA.
⁹ Department of Pediatrics, Atrium Health Levine Children's Hospital, Charlotte, North Carolina, USA.
¹⁰ Division of Pediatric Gastroenterology, Mass General Hospital for Children, Boston, Massachusetts, USA.
¹¹ ImproveCareNow Parent Representative.
¹² Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹³ Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford Medicine Children's Health, Palo Alto, California, USA.
¹⁴ Department of Pediatrics, University of Michigan-C.S. Mott Children's Hospital, Ann Arbor, Michigan, USA.
¹⁵ Karjoo Family Center for Pediatric Gastroenterology, Hepatology, and Nutrition, Upstate Golisano Children's Hospital, SUNY Upstate Medical Center, Syracuse, New York, USA.
¹⁶ Pediatric Gastroenterology and Hepatology, Yale New Haven Children's Hospital, Yale School of Medicine, New Haven, Connecticut, USA.
¹⁷ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁸ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁹ University of North Carolina Institute of Global Health and Infectious Diseases, Chapel Hill, North Carolina, USA.
²⁰ Division of Pediatric Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
²¹ Division of Pediatric Gastroenterology, Ann & Robert Lurie Children's Hospital, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA.
²² Children's Hospital of Vermont, University of Vermont, Burlington, Vermont, USA.
²³ Oklahoma Children's Hospital, University of Oklahoma, Oklahoma City, Oklahoma, USA.
²⁴ Nemour Children's Health, Wilmington, Delaware, USA.
²⁵ Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.

PMID: 38445644
DOI: 10.14309/ajg.0000000000002741

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.

Abstract

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