High Body Mass Index and Response to Anti-TNF Therapy in Pediatric Crohn Disease.


Journal

The American journal of gastroenterology
ISSN: 1572-0241
Titre abrégé: Am J Gastroenterol
Pays: United States
ID NLM: 0421030

Informations de publication

Date de publication:
06 Mar 2024
Historique:
received: 21 12 2023
accepted: 14 02 2024
medline: 6 3 2024
pubmed: 6 3 2024
entrez: 6 3 2024
Statut: aheadofprint

Résumé

Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-TNF treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). The COMBINE trial compared anti-TNF monotherapy to combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI versus BMI Z score > 1, adjusting for prescribed anti-TNF (infliximab or adalimumab), trial treatment assignment (combination versus monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. Of 224 participants (162 infliximab initiators and 62 adalimumab initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among adalimumab initiators [7/10 (70%) vs 12/52 (23%), HR 0.29, p=.007] but not infliximab initiators. Additionally, adalimumab-treated patients with a high BMI had lower adalimumab levels compared to those with normal BMI (median 5.8 ug/mL vs 12.8 ug/mL, p=0.02). Infliximab trough levels did not differ between BMI groups. Overweight and obese patients with PCD are more likely to experience adalimumab treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard adalimumab dosing may be insufficient for overweight children with PCD. Among infliximab 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.

Sections du résumé

BACKGROUND BACKGROUND
Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-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 METHODS
The COMBINE trial compared anti-TNF monotherapy to combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI versus BMI Z score > 1, adjusting for prescribed anti-TNF (infliximab or adalimumab), trial treatment assignment (combination versus monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined.
RESULTS RESULTS
Of 224 participants (162 infliximab initiators and 62 adalimumab initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among adalimumab initiators [7/10 (70%) vs 12/52 (23%), HR 0.29, p=.007] but not infliximab initiators. Additionally, adalimumab-treated patients with a high BMI had lower adalimumab levels compared to those with normal BMI (median 5.8 ug/mL vs 12.8 ug/mL, p=0.02). Infliximab trough levels did not differ between BMI groups.
CONCLUSIONS CONCLUSIONS
Overweight and obese patients with PCD are more likely to experience adalimumab treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard adalimumab dosing may be insufficient for overweight children with PCD. Among infliximab 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.

Identifiants

pubmed: 38445644
doi: 10.14309/ajg.0000000000002741
pii: 00000434-990000000-01056
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Patient-Centered Outcomes Research Institute
ID : PCS-1406-18643
Pays : United States
Organisme : NIAMS NIH HHS
ID : U19ARD69525
Pays : United States

Informations de copyright

Copyright © 2024 by The American College of Gastroenterology.

Auteurs

Dawn R Ebach (DR)

Division of Gastroenterology, Hepatology, Pancreatology, and Nutrition, University of Iowa, Iowa City, Iowa, USA.

Traci W Jester (TW)

Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL.

Joseph A Galanko (JA)

Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Ann M Firestine (AM)

Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Rana Ammoury (R)

Department of Pediatrics, Children's Hospital of The King's Daughters, Norfolk, VA.

Jose Cabrera (J)

Department of Pediatrics, Children's Hospital of Wisconsin, Milwaukee, WI.

Julie Bass (J)

Department of Pediatrics, Children's Mercy Medical Center, UMKC School of Medicine, Kansas City, MO.

Phillip Minar (P)

Department of Pediatrics, Cincinnati Children's Medical Center, Cincinnati, OH.

Kelly Olano (K)

Department of Pediatrics, Cincinnati Children's Medical Center, Cincinnati, OH.

Peter Margolis (P)

Department of Pediatrics, Cincinnati Children's Medical Center, Cincinnati, OH.

Kelly Sandberg (K)

Boonshoft School of Medicine, Wright State University and Department of Medical Affairs, Dayton Children's Hospital, Dayton, OH.

Tiffany M Linnville (TM)

Department of Pediatrics, Atrium Health Levine Children's Hospital, Charlotte, NC.

Jess Kaplan (J)

Division of Pediatric Gastroenterology, Mass General Hospital for Children, Boston, MA, USA.

Lisa Pitch (L)

ImproveCareNow Parent Representative.

Steven J Steiner (SJ)

Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.

Dorsey Bass (D)

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford Medicine Children's Health, Palo Alto, CA.

Jonathan Moses (J)

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford Medicine Children's Health, Palo Alto, CA.

Jeremy Adler (J)

Department of Pediatrics, University of Michigan - C.S. Mott Children's Hospital, Ann Arbor, MI.

Ajay S Gulati (AS)

Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Prateek Wali (P)

Karjoo Family Center for Pediatric Gastroenterology, Hepatology, and Nutrition, Upstate Golisano Children's Hospital, SUNY Upstate Medical Center, Syracuse, NY.

Dinesh Pashankar (D)

Pediatric Gastroenterology and Hepatology, Yale New Haven Children's Hospital, Yale School of Medicine, New Haven, CT.

Anastasia Ivanova (A)

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Hans Herfarth (H)

Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

David A Wohl (DA)

University of North Carolina Institute of Global Health and Infectious Diseases, Chapel Hill, NC.

Keith J Benkov (KJ)

Division of Pediatric Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY.

Jennifer Strople (J)

Division of Pediatric Gastroenterology, Ann & Robert Lurie Children's Hospital, Northwestern Feinberg School of Medicine, Chicago, IL.

Jillian Sullivan (J)

Children's Hospital of Vermont, University of Vermont, Burlington, VT.

Jeanne Tung (J)

Oklahoma Children's Hospital, University of Oklahoma, Oklahoma City, OK.

Zorela Molle-Rios (Z)

Nemour Children's Health, Wilmington, DE.

Shehzad A Saeed (SA)

Boonshoft School of Medicine, Wright State University and Department of Medical Affairs, Dayton Children's Hospital, Dayton, OH.

Athos Bousvaros (A)

Department of Pediatrics, Boston Children's Hospital, Boston, MA.

Michael D Kappelman (MD)

Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Classifications MeSH