"HLA DQA1*05 and risk of anti-TNF treatment failure and anti-drug antib" by Jeremy Adler, Joseph A. Galanko et al.
 

HLA DQA1*05 and risk of anti-TNF treatment failure and anti-drug antibody development in children with Crohn's Disease: HLA DQA1*05 and Pediatric Crohn's Disease

Jeremy Adler, Division of Pediatric Gastroenterology, C.S. Mott's Children's Hospital, Michigan Medicine, University of Michigan, Ann Arbor, MI.
Joseph A. Galanko, Department of Pediatrics, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Rana Ammoury, Department of Pediatrics, Children's Hospital of the King's Daughters, Norfolk, Virginia.
Keith J. Benkov, Icahn School of Medicine at Mount Sinai, New York, NY.
Athos Bousvaros, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA.
Brendan Boyle, Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, OH.
José M. Cabrera, Medical College of Wisconsin, Milwaukee, WI.
Kelly Y. Chun, LabCorp Diagnostics, Burlington, NC.
Jill Dorsey, Nemours Children's Health, Jacksonville, Florida.
Dawn R. Ebach, Division of Pediatric Gastroenterology, University of Iowa, Iowa City, IA.
Ann M. Firestine, Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Ajay S. Gulati, Department of Pediatrics, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Hans H. Herfarth, Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC.
Traci W. Jester, Division of Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL.
Jess L. Kaplan, Division of Pediatric Gastroenterology, Mass General for Children, Harvard Medical School, Boston, MA.
Ian Leibowitz, George Washington University School of Medicine, Children's National Medical Center, Washington DC.
Tiffany M. Linville, Atrium Health Levine Children's Hospital, Charlotte, NC.
Peter A. Margolis, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
Phillip Minar, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
Zarela Molle-Rios, Nemours Children's Health, Wilmington.
Jonathan Moses, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH Rainbow Babies and Children's Hospital, Cleveland, OH.
Kelly Olano, Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Dinesh S. Pashankar, Department of Pediatrics (Gastroenterology), Yale University School of Medicine, New Haven, CT.
Lisa Pitch, ImproveCareNow Inc., Essex Junction, VT.
Shehzad A. Saeed, Department of Gastroenterology, Dayton Children's Hospital, Boonshoft School of Medicine, Wright State University, Dayton, Ohio.
Charles M. Samson, Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
Kelly Sandberg, Department of Gastroenterology, Dayton Children's Hospital, Boonshoft School of Medicine, Wright State University, Dayton, Ohio.
Steven J. Steiner, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.
Jennifer A. Strople, Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Pediatrics, Northwestern Feinberg School of Medicine, Chicago, IL.
Jillian S. Sullivan, Larner College of Medicine at the University of Vermont Burlington, VT.
Prateek D. Wali, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, State University of New York, Upstate Medical University, Syracuse, New York.
Michael D. Kappelman, Department of Pediatrics, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Document Type

Journal Article

Publication Date

10-18-2024

Journal

The American journal of gastroenterology

DOI

10.14309/ajg.0000000000003135

Abstract

OBJECTIVES: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data. METHODS: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs. combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development. RESULTS: A trend towards increased treatment failure among HLA DQA1*05 positive participants was not significant (HR 1.58, 95% CI 0.95-2.62; p=0.08). After stratification by HLA DQA1*05 and by methotrexate vs. placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05 positive patients on placebo (HR 0.31, 95% CI 0.13-0.70; p=0.005).A trend toward increased ADA development among HLA DQA1*05 positive participants was not significant (odds ratio [OR] 1.96, 95% CI 0.90-4.31, p=0.09). After further stratification, HLA DQA1*05 negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05 positive patients on placebo (OR 0.12, 95% CI 0.03-0.55; p=0.008). CONCLUSIONS: In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

Department

Pediatrics

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