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

Authors

• 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.

APA Citation

Adler, Jeremy; Galanko, Joseph A.; Ammoury, Rana; Benkov, Keith J.; Bousvaros, Athos; Boyle, Brendan; Cabrera, José M.; Chun, Kelly Y.; Dorsey, Jill; Ebach, Dawn R.; Firestine, Ann M.; Gulati, Ajay S.; Herfarth, Hans H.; Jester, Traci W.; Kaplan, Jess L.; Leibowitz, Ian; Linville, Tiffany M.; Margolis, Peter A.; Minar, Phillip; Molle-Rios, Zarela; Moses, Jonathan; Olano, Kelly; Pashankar, Dinesh S.; Pitch, Lisa; Saeed, Shehzad A.; Samson, Charles M.; Sandberg, Kelly; Steiner, Steven J.; Strople, Jennifer A.; Sullivan, Jillian S.; Wali, Prateek D.; and Kappelman, Michael D., "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" (2024). GW Authored Works. Paper 5813.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5813

Department

Pediatrics