Journal article
HLA DQA105 and risk of anti-TNF treatment failure and anti-drug antibody development in children with Crohn's Disease: HLA DQA105 and Pediatric Crohn's Disease
The American journal of gastroenterology, Vol.120(5), pp.1076-1086
05/2025
DOI: 10.14309/ajg.0000000000003135
PMID: 39423015
Abstract
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.OBJECTIVESHLA 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.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.METHODSWe 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.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).RESULTSA 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).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.CONCLUSIONSIn 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.
Details
- Title: Subtitle
- HLA DQA105 and risk of anti-TNF treatment failure and anti-drug antibody development in children with Crohn's Disease: HLA DQA105 and Pediatric Crohn's Disease
- Creators
- Jeremy Adler - University of MichiganJoseph A Galanko - University of North Carolina at Chapel HillRana Ammoury - Children's Hospital of The King's DaughtersKeith J Benkov - Icahn School of Medicine at Mount SinaiAthos Bousvaros - Boston Children's HospitalBrendan Boyle - Nationwide Children's HospitalJosé M Cabrera - Medical College of WisconsinKelly Y Chun - LabCorpJill DorseyDawn R Ebach - University of IowaAnn M Firestine - University of North Carolina at Chapel HillAjay S Gulati - University of North Carolina at Chapel HillHans H Herfarth - University of North Carolina at Chapel HillTraci W Jester - University of Alabama at BirminghamJess L Kaplan - Massachusetts General HospitalIan Leibowitz - Children's NationalTiffany M Linville - Levine Children's HospitalPeter A Margolis - University of CincinnatiPhillip Minar - University of CincinnatiZarela Molle-RiosJonathan Moses - Rainbow Babies & Children's HospitalKelly Olano - Cincinnati Children's Hospital Medical CenterDinesh S Pashankar - Yale UniversityLisa PitchShehzad A Saeed - Wright State UniversityCharles M Samson - Washington University in St. LouisKelly Sandberg - Wright State UniversitySteven J Steiner - Riley Hospital for ChildrenJennifer A Strople - Lurie Children's HospitalJillian S Sullivan - University of VermontPrateek D Wali - SUNY Upstate Medical UniversityMichael D Kappelman - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- The American journal of gastroenterology, Vol.120(5), pp.1076-1086
- DOI
- 10.14309/ajg.0000000000003135
- PMID
- 39423015
- NLM abbreviation
- Am J Gastroenterol
- ISSN
- 1572-0241
- eISSN
- 1572-0241
- Language
- English
- Electronic publication date
- 10/18/2024
- Date published
- 05/2025
- Academic Unit
- Stead Family Department of Pediatrics; Gastroenterology, Hepatology, Pancreatology, and Nutrition
- Record Identifier
- 9984736746602771
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