HLA for Predicting Risk of Anti-Drug Antibodies

Project start date and end date: 2021 - 2023


Developing antibodies to tumor necrosis factor α antagonist (anti-TNFα) medications commonly leads to loss of efficacy or allergic reactions. Preventing development of anti-drug antibodies is critically important to improving treatment efficacy and preventing loss of therapeutic options. Several strategies have been promoted to reduce risk of anti-drug antibodies, but there is little evidence for precision individualized approaches, and none in pediatrics. Human leukocyte antigen (HLA) DQ1*05 was recently found to be associated with increased incidence of developing antibodies to infliximab and adalimumab (Sazonovs A, Gastroenterol 2020;158:189-9). This study was groundbreaking, but it was limited to a homogeneous population of white adults with Crohn’s disease, and did not consider anti-TNFα dosing or trough levels.


The objective of this pediatric study is to assess predictors of developing anti-drug antibodies.

Research Topics & Methods:

Jeremy Adler, M.D., is co-investigator in a multicenter prospective randomized trial of anti-TNF monotherapy vs. concomitant therapy with methotrexate (combinetrial.org). From this study, we have stored serum, as well as detailed clinical and treatment information, from a cohort of 300 patients. The current study is an add-on study to assess predictors of anti-drug antibody development, including HLA-DQ1*05, clinical characteristics, and drug troughs.


If successful, this study will provide evidence for predicting patient risk of anti-drug antibody development. This will also serve as preliminary evidence for future funding to further investigate ways to individualize therapy to maximize efficacy and longevity.


This project is funded by the Gary and Rachel Glick Charitable Fund.

For more information, please contact:
Clinical Professor, Department of Pediatrics, Division of Pediatric Gastroenterology
Interim Director, Susan B. Meister Child Health Evaluation and Research Center
Director, Pediatric IBD Program
1500 E. Medical Center Drive
MPB D5200, Box SPC5718
Ann Arbor, MI 48109-5718