HLA for Predicting Risk of Anti-Drug Antibodies

Project start date and end date: 2021 - 2023

Background:

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.

Objectives:

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.

Implications:

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.

Funder:

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