The genetic variant human leukocyte antigen (HLA)-DQA1*05, linked to the development of antidrug antibodies to antitumor necrosis factor (anti-TNF) therapies, appears in about 40% of people of European descent.

In an award-winning abstract (Outstanding Poster Presenter) at the American College of Gastroenterology (ACG) 2020 clinical meeting and postgraduate course, researchers from the University of Miami Miller School of Medicine sought to determine if this variant is also common among patients of Hispanic descent, and whether it is associated with antibody development to other biologics used in treating inflammatory bowel disease (IBD). Stephanie Ioannou, MD, presented the poster for her colleagues.

The research project included 714 adult patients who self-identified as Hispanic and provided consent for the institution’s IBD Biorepository, which identified 248 patients (34.7%) who carried the HLA-DQA1*05 allele. Researchers reviewed the IBD database and electronic medical record to ascertain the patients’ IBD phenotype, their use of biologic therapies, drug levels for biologic agents, antibody levels, and the duration of their treatment. Using a drug-binding antibody assay, the team conducted statistical analyses to identify antidrug antibodies to infliximab, adalimumab, vedolizumab, and ustekinumab.

Of the 120 patients with available drug levels, the majority had ileocolonic Crohn disease (66.1%). They had received biologic therapy, on average, for 2.4 years. The researchers found that 30.8% of these Hispanic patients had antibodies to biologic agents. Of 85 patients taking infliximab, 22 (25.9%) developed antibodies; and 18 of 50 patients (36%) who had been treated with adalimumab also developed antidrug antibodies. Only 1 patient out of 18 who were treated with vedolizumab developed antibodies, while none of the 8 patients treated with ustekinumab developed antibodies. Among patients on monotherapy, 15 (17.6%) patients treated with infliximab, 15 (30%) patients treated with adalimumab, and 1 (5.6%) patient on vedolizumab developed antidrug antibodies.

“The results of our study suggest that HLA-DQA1*05 is seen in about a third of Hispanics with IBD, approaching the prevalence observed in Europeans,” Dr Ioannou said. “Carriage of HLA-DQA1*05 in Hispanics with IBD increases risk of antibody formation to anti-TNFs, illustrating the clinical value of this polymorphism in Hispanics. We also demonstrate that the rate of immunogenicity with VDZ and UST is low even in the face of HLA-DQA1*05 carriage.”

—Rebecca Mashaw

Reference:

Ioannou S, Beecham A, Gomez L, et al. Carriage of HLA-DQA1*05 in Hispanic IBD patients is common and also associated with development of antibodies to anti-TNFs but not other biologics. Talk presented at: American College of Gastroenterology 2020 Clinical Meeting. October 24, 2020. Virtual.