Crohn’s Disease Patients with HLA-DQA1*05 Allele at Increased Risk of Antidrug Antibody Development
Monika Fischer, MD, reviewing Sazonovs A, et al. Gastroenterology 2020 Jan.
In this genome-wide association study, 1240 patients with biologic-naive Crohn’s disease were treated with either infliximab or adalimumab with or without concomitant immunomodulator therapy. They were then longitudinally followed for the development of antidrug antibodies as well as loss of response to therapy. The HLA-DQA1*05 allele was identified to increase the risk by 2-fold. Carriers of HLA-DQA1*05 allele on infliximab monotherapy developed antidrug antibody in 92% of the cases at 1 year; whereas, patients who did not carry this allele and were on adalimumab in combination with an immunomodulatory developed antibodies at a 10% rate at 1 year.
COMMENT
This is the first study to propose a useful biomarker to predict response to an anti-tumor necrosis factor (anti-TNF) drug. While we await results of upcoming randomized trials, the results in this study are robust enough to potentially alter clinical practice. It is reasonable to test patients with Crohn’s disease for HLA-DQA1*05 prior to initiating biologic therapy.The HLA-DQA1*05 allele is associated with celiac disease. It is included in the panel of celiac-gene testing and readily available in most labs. Patients who carry this allele (estimated to be 40% of whites) may not be ideal candidates for anti-TNF monotherapy. They may develop antidrug antibodies and lose response quickly. If anti-TNF therapy appears to be the best choice for these patients, then adalimumab should be considered (100% human, less immunogenic) instead of infliximab, and should be prescribed in combination with immunomodulator therapy.
Monika Fischer, MD, FASGE
CITATION(S )
Sazonovs A, Kennedy NA, Moutsianas L, et al; PANTS Consortium. HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn’s disease. Gastroenterology 2020 Jan;158:189-199. (https://doi.org/10.1053/j.gastro.2019.09.041)
