HLA Class II Alleles are associated with Anti-Drug Antibodies in Ulcerative Colitis Patients Treated with Etrolizumab

Patients treated with etrolizumab, a monoclonal antibody drug for ulcerative colitis, often develop anti-drug antibodies (ADA) and neutralizing antibodies (NAb). To investigate genetic risk factors, we evaluated associations between HLA alleles and ADA/NAb development. HLA-DQB1*06:03 demonstrated the most significant association with both ADA (OR = 7.3, P ≤ 7.6×10 −13 ) and NAb (OR = 13.1, P ≤ 7.7×10 −13 ). After controlling for HLA-DQB1*06:03, HLA-DQA1*03:03 emerged as the next most significant allele associated with ADA (OR = 2.8, P ≤ 1.0×10 −3 ) and NAb (OR = 5.0, P ≤ 1.3×10 −3 ). Notably, all patients carrying both alleles (n=5) developed ADA, suggesting these two alleles are sufficient to induce ADA to etrolizumab.