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 [≤] 7.6x10-13) and NAb (OR = 13.1, P [≤] 7.7x10-13). 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 [≤] 1.0x10-3) and NAb (OR = 5.0, P [≤] 1.3x10-3). Notably, all patients carrying both alleles (n=5) developed ADA, suggesting these two alleles are sufficient to induce ADA to etrolizumab.