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 neutralising 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.