HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy.
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