Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis

Sci Rep. 2024 Mar 21;14(1):6763. doi: 10.1038/s41598-024-56987-2.

Abstract

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10-3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Keywords: Abatacept; Amino acid; HLA-DRB1; Seropositive rheumatoid arthritis; TNF inhibitors; Treatment response.

MeSH terms

  • Abatacept / genetics
  • Abatacept / pharmacology
  • Abatacept / therapeutic use
  • Alleles
  • Amino Acids / genetics
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / genetics
  • Epitopes / genetics
  • Genetic Predisposition to Disease
  • HLA-DRB1 Chains / genetics
  • Humans
  • Tumor Necrosis Factor Inhibitors* / therapeutic use

Substances

  • Abatacept
  • HLA-DRB1 Chains
  • Tumor Necrosis Factor Inhibitors
  • Epitopes
  • Amino Acids