Polymorphism at position -308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis

Arthritis Rheum. 2003 Jul;48(7):1849-52. doi: 10.1002/art.11168.

Abstract

Objective: To test whether the G-to-A polymorphism at position -308 in the promoter of the tumor necrosis factor alpha (TNFalpha) gene influences response to infliximab therapy in patients with rheumatoid arthritis (RA).

Methods: We genotyped 59 RA patients by polymerase chain reaction and subdivided them into two groups: those with the A/A or A/G genotype and those with the G/G genotype. We compared the groups' clinical responses to infliximab treatment after 22 weeks, using the Disease Activity Score in 28 joints (DAS28).

Results: We found that 42% of patients in the A/A and A/G group and 81% of patients in the G/G group had improvement of at least 1.2 in the DAS28 score (P = 0.0086). The average improvement in the DAS28 score was 1.24 in the A/A and A/G patients and 2.29 in the G/G patients (P = 0.029).

Conclusion: These data suggest that patients with a TNFalpha -308G/G genotype are better infliximab responders than are patients with A/A or A/G genotypes. TNFalpha -308 genotyping may be a useful tool for predicting response to infliximab treatment.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Female
  • Genotype
  • Humans
  • Infliximab
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Prospective Studies
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab