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

TLDR

The study aimed to determine whether the TNFα −308 G→A promoter polymorphism predicts response to infliximab in rheumatoid arthritis patients. Sixty patients were genotyped for the −308 polymorphism, divided into A/A or A/G versus G/G groups, and their DAS28 scores were compared after 22 weeks of infliximab therapy. Patients with the G/G genotype showed a significantly higher response (81% vs 42% with ≥1.2 DAS28 improvement, mean 2.29 vs 1.24) and the results suggest that −308 genotyping could predict infliximab efficacy.

Abstract

Abstract Objective To test whether the G‐to‐A polymorphism at position −308 in the promoter of the tumor necrosis factor α (TNFα) 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 TNFα −308G/G genotype are better infliximab responders than are patients with A/A or A/G genotypes. TNFα −308 genotyping may be a useful tool for predicting response to infliximab treatment.