TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis

Sci Rep. 2016 Aug 31:6:32202. doi: 10.1038/srep32202.

Abstract

While previous studies have researched in association analyses between TNFα promoter polymorphisms and responses to TNF blockers in spondyloarthritis patients, their results were conflicting. Therefore, we aimed to determine whether TNFα promoter polymorphisms could predict response to TNF blockers and find the source of heterogeneity. Data were extracted and analyzed from published articles and combined with our unpublished data. We found that the greatest potential sources of heterogeneity in the results were gender ratio, disease type, continents, and TNF blockers. Then Stratification analysis showed that the TNFα -308 G allele and the -238 G allele predicted a good response to TNF blockers (OR = 2.64 [1.48-4.73]; 2.52 [1.46-4.37]). However, G alleles of TNFα -308 and -238 could predict the response to etanercept (OR = 4.02 [2.24-7.23]; 5.17 [2.29-11.67]) much more powerfully than the response to infiliximab/adalimumab (OR = 1.68 [1.02-2.78]; 1.28 [0.57-2.86]). TNFα -857 could not predict the response in either subgroup. Cumulative meta-analysis performed in ankylosing spondylitis patients presented the odds ratio decreased with stricter response criteria. In conclusion, TNFα -308 A/G and -238 A/G are more powerful to predict the response to Etanercept and it is dependent on the criteria of response.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adalimumab / administration & dosage*
  • Alleles*
  • Etanercept / administration & dosage*
  • Female
  • Humans
  • Infliximab / administration & dosage*
  • Male
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Promoter Regions, Genetic*
  • Spondylitis, Ankylosing* / drug therapy
  • Spondylitis, Ankylosing* / genetics
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept