Pathway analysis to identify genetic variants associated with efficacy of adalimumab in rheumatoid arthritis

Pharmacogenomics. 2017 Jul;18(10):945-953. doi: 10.2217/pgs-2017-0047. Epub 2017 Jun 22.

Abstract

Aim: About 30% of rheumatoid arthritis patients have no clinical benefit from TNF inhibitors. Genome-wide association (GWA) and candidate gene studies tested several putative genetic variants for TNF inhibitor efficacy with inconclusive results. Therefore, this study applied a systematic pathway analysis.

Patients & methods: A total of 325 rheumatoid arthritis patients treated with adalimumab were genotyped for 223 SNPs. We tested the association between SNPs and European League Against Rheumatism response and remission at 14 weeks under the additive genetic model using logistic regression.

Results: A total of 3 SNPs located in CD40LG (rs1126535), TANK (rs1267067) and VEGFA (rs25648) showed association with both end points. TNFAIP3 (rs2230926) had the strongest effect related to European League Against Rheumatism response.

Conclusion: This exploratory study suggests that TNFAIP3, CD40LG, TANK and VEGFA play a role in the response to adalimumab treatment.

Keywords: adalimumab; efficacy; genetics; rheumatoid arthritis.

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / therapeutic use*
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Cohort Studies
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Models, Genetic
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Adalimumab