Pharmacogenetics of TNF inhibitor response in rheumatoid arthritis utilizing the two-component disease activity score

Pharmacogenomics. 2020 Nov;21(16):1151-1156. doi: 10.2217/pgs-2020-0043. Epub 2020 Oct 30.

Abstract

Aim: TNF inhibitor drugs are a treatment option for rheumatoid arthritis, but response is not universal. Response is typically measured using the composite 4-component (4C) disease activity score 28 (DAS28) which contains more subjective measures. This study used a validated 2-component (2C) DAS28 score to determine whether SNPs associated with response were replicated in the UK population. Materials & methods: A literature review identified TNF inhibitor response SNPs. Linear regression was conducted to replicate associations with 4C or 2C-DAS28 response. Results: Eighteen independent SNPs were analyzed in 1828 patients. One and four associations with 4C and 2C-DAS28 response respectively were identified (p ≤ 0.05). Conclusion: Further genetic associations were replicated using the 2C-DAS28 which may reflect the objective nature of 2C-AS28.

Keywords: TNF inhibitors; biomarker; rheumatoid arthritis; single nucleotide polymorphism; treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Biomarkers
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Severity of Illness Index
  • Treatment Failure
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use*
  • Tumor Necrosis Factor-alpha
  • United Kingdom

Substances

  • Biomarkers
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha