Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis

Pharmacogenomics J. 2017 Oct;17(5):403-411. doi: 10.1038/tpj.2017.26. Epub 2017 Jun 13.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha