Do genetics contribute to TNF inhibitor response prediction in Psoriatic Arthritis?

Philippa D K Curry, Andrew P Morris, Anne Barton, James Bluett

Research output: Contribution to journalReview articlepeer-review

Abstract

Psoriatic arthritis (PsA) is a heterogeneous chronic musculoskeletal disease, affecting up to 30% of people with psoriasis. Research into PsA pathogenesis has led to the development of targeted therapies, including Tumor Necrosis Factor inhibitors (TNF-i). Good response is only achieved by ~60% of patients leading to 'trial and error' drug management approaches, adverse reactions and increasing healthcare costs. Robust and well-validated biomarker identification, and subsequent development of sensitive and specific assays, would facilitate the implementation of a stratified approach into clinical care. This review will summarise potential genetic biomarkers for TNF-i (adalimumab, etanercept and infliximab) response that have been reported to date. It will also comment upon the importance of managing clinical confounders when understanding drug response prediction. Variants in multiple gene regions including TNF-A, FCGR2A, TNFAIP3, TNFR1/TNFR1A/TNFRSF1A, TRAIL-R1/TNFRSF10A, FCGR3A have been reported to correlate with TNF-i response at various levels of statistical significance in patients with PsA. However, results were often from heterogenous and underpowered cohorts and none are currently implemented into clinical practice. External validation of genetic biomarkers in large, well-documented cohorts is required, and assessment of the predictive value of combining multiple genetic biomarkers with clinical measures is essential to clinically embed pharmacogenomics into PsA drug management.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalThe pharmacogenomics journal
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2023

Keywords

  • Humans
  • Arthritis, Psoriatic/drug therapy
  • Tumor Necrosis Factor Inhibitors/therapeutic use
  • Antibodies, Monoclonal/adverse effects
  • Immunoglobulin G/therapeutic use
  • Etanercept/adverse effects
  • Infliximab/therapeutic use
  • Tumor Necrosis Factor-alpha/genetics
  • Adalimumab/therapeutic use
  • Antirheumatic Agents/adverse effects

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