A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population Public Deposited

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Creator
  • White, I.R.
    • Other Affiliation: UCB Celltech
  • Kleinstein, S.E.
    • Other Affiliation: Columbia University
  • Praet, C.
    • Other Affiliation: UCB Pharma
  • Chamberlain, C.
    • Other Affiliation: UCB Celltech
  • McHale, D.
    • Other Affiliation: UCB Celltech
  • Maia, J.M.
    • Other Affiliation: Columbia University
  • Xie, P.
    • Other Affiliation: Columbia University
  • Goldstein, D.B.
    • Other Affiliation: Columbia University
  • Urban, T.J.
    • Affiliation: Eshelman School of Pharmacy
  • Shea, P.R.
    • Other Affiliation: Columbia University
Abstract
  • Certolizumab pegol (CZP) is a PEGylated Fc-free tumor necrosis factor (TNF) inhibitor antibody approved for use in the treatment of rheumatoid arthritis (RA), Crohn's disease, psoriatic arthritis, axial spondyloarthritis and psoriasis. In a clinical trial of patients with severe RA, CZP improved disease symptoms in approximately half of patients. However, variability in CZP efficacy remains a problem for clinicians, thus, the aim of this study was to identify genetic variants predictive of CZP response. We performed a genome-wide association study (GWAS) of 302 RA patients treated with CZP in the REALISTIC trial to identify common single nucleotide polymorphisms (SNPs) associated with treatment response. Wholeexome sequencing was also performed for 74 CZP extreme responders and non-responders within the same population, as well as 1546 population controls. No common SNPs or rare functional variants were significantly associated with CZP response, though a non-significant enrichment in the RA-implicated KCNK5 gene was observed. Two SNPs near spondin- 1 and semaphorin-4G approached genome-wide significance. The results of the current study did not provide an unambiguous predictor of CZP response.
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DOI
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  • Article
Rights statement
  • In Copyright
License
  • Attribution 3.0 United States
Journal title
  • PLoS ONE
Journal volume
  • 17
Journal issue
  • 4-Apr
Page start
  • e0261165
Language
  • English
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  • Publisher
ISSN
  • 1932-6203
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