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- Title
A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population.
- Authors
White, Ian R.; Kleinstein, Sarah E.; Praet, Christophe; Chamberlain, Chris; McHale, Duncan; Maia, Jessica M.; Pingxing Xie; Goldstein, David B.; Urban, Thomas J.; Shea, Patrick R.
- 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.
- Subjects
CERTOLIZUMAB pegol; RHEUMATOID arthritis; GENETIC variation; GENOME-wide association studies; TUMOR necrosis factors; CROHN'S disease
- Publication
PLoS ONE, 2022, Vol 17, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0261165