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- W4295261903 abstract "Introduction: Guselkumab, an interleukin 23p19-subunit monoclonal antibody, demonstrated efficacy in psoriatic arthritis (PsA) in the phase-3 DISCOVER-1&2 trials. We evaluated gene expression in blood and the impact of guselkumab, using samples from these studies. Methods: Patients were treated with guselkumab 100 mg subcutaneously every 4 weeks (Q4W); guselkumab at W0, W4, then Q8W; or placebo. Whole-transcriptome profiling by RNA-sequencing used the Novaseq platform for baseline blood samples of a representative subset (n = 673) of patients across the 2 trials (with n = 227 evaluated over time) and for demographically matched healthy controls (HC, n = 21). Differentially expressed genes (DEGs, PsA vs HC) were identified at a false discovery rate (FDR) <0.05. Gene set enrichment scores were obtained using Gene Set Variation Analysis. Results: Comparison of whole-blood transcriptomes at baseline in patients with active PsA showed 355 upregulated and 314 downregulated genes vs HC. 82% of upregulated genes were decreased by guselkumab at Week 24, none increased. 77% of downregulated genes were increased by guselkumab, none decreased. These included genes related to B-, T-, NK-, and plasma cells (increased by guselkumab) and neutrophils, monocytes, eosinophils, and macrophages (decreased by guselkumab). Upon stratification by PASI75 and ACR20 response, changes in DEG expression from W0 to W4, W24 or to W24, respectively, were statistically significant among responders (P ≤ .05), but not nonresponders. Conclusions: Whole-transcriptome profiling detected DEGs in blood samples from PsA patients vs HC, suggesting a dysregulation of immune-cell profiles in PsA. The majority of these disease-associated genes were modulated by guselkumab toward normalization of whole blood transcriptomic signatures." @default.
- W4295261903 created "2022-09-12" @default.
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- W4295261903 date "2022-09-01" @default.
- W4295261903 modified "2023-10-04" @default.
- W4295261903 title "32938 Guselkumab treatment modulates genes differentially expressed in blood samples of patients with psoriatic arthritis vs healthy controls in two phase 3 clinical trials (DISCOVER-1 and -2)" @default.
- W4295261903 doi "https://doi.org/10.1016/j.jaad.2022.06.711" @default.
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