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Journal of Allergy and Clinical Immunology

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1 Journal of Allergy and Clinical Immunology
Modulation of inflammatory gene transcripts in psoriasis vulgaris: Differences between ustekinumab and etanercept  Carrie Brodmerkel, PhD, Katherine Li, MS, Sandra Garcet, PhD, Karen Hayden, PhD, Andrea Chiricozzi, PhD, Inna Novitskaya, PhD, Judilyn Fuentes-Duculan, MD, Mayte Suarez-Farinas, PhD, Kim Campbell, PhD, James G. Krueger, MD, PhD  Journal of Allergy and Clinical Immunology  DOI: /j.jaci Copyright © 2019 The Authors Terms and Conditions

2 Fig 1 Differential gene expression profiling of PASI75 responders to etanercept vs ustekinumab 90 mg (FCH ≥2, FDR ≤0.05). A, Venn diagram depicting the number of PSTR genes and DEGs significantly changed from baseline at week 12 (black: total number, red: increase, blue: decrease in DEGs). B, Means of the percentage of improvement at week 12 from baseline of PSTR genes by gene sets that define individual or consensus PSTR or cytokine-induced genes in cell cultures, as detailed in Table E5 in this article's Online Repository at and recently applied to psoriasis treatment with risankizumabE5 (n/N = number of PSTR genes/number of genes in pathway; red stars represent significance in contrast between treatments (*P ≤ .05, **P ≤ .01, ***P ≤ .001 derived from t tests). C, Boxplot of percentage of improvement by gene and direction, at week 12 (LSMs and SE in blue). D, Venn diagram of molecular scar at week 12. Percentage of PSTR genes with less than 75% of recovery. BL, Baseline; DEG, differentially-expressed genes; FCH, fold change; FDR, false-discovery rate; LS, lesional; LSM, least squares mean; NL, nonlesional; NR, nonresponder; PASI75, at least 75% improvement in the Psoriasis Area and Severity Index; PSTR, psoriasis transcriptome; R, responder. Journal of Allergy and Clinical Immunology DOI: ( /j.jaci ) Copyright © 2019 The Authors Terms and Conditions

3 Fig 2 Ingenuity pathway analysis of molecular scar (MS) sets of genes. For the top 10 pathways for etanercept only (A) and ustekinumab 90 mg only (B) and comparison of least squares mean of GVSA scores by pathway at MS genes (C), comparisons between etanercept only and ustekinumab 90 mg only used FCH greater or equal to 2 (W12-LS vs BL-NL) and FDR less or equal to 0.05 criteria. BL, Baseline; FCH, fold change; FDR, false-discovery rate; GSVA, gene set variation analysis; LS, lesional; MS, molecular scar; NL, nonlesional; W12, week 12. Journal of Allergy and Clinical Immunology DOI: ( /j.jaci ) Copyright © 2019 The Authors Terms and Conditions

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