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Article Abstract
Ixekizumab, an IL-17A antagonist, and guselkumab, an IL-23p19 antagonist, are common psoriasis treatments. This longitudinal analysis assessed gene expression profiles in ixekizumab- and guselkumab-treated patients with plaque psoriasis through Week 4. In IXORA-R (NCT03573323), a head-to-head Phase 4 study, adults with moderate-to-severe plaque psoriasis were assigned 1:1 to receive ixekizumab or guselkumab. RNA expression was assessed in lesional tissue (N=72) from ixekizumab, guselkumab, and healthy control groups (199 samples total). Empirical Bayes modeled RNA-seq data; differential expression was analyzed by tissue type, treatment, and timepoint, correcting for random effects. At Week 1, lesions from ixekizumab-treated patients had greater numbers of differentially expressed genes (392 up-regulated, 696 down-regulated) than guselkumab-treated patients (0 up-regulated; 0 down-regulated). By Week 4, the numbers of differentially expressed genes increased in both groups (ixekizumab: 1,882 up-regulated, 1,649 down-regulated; guselkumab: 318 up-regulated, 131 down-regulated). Molecular shifts from baseline to Week 4 occurred earlier with greater magnitude in ixekizumab- versus guselkumab-treated patients. Rapid normalization of transcriptomic changes in patients receiving an IL-17A antagonist reflected down-regulation of key inflammatory genes in psoriatic epidermis. Differentially expressed genes involved in epidermal IL-17A and IL-36 responses correlated with PASI 100 response.
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| http://dx.doi.org/10.1016/j.jid.2025.06.1598 | DOI Listing |
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Comparative molecular analysis of IL-17A and IL-23 pathway inhibition in moderate-to-severe psoriasis: 4-week results from IXORA-R.
J Invest Dermatol
August 2025
Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, MI, US.
Ixekizumab, an IL-17A antagonist, and guselkumab, an IL-23p19 antagonist, are common psoriasis treatments. This longitudinal analysis assessed gene expression profiles in ixekizumab- and guselkumab-treated patients with plaque psoriasis through Week 4. In IXORA-R (NCT03573323), a head-to-head Phase 4 study, adults with moderate-to-severe plaque psoriasis were assigned 1:1 to receive ixekizumab or guselkumab.
View Article and Find Full Text PDFGuselkumab for the treatment of moderate-to-severe plaque psoriasis in paediatric patients: results of the phase III randomized placebo-controlled PROTOSTAR study.
Br J Dermatol
March 2025
Department of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies.
Lancet
January 2025
Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany.
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- Interleukin-23 inhibition is a promising treatment for ulcerative colitis, and guselkumab serves as a potent inhibitor targeting this pathway, aiming to assess its safety and effectiveness for patients who have not responded to traditional therapies.
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- Results showed that a significantly higher number of patients receiving guselkumab achieved clinical remission compared to those on placebo, highlighting its potential as an effective therapy for managing ulcerative colitis.
Guselkumab in Biologic-Naïve Patients with Active Psoriatic Arthritis in Russia: A Post Hoc Analysis of the DISCOVER-1 and -2 Randomized Clinical Trials.
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Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA.
Introduction: There are limited data on the use of advanced therapies to treat psoriatic arthritis (PsA) in Russia. Guselkumab, an interleukin (IL)-23p19-subunit inhibitor, demonstrated efficacy in patients with PsA in the phase 3 DISCOVER-1 and -2, and COSMOS trials. This analysis evaluated the efficacy and safety of guselkumab in patients with PsA in Russia.
View Article and Find Full Text PDFAssociation between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.
Clin Rheumatol
May 2024
Leeds Biomedical Research Centre, University of Leeds, 2nd Floor, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK.
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