{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:16:08Z","timestamp":1789665368875,"version":"4.0.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":647,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Given the key role of the IL-23\/Th17 axis in the pathogenesis of moderate-to-severe plaque psoriasis, several specific inhibitors of the p19 subunit of IL-23 have been approved to treat this chronic inflammatory disease. Clinical data indicate that guselkumab, one such selective IL-23 inhibitor, achieves greater clinical efficacy compared with ustekinumab, which inhibits both IL-12 and IL-23 via binding their shared p40 subunit. To understand mechanisms underlying the enhanced efficacy observed with the p19 subunit of IL-23\u2013specific inhibition, we explored cellular and molecular changes in skin of psoriasis patients treated with ustekinumab or guselkumab and in ustekinumab inadequate responders (Investigator\u2019s Global Assessment of psoriasis score \u2265 2) subsequently treated with guselkumab (ustekinumab\u2192guselkumab). Skin biopsies were collected pretreatment and posttreatment to assess histologic changes and molecular responses in ustekinumab- and guselkumab-treated patients. Serum cytokines and skin transcriptomics from the subset of ustekinumab\u2192guselkumab-treated patients were also analyzed to characterize differential treatment effects. Ustekinumab and guselkumab demonstrated differential effects on secretion of pathogenic Th17-related cytokines induced by IL-23 in in vitro assays, which suggest guselkumab is a more potent therapeutic agent. Consistent with these findings, guselkumab elicited a significantly greater reduction in cellular and molecular psoriasis-related disease indicators than ustekinumab. In ustekinumab\u2192guselkumab patients, suppression of serum IL-17A and IL-17F levels and neutralization of molecular scar and psoriasis-related gene markers in skin were significantly greater compared with patients continuing ustekinumab. This comparative study demonstrates that guselkumab inhibits psoriasis-associated pathology, suppresses Th17-related serum cytokines, and normalizes the psoriasis skin gene expression profile more effectively than ustekinumab.<\/jats:p>","DOI":"10.4049\/immunohorizons.2300003","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T13:15:54Z","timestamp":1681823754000},"page":"273-285","source":"Crossref","is-referenced-by-count":18,"title":["Guselkumab More Effectively Neutralizes Psoriasis-Associated Histologic, Transcriptomic, and Clinical Measures than Ustekinumab"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3789-416X","authenticated-orcid":false,"given":"Kim","family":"Campbell","sequence":"first","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Li","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Yang","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-9067","authenticated-orcid":false,"given":"Patrick","family":"Branigan","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Merle","family":"Elloso","sequence":"additional","affiliation":[{"name":"Janssen Scientific Affairs, LLC , Horsham, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Benson","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevgeniya","family":"Orlovsky","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-6199","authenticated-orcid":false,"given":"Yanqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Garcet","sequence":"additional","affiliation":[{"name":"The Laboratory for Investigative Dermatology, The Rockefeller University , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G","family":"Krueger","sequence":"additional","affiliation":[{"name":"The Laboratory for Investigative Dermatology, The Rockefeller University , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"2025010703552354100_r1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-med-042915-103905","article-title":"Highly effective new treatments for psoriasis target the IL-23\/Type 17 T cell autoimmune axis","volume":"68","author":"Kim","year":"2017","journal-title":"Annu. Rev. Med."},{"key":"2025010703552354100_r2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/1744666X.2017.1292137","article-title":"The role of IL 23 in the treatment of psoriasis. [Published erratum appears in 2017 Exp. Rev. Clin. Immunol. 13: 6, ix.]","volume":"13","author":"Puig","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"2025010703552354100_r3","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1056\/NEJMoa0810652","article-title":"Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis","volume":"362","author":"Griffiths","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2025010703552354100_r4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jaad.2016.11.041","article-title":"Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. [Published erratum appears in 2017 J. Am. Acad. Dermatol. 76: 1226.]","volume":"76","author":"Blauvelt","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"2025010703552354100_r5","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/S0140-6736(08)60725-4","article-title":"Efficacy and safety of ustekinumab, a human interleukin-12\/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)","volume":"371","author":"Leonardi","year":"2008","journal-title":"Lancet"},{"key":"2025010703552354100_r6","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/S0140-6736(08)60726-6","article-title":"Efficacy and safety of ustekinumab, a human interleukin-12\/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)","volume":"371","author":"Papp","year":"2008","journal-title":"Lancet"},{"key":"2025010703552354100_r7","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.jaad.2015.07.002","article-title":"Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study","volume":"73","author":"Landells","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"2025010703552354100_r8","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1056\/NEJMoa1503824","article-title":"Phase 3 studies comparing brodalumab with ustekinumab in psoriasis","volume":"373","author":"Lebwohl","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"2025010703552354100_r9","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s13555-018-0265-y","article-title":"Secukinumab is superior to ustekinumab in clearing skin in patients with moderate to severe plaque psoriasis (16-week CLARITY results)","volume":"8","author":"Bagel","year":"2018","journal-title":"Dermatol. Ther. (Heidelb.)"},{"key":"2025010703552354100_r10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S1074-7613(00)00070-4","article-title":"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12","volume":"13","author":"Oppmann","year":"2000","journal-title":"Immunity"},{"key":"2025010703552354100_r11","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1111\/bjd.20568","article-title":"Five-year maintenance of clinical response and health-related quality of life improvements in patients with moderate-to-severe psoriasis treated with guselkumab: results from VOYAGE 1 and VOYAGE 2","volume":"185","author":"Reich","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"2025010703552354100_r12","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00228-016-2110-5","article-title":"First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics\/safety in healthy subjects and patients with moderate-to-severe psoriasis","volume":"72","author":"Zhuang","year":"2016","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"2025010703552354100_r13","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/bjd.15750","article-title":"Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial","volume":"178","author":"Langley","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"2025010703552354100_r14","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.jaci.2014.01.025","article-title":"Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis","volume":"133","author":"Sofen","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025010703552354100_r15","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.cyto.2014.11.018","article-title":"IL12R\u03b21: the cytokine receptor that we used to know","volume":"71","author":"Robinson","year":"2015","journal-title":"Cytokine"},{"key":"2025010703552354100_r16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.jmb.2010.07.046","article-title":"Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab","volume":"402","author":"Luo","year":"2010","journal-title":"J. Mol. Biol."},{"key":"2025010703552354100_r17","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nbt.1903","article-title":"Therapeutic targeting of the IL-12\/23 pathways: generation and characterization of ustekinumab","volume":"29","author":"Benson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"2025010703552354100_r18","doi-asserted-by":"crossref","first-page":"e44274","DOI":"10.1371\/journal.pone.0044274","article-title":"Meta-analysis derived (MAD) transcriptome of psoriasis defines the \u201ccore\u201d pathogenesis of disease","volume":"7","author":"Tian","year":"2012","journal-title":"PLoS One"},{"key":"2025010703552354100_r19","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.jaci.2019.01.017","article-title":"Modulation of inflammatory gene transcripts in psoriasis vulgaris: differences between ustekinumab and etanercept","volume":"143","author":"Brodmerkel","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025010703552354100_r20","article-title":"Tremfya (guselkumab): U.S. prescribing information","author":"U.S. Food and Drug Administration","year":"2017"},{"key":"2025010703552354100_r21","article-title":"Summary of product characteristics: Tremfya (guselkumab) 100 mg solution for injection","author":"U.S. Food and Drug Administration","year":"2017"},{"key":"2025010703552354100_r22","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jaad.2016.11.042","article-title":"Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. [Published erratum appears in 2017 J. Am. Acad. Dermatol. 76: 1226.]","volume":"76","author":"Reich","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"2025010703552354100_r23","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/bjd.16008","article-title":"Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies","volume":"178","author":"Gordon","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"2025010703552354100_r24","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1001\/jamadermatol.2018.0793","article-title":"Efficacy of guselkumab compared with adalimumab and placebo for psoriasis in specific body regions: a secondary analysis of 2 randomized clinical trials","volume":"154","author":"Foley","year":"2018","journal-title":"JAMA Dermatol."},{"key":"2025010703552354100_r25","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S0140-6736(19)31773-8","article-title":"Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial","volume":"394","author":"Reich","year":"2019","journal-title":"Lancet"},{"key":"2025010703552354100_r26","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/S0140-6736(18)31713-6","article-title":"Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials","volume":"392","author":"Gordon","year":"2018","journal-title":"Lancet"},{"key":"2025010703552354100_r27","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1016\/j.jaci.2018.11.042","article-title":"Psoriatic skin molecular and histopathologic profiles after treatment with risankizumab versus ustekinumab","volume":"143","author":"Visvanathan","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"2025010703552354100_r28","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00281-019-00766-z","article-title":"Resolution of plaque-type psoriasis: what is left behind (and reinitiates the disease)","volume":"41","author":"Benezeder","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"2025010703552354100_r29","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nature01355","article-title":"Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain","volume":"421","author":"Cua","year":"2003","journal-title":"Nature"},{"key":"2025010703552354100_r30","doi-asserted-by":"crossref","first-page":"13466","DOI":"10.1038\/ncomms13466","article-title":"IL-12 protects from psoriasiform skin inflammation","volume":"7","author":"Kulig","year":"2016","journal-title":"Nat. Commun."},{"key":"2025010703552354100_r31","first-page":"CD011535","article-title":"Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis","volume":"4","author":"Sbidian","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"2025010703552354100_r32","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.7326\/M22-1460","article-title":"Good publication practice (GPP) guidelines for company-sponsored biomedical research: 2022 update","volume":"175","author":"DeTora","year":"2022","journal-title":"Ann Intern Med"}],"container-title":["ImmunoHorizons"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/7\/4\/273\/60188734\/ih2300003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article-pdf\/7\/4\/273\/60188734\/ih2300003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T04:03:56Z","timestamp":1736222636000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/immunohorizons\/article\/7\/4\/273\/7816930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/immunohorizons.2300003","relation":{},"ISSN":["2573-7732"],"issn-type":[{"value":"2573-7732","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4]]},"published":{"date-parts":[[2023,4,1]]}}}