{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:50:29Z","timestamp":1777477829287,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T00:00:00Z","timestamp":1685923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interleukin (IL)\u201023\u2013independent IL\u201017A production has been suggested to be involved in persistent manifestations of psoriatic disease, including anti\u2013IL\u201012\/23\u2013refractory psoriatic plaques; this study aimed to test this hypothesis by investigating the clinical and molecular effects of direct IL\u201017A (with secukinumab) versus selective IL\u201023 inhibition (with guselkumab) in patients with anti\u2013IL\u201012\/23 (ustekinumab)\u2013refractory psoriatic plaques. A 16\u2010week, randomized, open\u2010label, parallel\u2010group, Phase IIa study (ARROW, NCT03553823) was conducted in patients with \u22651 active psoriatic plaque (total clinical score [TCS] \u22656) at screening despite treatment with ustekinumab, and a Psoriasis Area and Severity Index (PASI) score 1\u201310. Patients were randomized 1:1 to receive secukinumab 300\u2009mg (<jats:italic>n<\/jats:italic>\u2009=\u200920) or guselkumab 100\u2009mg (<jats:italic>n<\/jats:italic>\u2009=\u200920). Biopsies from one refractory (\u2018target plaque\u2019) were obtained at baseline and Week 16. The primary endpoint was the proportion of patients whose ustekinumab\u2010refractory target plaque achieved clear\/almost clear status (TCS 0\u20132) at Week 16. Transcriptomic and histological analyses were conducted on target plaques to determine the molecular effects of direct IL\u201017A versus selective IL\u201023 inhibition. At Week 16, target plaque clear\/almost clear status was achieved in 60.0% of patients treated with secukinumab versus 40.0% of patients treated with guselkumab (<jats:italic>p<\/jats:italic>\u2009=\u20090.1715). Molecular analyses identified that secukinumab modulated a greater proportion of psoriasis disease transcriptome genes (72.1% vs. 48.0%) and resulted in more histological responders (72.2% vs. 53.3%) compared with guselkumab. Secukinumab demonstrated a greater clinical and molecular effect on ustekinumab\u2010refractory psoriatic plaques versus guselkumab. These results are consistent with the hypothesis that IL\u201023\u2013independent IL\u201017 mechanisms may be relevant to the inflammation driving refractory manifestations of psoriasis.<\/jats:p>","DOI":"10.1111\/exd.14828","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T21:01:56Z","timestamp":1686085316000},"page":"1834-1847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Secukinumab versus guselkumab in the complete resolution of ustekinumab\u2010resistant psoriatic plaques: The <scp>ARROW<\/scp> study"],"prefix":"10.1111","volume":"32","author":[{"given":"James","family":"Krueger","sequence":"first","affiliation":[{"name":"Laboratory of Investigative Dermatology The Rockefeller University  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard G.","family":"Langley","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Department of Medicine Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Nigen","sequence":"additional","affiliation":[{"name":"Sima Recherche, Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben","family":"Kasparek","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Di Comite","sequence":"additional","affiliation":[{"name":"Novartis Pharma K.K.  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