{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:42:54Z","timestamp":1772779374122,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Biologic therapies targeting inflammatory cytokines have transformed the management of plaque psoriasis; however, their use is limited by high cost, parenteral administration, and monitoring requirements. Icotrokinra (JNJ-77242113) is a first-in-class oral peptide that selectively inhibits the interleukin-23 (IL-23) receptor and represents a potential oral alternative. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of oral icotrokinra in moderate-to-severe plaque psoriasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) published up to November 2025. Eligible studies enrolled adolescents or adults with moderate-to-severe plaque psoriasis treated with oral icotrokinra (200 mg once daily) versus placebo. A random-effects model was applied, and dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs). Risk of bias was assessed using RoB 2, and trial sequential analysis (TSA) was performed to evaluate the conclusiveness of evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five RCTs comprising 1,951 participants were included. At week 16, icotrokinra significantly improved Investigator\u2019s Global Assessment (IGA) 0\/1 (RR = 7.27, 95% CI 5.62\u20139.40) and Psoriasis Area and Severity Index (PASI) 75 responses (RR = 6.70, 95% CI 5.20\u20138.62) compared with placebo (both\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Higher levels of skin clearance were also achieved, including PASI 90 (RR = 13.82, 95% CI 8.75\u201321.84) and PASI 100 (RR = 31.65, 95% CI 12.56\u201379.76). Significant benefits were observed in scalp-specific disease (ss-IGA; RR = 4.27) and patient-reported outcomes, including complete symptom resolution on the Psoriasis Symptom Scale Diary (RR = 9.76). Adverse event rates did not differ significantly between icotrokinra and placebo, and heterogeneity across outcomes was minimal. TSA indicated that current evidence remains insufficient to confirm definitive conclusions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oral icotrokinra demonstrates potential efficacy across multiple clinical and patient-reported endpoints with a safety profile comparable to placebo in moderate-to-severe plaque psoriasis. However, TSA indicates that the required information size has not been reached. Therefore, current evidence remains insufficient to draw definitive conclusions. Future RCTs with long-term follow-up are required to confirm these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?RecordID=1237937<\/jats:ext-link>\n                      , identifier CRD420251237937\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1768292","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:31:02Z","timestamp":1772775062000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and efficacy of oral icotrokinra for moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.3389","volume":"17","author":[{"given":"Retaj S.","family":"AlJuma","sequence":"first","affiliation":[{"name":"College of Medicine and Medical Sciences, Arabian Gulf University","place":["Manama, Bahrain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayed","family":"Hashim","sequence":"additional","affiliation":[{"name":"Dermatology Department, Kuwait Institute for Medical Specializations","place":["Kuwait City, Kuwait"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malak Ahmed","family":"Alshamali","sequence":"additional","affiliation":[{"name":"Dermatology Department, Kuwait Institute for Medical Specializations","place":["Kuwait City, Kuwait"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shouq","family":"Alkhatlan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sheikh Jaber Al-Ahmad Al-Sabah Hospital, Ministry of Health","place":["Kuwait City, Kuwait"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danah Jamil","family":"Hammadi","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland \u2013 Medical University of Bahrain","place":["Alsayah, Bahrain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah M.","family":"Alharran","sequence":"additional","affiliation":[{"name":"College of Medicine and Medical Sciences, Arabian Gulf University","place":["Manama, Bahrain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13854","article-title":"A systematic review of worldwide epidemiology of psoriasis","volume":"31","author":"Michalek","year":"2017","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.11.013","article-title":"Psoriasis prevalence among adults in the United 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