{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:04:24Z","timestamp":1758931464753,"version":"3.44.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"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. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the efficacy of biologics in psoriasis treatment, their contraindications limit accessibility. Traditional systemic agents like cyclosporine A (CsA) and acitretin remain first-line options for long-term management, yet evidence on their combined use is scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this randomized controlled trial, patients with moderate-to-severe plaque psoriasis were assigned to CsA\u202f+\u202facitretin combination therapy, CsA monotherapy, or acitretin monotherapy. Treatment lasted 12\u201316\u202fweeks with follow-up to week 24. The primary outcomes were the proportions of patients achieving at least a 75% (PASI75) and 90% (PASI90) reduction from baseline in the Psoriasis Area and Severity Index (PASI). Secondary outcomes included mean change in PASI, Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), and adverse events (AEs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 351 screened patients, 345 were randomized and 305 completed the study. Combination therapy achieved significantly faster and greater responses than monotherapies. At week 4, &amp;gt;60% of patients in the combination group achieved PASI75 versus &amp;lt;25% in either monotherapy arm (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), and 21.6% achieved PASI90 compared with almost none (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). These advantages were maintained at week 12 (PASI75, 89.2%; PASI90, 66.7%) and sustained at week 24 (91.2 and 77.5%, respectively). BSA and DLQI improvements paralleled PASI, with greater early benefits in the combination group that converged after week 12. Combination therapy also maintained efficacy with lower mean doses of both CsA and acitretin. Most AEs were mild and reversible: dryness and dyslipidemia were more frequent with acitretin, hypertension with CsA, and hepatic abnormalities higher with combination therapy, though not significant. Overall, combination therapy demonstrated an acceptable safety profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CsA\u2013acitretin combination therapy demonstrated superior early efficacy and acceptable tolerability compared with monotherapies while reducing drug exposure. This regimen may represent a cost-effective therapeutic option for patients not eligible for biologic therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>https:\/\/www.chictr.org.cn<\/jats:uri>, ID register: ChiCTR-OPN-17013383.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1667058","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T05:31:15Z","timestamp":1758864675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of cyclosporine a combined with acitretin in moderate-to-severe plaque psoriasis: a randomized controlled trial"],"prefix":"10.3389","volume":"12","author":[{"given":"Kang","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujie","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingjie","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.jaad.2019.10.051","article-title":"Predictors 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