{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:42:50Z","timestamp":1782963770249,"version":"3.54.5"},"reference-count":50,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.es","elsevier.es","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Actas Dermo-Sifiliogr\u00e1ficas"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.ad.2024.12.026","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T02:30:43Z","timestamp":1744684243000},"page":"863-875","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy of Widely Used Topical Drugs for Rosacea: A Systematic Review and Meta-Analysis"],"prefix":"10.1016","volume":"116","author":[{"given":"X.","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ad.2024.12.026_bib0255","first-page":"CD003262","article-title":"Interventions for rosacea","volume":"4","author":"van Zuuren","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.ad.2024.12.026_bib0260","first-page":"907","article-title":"Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea","volume":"50","author":"Wilkin","year":"2004","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0265","first-page":"282","article-title":"Incidence and prevalence of rosacea: a systematic review and meta-analysis","volume":"179","author":"Gether","year":"2018","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0270","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1080\/09546634.2021.1959507","article-title":"Pulsed dye laser versus intense pulsed light for facial erythema of rosacea: a systematic review and meta-analysis","volume":"33","author":"Chang","year":"2022","journal-title":"J Dermatolog Treat"},{"key":"10.1016\/j.ad.2024.12.026_bib0275","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1111\/jdv.14349","article-title":"Swiss S1 guideline for the treatment of rosacea","volume":"31","author":"Anzengruber","year":"2017","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"10.1016\/j.ad.2024.12.026_bib0280","first-page":"316","article-title":"Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies","volume":"13","author":"Gold","year":"2014","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0285","first-page":"290","article-title":"Pivotal trial of the efficacy and safety of oxymetazoline cream 1.0% for the treatment of persistent facial erythema associated with rosacea: findings from the second REVEAL trial","volume":"17","author":"Baumann","year":"2018","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0290","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1001\/archderm.139.11.1444","article-title":"A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial","volume":"139","author":"Elewski","year":"2003","journal-title":"Arch Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0295","first-page":"909","article-title":"Treatment of rosacea with concomitant use of topical ivermectin 1% cream and brimonidine 0.33% gel: a randomized, vehicle-controlled study","volume":"16","author":"Gold","year":"2017","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0300","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/bjd.13408","article-title":"Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial","volume":"172","author":"Taieb","year":"2015","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0305","first-page":"1380","article-title":"Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials","volume":"13","author":"Gold","year":"2014","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0310","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.jaad.2020.01.043","article-title":"Minocycline 1.5% foam for the topical treatment of moderate to severe papulopustular rosacea: results of 2 phase 3, randomized, clinical trials","volume":"82","author":"Gold","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0315","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/bjd.18857","article-title":"A multicentre, randomized, double-masked, parallel group, vehicle-controlled phase IIb study to evaluate the safety and efficacy of 1% and 3% topical minocycline gel in patients with papulopustular rosacea","volume":"183","author":"Webster","year":"2020","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0320","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s40257-017-0339-0","article-title":"A phase II, randomized, double-blind clinical study evaluating the safety, tolerability, and efficacy of a topical minocycline foam, FMX103, for the treatment of facial papulopustular rosacea","volume":"19","author":"Mrowietz","year":"2018","journal-title":"Am J Clin Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0325","unstructured":"Nct. A study to evaluate safety and equivalence of generic azelaic acid foam and Finacea\u00ae foam in patients with rosacea; 2017. https:\/\/clinicaltrials.gov\/study\/NCT03287791."},{"key":"10.1016\/j.ad.2024.12.026_bib0330","first-page":"54","article-title":"A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea","volume":"96","author":"Draelos","year":"2015","journal-title":"Cutis"},{"key":"10.1016\/j.ad.2024.12.026_bib0335","unstructured":"Nct. A study to evaluate the safety and clinical study of azelaic acid gel 15% in patients with moderate facial rosacea; 2014. https:\/\/clinicaltrials.gov\/study\/NCT03287791."},{"key":"10.1016\/j.ad.2024.12.026_bib0340","first-page":"306","article-title":"Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study","volume":"92","author":"Draelos","year":"2013","journal-title":"Cutis"},{"key":"10.1016\/j.ad.2024.12.026_bib0345","unstructured":"Nct. Safety and efficacy of azelaic acid foam, 15% in papulopustular rosacea; 2012. https:\/\/clinicaltrials.gov\/study\/NCT01555463."},{"key":"10.1016\/j.ad.2024.12.026_bib0350","first-page":"607","article-title":"Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40mg versus metronidazole gel 1% plus oral doxycycline 40mg in mild-to-moderate papulopustular rosacea","volume":"9","author":"Del Rosso","year":"2010","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0355","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1067\/mjd.2003.308","article-title":"Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies","volume":"48","author":"Thiboutot","year":"2003","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0360","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/1346-8138.16254","article-title":"Metronidazole gel (0.75%) in Japanese patients with rosacea: a randomized, vehicle-controlled, phase 3 study","volume":"49","author":"Miyachi","year":"2022","journal-title":"J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0365","first-page":"699","article-title":"Improvement in facial erythema within 30minutes of initial application of brimonidine tartrate in patients with rosacea","volume":"13","author":"Jackson","year":"2014","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0370","first-page":"650","article-title":"Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies","volume":"12","author":"Fowler","year":"2013","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0375","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1365-2133.2011.10716.x","article-title":"Once-daily topical brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies","volume":"166","author":"Fowler","year":"2012","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0380","first-page":"97","article-title":"Pivotal trial of the efficacy and safety of oxymetazoline cream 1.0% for the treatment of persistent facial erythema associated with rosacea: findings from the first REVEAL trial","volume":"17","author":"Kircik","year":"2018","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0385","doi-asserted-by":"crossref","first-page":"e1361574","DOI":"10.1080\/19381980.2017.1361574","article-title":"Rosacea: epidemiology, pathogenesis, and treatment","volume":"9","author":"Rainer","year":"2017","journal-title":"Dermatoendocrinology"},{"key":"10.1016\/j.ad.2024.12.026_bib0390","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.2174\/1874467214666210210122628","article-title":"Minocycline and doxycycline: more than antibiotics","volume":"14","author":"Singh","year":"2021","journal-title":"Curr Mol Pharmacol"},{"key":"10.1016\/j.ad.2024.12.026_bib0395","first-page":"CD002086","article-title":"Minocycline for acne vulgaris: efficacy and safety","volume":"2012","author":"Garner","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.ad.2024.12.026_bib0400","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3390\/antibiotics10070757","article-title":"A review of systemic minocycline side effects and topical minocycline as a safer alternative for treating acne and rosacea","volume":"10","author":"Martins","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"10.1016\/j.ad.2024.12.026_bib0405","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1208\/s12249-014-0118-7","article-title":"Comparative study to investigate the effect of meloxicam or minocycline HCl in situ gel system on local treatment of periodontal pockets","volume":"15","author":"Kassem","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.ad.2024.12.026_bib0410","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1086\/598510","article-title":"Doxycycline, not minocycline, induces its own resistance in multidrug-resistant, community-associated methicillin-resistant Staphylococcus aureus clone USA300","volume":"48","author":"Schwartz","year":"2009","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.ad.2024.12.026_bib0415","first-page":"346","article-title":"Evaluation of topical metronidazole gel in acne rosacea","volume":"21","author":"Aronson","year":"1987","journal-title":"Drug Intell Clin Pharm"},{"key":"10.1016\/j.ad.2024.12.026_bib0420","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1211\/jpp.59.8.0010","article-title":"Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system","volume":"59","author":"Narayanan","year":"2007","journal-title":"J Pharm Pharmacol"},{"key":"10.1016\/j.ad.2024.12.026_bib0425","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/j.1365-2133.2011.10473.x","article-title":"Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review","volume":"165","author":"van Zuuren","year":"2011","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0430","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1365-2133.1983.tb03972.x","article-title":"Treatment of rosacea with 1% metronidazole cream. A double-blind study","volume":"108","author":"Nielsen","year":"1983","journal-title":"Br J Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0435","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1001\/archderm.1987.01660290077020","article-title":"Topical metronidazole therapy for rosacea","volume":"123","author":"Bleicher","year":"1987","journal-title":"Arch Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0440","first-page":"44","article-title":"A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea","volume":"61","author":"Breneman","year":"1998","journal-title":"Cutis"},{"key":"10.1016\/j.ad.2024.12.026_bib0445","first-page":"283","article-title":"Topical metronidazole for severe and recalcitrant rosacea: a prospective open trial","volume":"43","author":"Lowe","year":"1989","journal-title":"Cutis"},{"key":"10.1016\/j.ad.2024.12.026_bib0450","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1472-8206.2009.00684.x","article-title":"Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway","volume":"23","author":"Ci","year":"2009","journal-title":"Fundam Clin Pharmacol"},{"key":"10.1016\/j.ad.2024.12.026_bib0455","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1111\/jdv.14437","article-title":"Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea","volume":"31","author":"Schaller","year":"2017","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"10.1016\/j.ad.2024.12.026_bib0460","doi-asserted-by":"crossref","first-page":"e13203","DOI":"10.1111\/dth.13203","article-title":"Efficacy of topical ivermectin and impact on quality of life in patients with papulopustular rosacea: a systematic review and meta-analysis","volume":"33","author":"Husein-ElAhmed","year":"2020","journal-title":"Dermatol Ther"},{"key":"10.1016\/j.ad.2024.12.026_bib0465","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s13555-018-0249-y","article-title":"Topical ivermectin in the treatment of papulopustular rosacea: a systematic review of evidence and clinical guideline recommendations","volume":"8","author":"Ebbelaar","year":"2018","journal-title":"Dermatol Ther (Heidelb)"},{"key":"10.1016\/j.ad.2024.12.026_bib0470","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1517\/14656566.9.15.2699","article-title":"Azelaic acid 15% gel in the treatment of rosacea","volume":"9","author":"Gollnick","year":"2008","journal-title":"Expert Opin Pharmacother"},{"key":"10.1016\/j.ad.2024.12.026_bib0475","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/jac\/34.3.321","article-title":"Disruption of the transmembrane pH gradient \u2013 a possible mechanism for the antibacterial action of azelaic acid in Propionibacterium acnes and Staphylococcus epidermidis","volume":"34","author":"Bojar","year":"1994","journal-title":"J Antimicrob Chemother"},{"key":"10.1016\/j.ad.2024.12.026_bib0480","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/BF00372056","article-title":"Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases","volume":"283","author":"Akamatsu","year":"1991","journal-title":"Arch Dermatol Res"},{"key":"10.1016\/j.ad.2024.12.026_bib0485","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jaad.2013.05.019","article-title":"Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel","volume":"69","author":"Coda","year":"2013","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0490","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.jaad.2014.08.027","article-title":"Rosacea: Part II. Topical and systemic therapies in the treatment of rosacea","volume":"72","author":"Two","year":"2015","journal-title":"J Am Acad Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0495","first-page":"56","article-title":"Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study","volume":"13","author":"Moore","year":"2014","journal-title":"J Drugs Dermatol"},{"key":"10.1016\/j.ad.2024.12.026_bib0500","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1007\/s12325-016-0404-8","article-title":"Multidisciplinary consideration of potential pathophysiologic mechanisms of paradoxical erythema with topical brimonidine therapy","volume":"33","author":"Docherty","year":"2016","journal-title":"Adv Ther"}],"container-title":["Actas Dermo-Sifiliogr\u00e1ficas"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0001731025002820?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0001731025002820?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:32:11Z","timestamp":1762075931000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0001731025002820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S0001731025002820"],"URL":"https:\/\/doi.org\/10.1016\/j.ad.2024.12.026","relation":{},"ISSN":["0001-7310"],"issn-type":[{"value":"0001-7310","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy of Widely Used Topical Drugs for Rosacea: A Systematic Review and Meta-Analysis","name":"articletitle","label":"Article Title"},{"value":"Actas Dermo-Sifiliogr\u00e1ficas","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ad.2024.12.026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 AEDV. Published by Elsevier Espa\u00f1a, S.L.U.","name":"copyright","label":"Copyright"}]}}