{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:55:05Z","timestamp":1791284105767,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Actinic keratosis (\n AK<\/jats:styled-content>\n ) is an early\n in\u00a0situ<\/jats:italic>\n epidermal cancer which can progress to invasive squamous cell carcinoma (\n SCC<\/jats:styled-content>\n ). Imiquimod 5% cream (\n IMIQ<\/jats:styled-content>\n ) and diclofenac 3% gel (\n DIC<\/jats:styled-content>\n ) are frequently used to treat\n AK<\/jats:styled-content>\n ; however, their long\u2010term effects following repeated treatment cycles have never been compared.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To compare\n IMIQ<\/jats:styled-content>\n and\n DIC<\/jats:styled-content>\n in the treatment of\n AK<\/jats:styled-content>\n with respect to the risk of change to grade\n III AK<\/jats:styled-content>\n or invasive\n SCC<\/jats:styled-content>\n , after 3\u00a0years.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Data were pooled from two randomized, active\u2010controlled, open\u2010label, multicentre, multinational, phase\n IV<\/jats:styled-content>\n studies (Clinicaltrials.gov\n NCT<\/jats:styled-content>\n 00777127\/\n NCT<\/jats:styled-content>\n 01453179), with two parallel groups. Studies were conducted between 2008 and 2015 and were almost identical in design. Patients eligible for inclusion were immunocompetent adults with 5\u201310 visible\n AK<\/jats:styled-content>\n lesions on the face\/scalp and grade I\/\n II AK<\/jats:styled-content>\n . The primary endpoint was inhibition of histological change to grade\n III AK<\/jats:styled-content>\n or invasive\n SCC<\/jats:styled-content>\n in the study treatment area, observed until month 36. Patients applied either\n IMIQ<\/jats:styled-content>\n or\n DIC<\/jats:styled-content>\n for a maximum of six treatment cycles.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In total, 479 patients (\n IMIQ<\/jats:styled-content>\n 242;\n DIC<\/jats:styled-content>\n 237) were included in the full analysis set. Histological change to grade\n III AK<\/jats:styled-content>\n or invasive\n SCC<\/jats:styled-content>\n was observed until month 36 in 13 (5.4%) patients treated with\n IMIQ<\/jats:styled-content>\n , compared with 26 (11.0%) patients treated with\n DIC<\/jats:styled-content>\n (absolute risk difference \u20135.6% [95% confidence interval \u201310.7%, \u20130.7%]). Time to histological change was greater in the\n IMIQ<\/jats:styled-content>\n group than the\n DIC<\/jats:styled-content>\n group (\n P\u00a0<\/jats:italic>\n =\n \u00a0<\/jats:italic>\n 0.0266). Frequency of progression to invasive\n SCC<\/jats:styled-content>\n was lower with\n IMIQ<\/jats:styled-content>\n than with\n DIC<\/jats:styled-content>\n at all time points. Initial clearance rate was higher in the\n IMIQ<\/jats:styled-content>\n group compared with the\n DIC<\/jats:styled-content>\n group, while recurrence rate was lower. Both treatments were well tolerated.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Over 3\u00a0years,\n IMIQ<\/jats:styled-content>\n was superior to\n DIC<\/jats:styled-content>\n in clearing\n AK<\/jats:styled-content>\n lesions and preventing histological change to grade\n III AK<\/jats:styled-content>\n or invasive\n SCC<\/jats:styled-content>\n and recurrence.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jdv.15868","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T03:29:35Z","timestamp":1565666975000},"page":"82-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Long\u2010term clinical outcomes of imiquimod 5% cream vs. diclofenac 3% gel for actinic keratosis on the face or scalp: a pooled analysis of two randomized controlled trials"],"prefix":"10.1111","volume":"34","author":[{"given":"H.","family":"Gollnick","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology Otto\u2010von\u2010Guericke University Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Dirschka","sequence":"additional","affiliation":[{"name":"Centroderm Clinic Wuppertal Germany"},{"name":"Faculty of Health University of Witten\u2010Herdecke Witten Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ostendorf","sequence":"additional","affiliation":[{"name":"Zentderma M\u00f6nchengladbach Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kerl","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Kunstfeld","sequence":"additional","affiliation":[{"name":"Dermatology Clinic General Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"43","article-title":"Actinic keratoses: a comprehensive update","volume":"2","author":"Ibrahim SF","year":"2009","journal-title":"J Clin Aesthet Dermatol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2004.11.015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-014-0049-y"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15107"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12848"},{"key":"e_1_2_8_7_1","first-page":"3","article-title":"Actinic keratosis and field cancerisation","volume":"21","author":"Stockfleth E","year":"2011","journal-title":"Eur J Dermatol"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-5-7"},{"key":"e_1_2_8_9_1","first-page":"36","article-title":"Mechanism of action and other potential roles of an immune response modifier","volume":"79","author":"Gaspari AA","year":"2007","journal-title":"Cutis"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.107808"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djg016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000254893"},{"key":"e_1_2_8_13_1","first-page":"241","article-title":"The use of topical imiquimod for the treatment of actinic keratosis: a status report","volume":"76","author":"Rosso JQ","year":"2005","journal-title":"Cutis"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08271.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07855.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07856.x"},{"key":"e_1_2_8_17_1","first-page":"600","article-title":"Diclofenac sodium 3% gel for the management of actinic keratosis: 10\u00a0+\u00a0years of cumulative evidence of efficacy and safety","volume":"11","author":"Martin GM","year":"2012","journal-title":"J Drugs Dermatol"},{"key":"e_1_2_8_18_1","first-page":"20","article-title":"Long\u2010term follow up of diclofenac sodium 3% in 2.5% hyaluronic acid gel for actinic keratosis: One\u2010year evaluation","volume":"2","author":"Nelson C","year":"2009","journal-title":"J Clin Aesthet Dermatol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.140.12.1542-a"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2005.31608"},{"key":"e_1_2_8_21_1","first-page":"677","article-title":"Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5\u2010year long\u2010term follow\u2010up study in Europe","volume":"18","author":"Gollnick H","year":"2008","journal-title":"Eur J Dermatol"},{"key":"e_1_2_8_22_1","first-page":"374","article-title":"Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2\u2010year results from an ongoing 5\u2010year follow\u2010up study in Europe","volume":"15","author":"Gollnick H","year":"2005","journal-title":"Eur J Dermatol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2010.03999.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546630701818870"},{"key":"e_1_2_8_25_1","unstructured":"Meda Pharmaceuticals.Aldara 5% cream (imiquimod) Summary of Product Characteristics (SmPC). URLhttps:\/\/www.medicines.org.uk\/emc\/product\/823\/smpc(last accessed 8 October 2018)."},{"key":"e_1_2_8_26_1","unstructured":"Almirall Ltd.Solaraze\u2122 3% gel (diclofenac sodium) Summary of Product Characteristics (SmPC). URLhttps:\/\/www.medicines.org.uk\/emc\/product\/6385\/smpc(last accessed 8 October 2018)."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07860.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.07121.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14512"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16536"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12824"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.01047.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.343"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-8749(02)00517-8"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13626"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33952"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.15868","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jdv.15868","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.15868","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:31:24Z","timestamp":1791282684000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.15868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,12]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/jdv.15868"],"URL":"https:\/\/doi.org\/10.1111\/jdv.15868","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,12]]},"assertion":[{"value":"2019-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}