{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:37:18Z","timestamp":1762659438965,"version":"3.37.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100023331","name":"LEO Pharma","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100023331","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ingenol mebutate (IngMeb) is a novel patient-applied topical field therapy for actinic keratosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To demonstrate the efficacy and safety of follow-up IngMeb field treatment of actinic keratoses (AKs) present at 8 weeks after initial treatment or emerging in a previously cleared field.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this phase III, randomized, double-blind study in patients with 4\u20138 clinically visible AKs within a contiguous 25-cm2 treatment area on the face or scalp, all patients were treated initially with IngMeb 0\u00b7015% gel for three consecutive days. If lesions were present in the field at 8 weeks, or emerged at weeks 26 or 44, patients were randomized (2 : 1) to follow-up IngMeb or vehicle gel for three consecutive days. The main outcome was complete clearance rates of AKs 8 weeks after randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 450 patients who received initial treatment with IngMeb, 61\u00b76% demonstrated complete clearance at 8 weeks. Patients with AKs present at 8 weeks or emerging at weeks 26 or 44 were randomized to IngMeb (n = 134) or vehicle (n = 69). IngMeb achieved a higher complete clearance rate than vehicle 8 weeks after randomization in AKs present at 8 weeks (46\u00b77% vs. 18\u00b74%; P &amp;lt; 0\u00b701) and in emergent AKs (59\u00b75% vs. 25\u00b70%; P = 0\u00b701). Based on those who completed 12 months of follow-up (n = 340), the overall 12-month clearance rate was estimated at 50\u00b70%. Follow-up IngMeb treatment was well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated the long-term benefit of IngMeb 0\u00b7015% gel for initial and follow-up therapy of AKs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bjd.14222","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T04:44:48Z","timestamp":1444970688000},"page":"505-513","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy and safety of follow-up field treatment of actinic keratosis with ingenol mebutate 0\u00b7015% gel: a randomized, controlled 12-month study"],"prefix":"10.1093","volume":"174","author":[{"given":"C.","family":"Garbe","sequence":"first","affiliation":[{"name":"Department of Dermatology Division of Dermatooncology University Hospital T\u00fcbingen T\u00fcbingen 72076 Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Basset-Seguin","sequence":"additional","affiliation":[{"name":"H\u00f4pital Saint-Louis Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Poulin","sequence":"additional","affiliation":[{"name":"Laval University Quebec City QC Canada"},{"name":"Center for Research in Dermatology Quebec City QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Larsson","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S Ballerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.L.","family":"\u00d8sterdal","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S Ballerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Venkata","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S Ballerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.T.","family":"Lear","sequence":"additional","affiliation":[{"name":"Department of Dermatology Manchester Royal Infirmary and Manchester Academics Health Science Centre Manchester University Manchester U.K"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1040-8428(01)00185-8","article-title":"Chemoprevention of human skin cancer","volume":"41","author":"Einspahr","year":"2002","journal-title":"Crit Rev Oncol Hematol"},{"issue":"Suppl. 2","key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1365-2133.2007.08268.x","article-title":"Management of field change in actinic keratosis","volume":"157","author":"Vatve","year":"2007","journal-title":"Br J Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1046\/j.1365-4362.1998.00467.x","article-title":"Frequency of pre-existing actinic keratosis in cutaneous squamous cell carcinoma","volume":"37","author":"Mittelbronn","year":"1998","journal-title":"Int J Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1177\/120347540200600301","article-title":"The majority of cutaneous squamous cell carcinomas arise in actinic keratoses","volume":"6","author":"Czarnecki","year":"2002","journal-title":"J Cutan Med Surg"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/jdv.12848","article-title":"Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin","volume":"29","author":"Fernandez-Figueras","year":"2015","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"Suppl. 1","key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jaad.2012.09.053","article-title":"Pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation","volume":"68","author":"Berman","year":"2013","journal-title":"J Am Acad Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/cncr.24284","article-title":"Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial","volume":"115","author":"Criscione","year":"2009","journal-title":"Cancer"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/bjd.12420","article-title":"The natural history of actinic keratosis: a systematic review","volume":"169","author":"Werner","year":"2013","journal-title":"Br J Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.1523-1747.2000.00048.x","article-title":"High incidence and regression rates of solar keratoses in a queensland community","volume":"115","author":"Frost","year":"2000","journal-title":"J Invest Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1056\/NEJMoa1111170","article-title":"Ingenol mebutate gel for actinic keratosis","volume":"366","author":"Lebwohl","year":"2012","journal-title":"N Engl J Med"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1001\/jamadermatol.2013.2766","article-title":"Long-term follow-up study of ingenol mebutate gel for the treatment of actinic keratoses","volume":"149","author":"Lebwohl","year":"2013","journal-title":"JAMA Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s13555-014-0059-9","article-title":"A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate","volume":"4","author":"Rosen","year":"2014","journal-title":"Dermatol Ther"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1016\/j.jaad.2012.09.051","article-title":"Current issues in the management of actinic keratosis","volume":"68","author":"Ceilley","year":"2013","journal-title":"J Am Acad Dermatol"},{"key":"2023033115534492500_","first-page":"35","article-title":"Non-adherence to topical treatments for actinic keratosis","volume":"8","author":"Shergill","year":"2013","journal-title":"Patient Prefer Adherence"},{"issue":"Suppl. 1","key":"2023033115534492500_","first-page":"AB153","article-title":"Local skin responses associated with ingenol mebutate gel for the treatment of actinic keratosis: two analyses of pooled data","volume":"66","author":"Lebwohl","year":"2012","journal-title":"J Am Acad Dermatol"},{"key":"2023033115534492500_","first-page":"154","article-title":"Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results","volume":"13","author":"Berman","year":"2014","journal-title":"J Drugs Dermatol"},{"key":"2023033115534492500_","first-page":"741","article-title":"Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results","volume":"13","author":"Berman","year":"2014","journal-title":"J Drugs Dermatol"},{"issue":"Suppl. 3","key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1365-2133.2007.07857.x","article-title":"Low prevalence of p53, p16(INK4a) and Ha-ras tumour-specific mutations in low-graded actinic keratosis","volume":"156","author":"Nindl","year":"2007","journal-title":"Br J Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1471-2407-13-58","article-title":"Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients","volume":"13","author":"Hameetman","year":"2013","journal-title":"BMC Cancer"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/archdermatol.2009.378","article-title":"Gene expression patterns of normal human skin, actinic keratosis, and squamous cell carcinoma: a spectrum of disease progression","volume":"146","author":"Padilla","year":"2010","journal-title":"Arch Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jaad.2011.02.011","article-title":"Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model","volume":"66","author":"Zalaudek","year":"2012","journal-title":"J Am Acad Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2147\/CCID.S28905","article-title":"New developments in the treatment of actinic keratosis: focus on ingenol mebutate gel","volume":"5","author":"Berman","year":"2012","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.jaad.2010.12.038","article-title":"Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesion-specific immune response","volume":"66","author":"Rosen","year":"2012","journal-title":"J Am Acad Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/jid.2011.418","article-title":"Ingenol mebutate field-directed treatment of UVB-damaged skin reduces lesion formation and removes mutant p53 patches","volume":"132","author":"Cozzi","year":"2012","journal-title":"J Invest Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00403-012-1270-0","article-title":"Effective treatment of squamous cell carcinomas with ingenol mebutate gel in immunologically intact SKH1 mice","volume":"305","author":"Cozzi","year":"2013","journal-title":"Arch Dermatol Res"},{"volume-title":"Ingenol mebutate gel 500 mcg\/g (0.05%) is efficacious in treating subclinical actinic keratoses in a field with cancerisation \u2013 assessment by reflectance confocal microscopy. Presented at the 22nd EADV Congress","year":"2013","author":"Ulrich","key":"2023033115534492500_"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1001\/jamadermatol.2015.0502","article-title":"Long-term efficacy of topical fluorouracil cream, 5%, for treating actinic keratosis: a randomized clinical trial","volume":"151","author":"Pomerantz","year":"2015","journal-title":"JAMA Dermatol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1111\/jdv.13063","article-title":"Evaluation of the tolerability and safety of a 0.015% ingenol mebutate gel compared to 5% 5-fluorouracil cream for the treatment of facial actinic keratosis: a prospective randomized trial","volume":"29","author":"Samorano","year":"2015","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"e96829","DOI":"10.1371\/journal.pone.0096829","article-title":"A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe","volume":"9","author":"Vegter","year":"2014","journal-title":"PLoS One"},{"key":"2023033115534492500_","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1067\/mjd.2002.126257","article-title":"Cycle therapy of actinic keratoses of the face and scalp with 5% topical imiquimod cream: an open-label trial","volume":"47","author":"Salasche","year":"2002","journal-title":"J Am Acad Dermatol"},{"key":"2023033115534492500_","first-page":"1353","article-title":"Treatment of facial actinic keratoses with aminolevulinic acid photodynamic therapy (ALA-PDT) or ingenol mebutate 0.015% gel with and without prior treatment with ALA-PDT","volume":"13","author":"Berman","year":"2014","journal-title":"J Drugs Dermatol"},{"key":"2023033115534492500_","first-page":"19","article-title":"Tolerability and pharmacokinetics of ingenol mebutate 0.05% gel applied to treatment areas up to 100 cm2 on the forearm(s) of patients with actinic keratosis","volume":"7","author":"Anderson","year":"2014","journal-title":"J Clin Aesthet Dermatol"}],"container-title":["British Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjd.14222","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/174\/3\/505\/49716309\/bjd0505.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/174\/3\/505\/49716309\/bjd0505.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:54:50Z","timestamp":1692100490000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjd\/article\/174\/3\/505\/6617147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,1]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3,1]]},"published-print":{"date-parts":[[2016,3,1]]}},"URL":"https:\/\/doi.org\/10.1111\/bjd.14222","relation":{},"ISSN":["1365-2133","0007-0963"],"issn-type":[{"type":"electronic","value":"1365-2133"},{"type":"print","value":"0007-0963"}],"subject":[],"published-other":{"date-parts":[[2016,3,1]]},"published":{"date-parts":[[2016,3,1]]}}}