{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:50:42Z","timestamp":1792842642115,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T00:00:00Z","timestamp":1534204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Biofrontera Bioscience GmbH"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The most effective treatment modality for actinic keratosis (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>) is photodynamic therapy (<jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content>). Major obstacles of <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high\u2010power light source with natural daylight for more extended illumination at lower light doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether <jats:styled-content style=\"fixed-case\">BF<\/jats:styled-content>\u2010200 <jats:styled-content style=\"fixed-case\">ALA<\/jats:styled-content> (a nanoemulsion gel containing 7.8% 5\u2010aminolaevulinic acid) is non\u2010inferior to <jats:styled-content style=\"fixed-case\">MAL<\/jats:styled-content> (a cream containing 16% methyl\u2010aminolaevulinate) in the treatment of mild\u2010to\u2010moderate <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> with daylight <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">dPDT<\/jats:styled-content>). Non\u2010inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content>) is established if the mean response for <jats:styled-content style=\"fixed-case\">BF<\/jats:styled-content>\u2010200 <jats:styled-content style=\"fixed-case\">ALA<\/jats:styled-content> is no worse than for <jats:styled-content style=\"fixed-case\">MAL<\/jats:styled-content>, within a statistical margin of \u0394 = \u221212.5%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1\u2010year follow\u2010up results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve weeks after a single <jats:styled-content style=\"fixed-case\">dPDT<\/jats:styled-content>, 79.8% of the <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> lesions treated with <jats:styled-content style=\"fixed-case\">BF<\/jats:styled-content>\u2010200 <jats:styled-content style=\"fixed-case\">ALA<\/jats:styled-content> gel and 76.5% of the lesions treated with <jats:styled-content style=\"fixed-case\">MAL<\/jats:styled-content> cream were completely cleared. The median of differences was 0.0 with a one\u2010sided 97.5% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> of 0.0, establishing non\u2010inferiority (<jats:italic>P<\/jats:italic> &lt; 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with <jats:styled-content style=\"fixed-case\">BF<\/jats:styled-content>\u2010200 <jats:styled-content style=\"fixed-case\">ALA<\/jats:styled-content> and 31.6% for lesions treated with <jats:styled-content style=\"fixed-case\">MAL<\/jats:styled-content>. Adverse reactions including pain were mostly mild and transient and identical to those previously described for <jats:styled-content style=\"fixed-case\">dPDT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Daylight <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> with <jats:styled-content style=\"fixed-case\">BF<\/jats:styled-content>\u2010200 <jats:styled-content style=\"fixed-case\">ALA<\/jats:styled-content> is well\u2010tolerated and non\u2010inferior to <jats:styled-content style=\"fixed-case\">MAL<\/jats:styled-content>\/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow\u2010up.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15185","type":"journal-article","created":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T09:39:39Z","timestamp":1531993179000},"page":"288-297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["A randomized, intraindividual, non\u2010inferiority, Phase <scp>III<\/scp> study comparing daylight photodynamic therapy with <scp>BF<\/scp>\u2010200 <scp>ALA<\/scp> gel and <scp>MAL<\/scp> cream for the treatment of actinic keratosis"],"prefix":"10.1111","volume":"33","author":[{"given":"T.","family":"Dirschka","sequence":"first","affiliation":[{"name":"CentroDerm GmbH Wuppertal Germany"},{"name":"Faculty of Health University Witten\/Herdecke Witten Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ekanayake\u2010Bohlig","sequence":"additional","affiliation":[{"name":"MensingDerma Research GmbH Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Dominicus","sequence":"additional","affiliation":[{"name":"ProDerma D\u00fclmen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Aschoff","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Herrera\u2010Ceballos","sequence":"additional","affiliation":[{"name":"Department of Dermatology Hospital Clinico Virgen de la Victoria Malaga Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Botella\u2010Estrada","sequence":"additional","affiliation":[{"name":"University of Valencia Valencia Spain"},{"name":"Department of Dermatology Hospital Universitari i Polit\u00e9cnic la Fe Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hunfeld","sequence":"additional","affiliation":[{"name":"Biofrontera Bioscience GmbH Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kremser","sequence":"additional","affiliation":[{"name":"Biofrontera Bioscience GmbH Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Biofrontera Bioscience GmbH Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"L\u00fcbbert","sequence":"additional","affiliation":[{"name":"Biofrontera Bioscience GmbH Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Puig","sequence":"additional","affiliation":[{"name":"Hospital Clinic de Barcelona Barcelona Spain"},{"name":"University of Barcelona Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12031"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1994.tb08544.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04432.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08450.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13420"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13326"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13138"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13228"},{"key":"e_1_2_6_10_1","first-page":"282","article-title":"Switching From Conventional Photodynamic Therapy to Daylight Photodynamic Therapy For Actinic Keratoses: Systematic Review and Meta\u2010analysis","volume":"108","author":"Tomas\u2010Velazquez A","year":"2017","journal-title":"Actas Dermosifiliogr"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10613.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-012-0777-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/1011-1344(90)85083-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2345"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(91)70113-G"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14498"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12158"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.103344"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08267.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.09873.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09119.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0781.2011.00611.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12354"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2015.2570"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2015.06.001"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366548"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10833.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.11200.x"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdv.15185","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.15185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T18:50:26Z","timestamp":1694717426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.15185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,14]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/jdv.15185"],"URL":"https:\/\/doi.org\/10.1111\/jdv.15185","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,14]]},"assertion":[{"value":"2018-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}