{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:05:36Z","timestamp":1791165936920,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70112351"],"award-info":[{"award-number":["70112351"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Photodynamic therapy (<jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content>) is a highly effective treatment option for patients with actinic keratoses (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>). However, efficacy can be reduced by insufficient illumination or hyperkeratotic nature of lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate if <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> combined with a topical intervention is superior to monotherapy in terms of efficacy and tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic literature research was conducted in Medline, Embase and <jats:styled-content style=\"fixed-case\">CENTRAL<\/jats:styled-content>. Pertinent trial registers were hand\u2010searched for eligible randomized controlled trials (<jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s) until 20 August 2018. Results were pooled using a random effects model to calculate relative risks (<jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content>) or mean differences. The risk of bias was assessed with the Cochrane Risk of Bias Tool. The quality of evidence was estimated for each outcome of interest according to <jats:styled-content style=\"fixed-case\">GRADE<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Out of 1800 references initially identified, 10 <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s with a total sample size of <jats:italic>n<\/jats:italic>\u00a0=\u00a0277 were included. Four studies investigated a combination of <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> with imiquimod cream, three with 5\u2010fluorouracil cream and one each with ingenol mebutate gel, tazarotene gel and calcipotriol ointment, respectively. Patients treated with a combination showed higher participant complete (<jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content> 1.63; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.15\u20102.33; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.007) and partial clearance rates (<jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content> 1.19; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 0.84\u20131.67; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.33). Similarly, the lesion\u2010specific clearance was higher for <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> plus topical intervention compared to monotherapy (<jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content> 1.48; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.04\u20132.11; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03). A subgroup analysis was performed for <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> combined with imiquimod, revealing an increased participant complete clearance rate compared to monotherapy (<jats:styled-content style=\"fixed-case\">RR<\/jats:styled-content> 1.57, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.09\u20132.25, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content>\u2010induced pain and local skin reactions after treatment were poorly reported. The studies were estimated at high risk for performance and detection bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of <jats:styled-content style=\"fixed-case\">PDT<\/jats:styled-content> with another topical drug intervention does improve <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> clearance rates compared to either monotherapy alone. This study highlights that the sequential application of two field\u2010directed treatments represents an efficient approach in patients with multiple <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> and field cancerization.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15459","type":"journal-article","created":{"date-parts":[[2019,2,2]],"date-time":"2019-02-02T02:19:35Z","timestamp":1549073975000},"page":"863-873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Efficacy of photodynamic therapy combined with topical interventions for the treatment of actinic keratosis: a meta\u2010analysis"],"prefix":"10.1111","volume":"33","author":[{"given":"M.V.","family":"Heppt","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Steeb","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Leiter","sequence":"additional","affiliation":[{"name":"Department of Dermatology Center for Dermatooncology University Hospital T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Berking","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.103342"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.103343"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24284"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13180"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14375"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2006.06.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08882.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15185"},{"key":"e_1_2_6_10_1","first-page":"e123","article-title":"Preferred reporting items for systematic reviews and meta\u2010analyses: the PRISMA Statement","volume":"3","author":"Moher D","year":"2009","journal-title":"Open Med"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470712184"},{"key":"e_1_2_6_12_1","unstructured":"Review Manager (RevMan) [Computer program]. 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