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Subsequent <jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content> samples were taken as close as possible to the previously biopsied site at week 4 and week 16. After sampling, biopsies were split; one half was processed for <jats:italic>in\u00a0vivo <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> analysis using real\u2010time quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>; the other half was cultured for <jats:italic>ex\u00a0vivo<\/jats:italic> protein analysis using a proximity extension assay (Olink). Linear mixed effects models were calculated to compare the levels of inflammatory markers in <jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content> skin between apremilast and placebo over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, 17 proteins with a fold change &gt;2 in <jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content> vs. <jats:styled-content style=\"fixed-case\">HSN<\/jats:styled-content> skin were identified in 20 patients. The top five were <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A (5), S100A12, <jats:styled-content style=\"fixed-case\">CST<\/jats:styled-content>5, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201012\/23p40, CD6 (1) with fold changes ranging from 6.6 to 1638, respectively (FDR &lt;0.044). Linear mixed effects models for 75 assays were calculated. Protein levels of S100A12 decreased during treatment in the apremilast group compared with the placebo group (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.014, <jats:styled-content style=\"fixed-case\">FDR<\/jats:styled-content>\u00a0=\u00a00.186). None of the 14 genes exhibited significant changes in expression over time. However, an evident downward trend in relative <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017F was demonstrated in patients receiving apremilast.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We did not detect statistically significant changes in inflammatory markers in <jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content> skin of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> patients receiving apremilast compared with placebo, despite clinical improvement in the apremilast group. Nonetheless, S100A12 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A were significantly elevated in <jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content> skin and showed a decrease in response to apremilast. The translational model in clinical trials involving <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> clearly needs further improvement.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15354","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T12:51:40Z","timestamp":1542631900000},"page":"761-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Apremilast for moderate hidradenitis suppurativa: no significant change in lesional skin inflammatory biomarkers"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1448-5972","authenticated-orcid":false,"given":"A.R.J.V.","family":"Vossen","sequence":"first","affiliation":[{"name":"Department of Dermatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.H.","family":"van der Zee","sequence":"additional","affiliation":[{"name":"Department of Dermatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Davelaar","sequence":"additional","affiliation":[{"name":"Laboratory of Rheumatology &amp; Dermatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.M.C.","family":"Mus","sequence":"additional","affiliation":[{"name":"Laboratory of Rheumatology &amp; Dermatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.B.A.","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Dermatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.P.","family":"Prens","sequence":"additional","affiliation":[{"name":"Department of Dermatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15233"},{"key":"e_1_2_6_3_1","first-page":"32202","article-title":"Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial","author":"Vossen ARJV","year":"2018","journal-title":"J Am Acad Dermatol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199902)187:3<358::AID-PATH253>3.0.CO;2-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004030100219"},{"key":"e_1_2_6_6_1","first-page":"71","article-title":"An improvement of the 2^(\u2010delta delta CT) method for quantitative real\u2010time polymerase chain reaction data analysis","volume":"3","author":"Rao X","year":"2013","journal-title":"Biostat Bioinforma Biomath"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.22719.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13269"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14214"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12234"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxr110"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2007.06.001"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40099"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.05.039"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh299"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10643.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14338"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2016.08.036"}],"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.15354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.15354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jdv.15354","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.15354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T02:48:20Z","timestamp":1694227700000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.15354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,10]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/jdv.15354"],"URL":"https:\/\/doi.org\/10.1111\/jdv.15354","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,10]]},"assertion":[{"value":"2018-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}