{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:19:12Z","timestamp":1790957952985,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,5,18]],"date-time":"2016-05-18T00:00:00Z","timestamp":1463529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anacor Pharmaceuticals, Palo Alto, California"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Dermatology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phosphodiesterase\u20104 (PDE4) is a promising target in atopic dermatitis (AD) treatment. The pharmacokinetics (PK), safety, and efficacy of crisaborole topical ointment, 2% (formerly AN2728) (Anacor Pharmaceuticals, Palo Alto, CA), a boron\u2010based benzoxaborole PDE4 inhibitor, were evaluated in children with mild to moderate AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 1b, open\u2010label, maximal\u2010use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg\/cm<jats:sup>2<\/jats:sup>) for 28 days enrolled patients ages 2 to 17 years with extensive AD involving 25% or more or 35% or more treatable body surface area, depending on age. Primary PK and safety assessments included systemic exposure to crisaborole and its metabolites after 7 days of treatment and the incidence of treatment\u2010emergent adverse events (TEAEs). Secondary efficacy assessments included change from baseline in Investigator Static Global Assessment (ISGA), treatment success (ISGA score \u22641 with a two\u2010grade or greater improvement from baseline), and improvement in five AD signs and symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 34 patients enrolled, 31 completed the study. Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8. Twenty\u2010three of 34 patients reported one or more TEAEs; 95% were mild or moderate and one patient discontinued because of a TEAE. Mean ISGA scores declined from 2.65 at baseline to 1.15 at day 29, 47.1% of patients achieved treatment success, and 64.7% of patients achieved ISGA scores of clear (0) or almost clear <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"#pde12872-bib-0001\"\/>. Mean severity scores for AD signs and symptoms declined throughout the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This open\u2010label study provides evidence that crisaborole topical ointment, 2% was well tolerated, with limited systemic exposure under maximal\u2010use conditions in patients ages 2 years and older.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pde.12872","type":"journal-article","created":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T12:24:15Z","timestamp":1463660655000},"page":"380-387","source":"Crossref","is-referenced-by-count":75,"title":["Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open\u2010Label, Maximal\u2010Use Systemic Exposure Study"],"prefix":"10.1111","volume":"33","author":[{"given":"Lee T.","family":"Zane","sequence":"first","affiliation":[{"name":"Anacor Pharmaceuticals Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Kircik","sequence":"additional","affiliation":[{"name":"DermResearch Louisville Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Call","sequence":"additional","affiliation":[{"name":"St. Louis University St Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Tschen","sequence":"additional","affiliation":[{"name":"Academic Dermatology Associates Albuquerque New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe Diana","family":"Draelos","sequence":"additional","affiliation":[{"name":"Dermatology Consulting Services High Point North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Chanda","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrie","family":"Van Syoc","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelaide A.","family":"Hebert","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra074081"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.03.023"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.2005.22303.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.03.030"},{"key":"e_1_2_9_6_1","first-page":"364","article-title":"Therapeutic benefit of PDE4 inhibitors in inflammatory diseases","volume":"8","author":"Dastidar SG","year":"2007","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152807780077318"},{"key":"e_1_2_9_8_1","first-page":"495","article-title":"Is PDE4 too difficult a drug target?","volume":"11","author":"Higgs G","year":"2010","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.03.007"},{"key":"e_1_2_9_10_1","first-page":"1236","article-title":"AN\u20102728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis","volume":"10","author":"Nazarian R","year":"2009","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/11319300-000000000-00000"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-013-0013-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.105.4.794"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2005.01.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.07.058"},{"key":"e_1_2_9_16_1","unstructured":"ZaneLT TomWL ChandaSet al.Safety pharmacokinetics and efficacy of AN2728 ointment 2% in a phase 2 study of adolescents with mild\u2010to\u2010moderate atopic dermatitis. Poster presented at the International Investigative Dermatology Meeting Edinburgh Scotland May 8\u201311 2013."},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2340\/00015555924447","article-title":"Diagnostic features of atopic dermatitis","volume":"60","author":"Hanifin JM","year":"1980","journal-title":"Acta Derm Venereol Suppl (Stockh)"}],"container-title":["Pediatric Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpde.12872","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pde.12872","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pde.12872","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pde.12872","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T15:43:35Z","timestamp":1695743015000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pde.12872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,18]]},"references-count":16,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1111\/pde.12872"],"URL":"https:\/\/doi.org\/10.1111\/pde.12872","archive":["Portico"],"relation":{},"ISSN":["0736-8046","1525-1470"],"issn-type":[{"value":"0736-8046","type":"print"},{"value":"1525-1470","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,18]]}}}