{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:26:41Z","timestamp":1783726001291,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023331","name":"LEO Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023331","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":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic Hand Eczema (CHE) is a prevalent inflammatory skin condition characterized by pain, pruritus and significant impact on patients' quality of life. Delgocitinib cream, a pan\u2010Janus kinase inhibitor, has shown potential in targeting the key mediators of CHE. To develop a detailed trial drug safety profile, it is vital to assess systemic exposure and bioavailability following repeated drug applications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This analysis aimed to evaluate the systemic exposure and bioavailability of delgocitinib cream 20\u2009mg\/g in adults with moderate to severe CHE and compare these parameters with those from oral delgocitinib administration in healthy adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An open\u2010label, single\u2010arm, Phase 1 trial (NCT05486117) was conducted involving 16 adults with moderate to severe CHE. Participants applied delgocitinib cream 20\u2009mg\/g twice daily for 1\u2009week. Pharmacokinetic sampling was performed on Day (D)1 and D8. Systemic exposure was compared with data from two Phase 1 trials involving oral delgocitinib in healthy adults (1.5\u201312\u2009mg, NCT05050279, and 1\u2013100\u2009mg, NBX1\u20101).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Delgocitinib cream demonstrated minimal systemic exposure, with geometric mean maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) values of 0.50\u2009ng\/mL on D1 and 0.46\u2009ng\/mL on D8. The geometric mean area under the concentration\u2013time curve from 0 to 12\u2009h (AUC<jats:sub>0\u201312h<\/jats:sub>) was 2.5\u2009h*ng\/mL on D1 and 3.7\u2009h*ng\/mL on D8. No significant accumulation of delgocitinib was observed over time. Systemic exposure with topical application was significantly lower than with oral administration, with a relative bioavailability of 0.6%. Delgocitinib cream was well tolerated, with no reported adverse events during the trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Delgocitinib cream shows minimal systemic exposure and is well tolerated in patients with moderate to severe CHE. These findings suggest that no systemic pharmacological effect is expected with the application of delgocitinib cream 20\u2009mg\/g to the hands and wrists of patients with moderate to severe CHE.<\/jats:p><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link> (or equivalent) listing: NCT05486117, NCT05050279.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.20777","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:04:25Z","timestamp":1750143865000},"page":"1612-1621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Systemic exposure and bioavailability of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema"],"prefix":"10.1111","volume":"39","author":[{"given":"Diamant","family":"Tha\u00e7i","sequence":"first","affiliation":[{"name":"Institute and Comprehensive Center for Inflammation Medicine University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8926-0113","authenticated-orcid":false,"given":"Melinda","family":"Gooderham","sequence":"additional","affiliation":[{"name":"Department of Dermatology Queens University  Peterborough Ontario Canada"},{"name":"SKiN Centre for Dermatology and Probity Medical Research  Peterborough Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Lovato","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S  Ballerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Elenius","family":"Madsen","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S  Ballerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Soehoel","sequence":"additional","affiliation":[{"name":"LEO Pharma A\/S  Ballerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-6587","authenticated-orcid":false,"given":"Robert","family":"Bissonnette","sequence":"additional","affiliation":[{"name":"Innovaderm Research  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/DER.0000000000000598"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.14035"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.13459"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.12366"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.12590"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01164-5"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-014-0782-9"},{"key":"e_1_2_14_9_1","unstructured":"European Medicines Agency (EMA).Delgocitinib (Anzupgo\u00ae): Summary of Product Characteristics (SmPC).2024. Available from:https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/anzupgo\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01027-4"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.21037"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-022-00690-3"},{"key":"e_1_2_14_13_1","unstructured":"European Medicines Agency (EMA).Summary of Product Characteristics (SmPC) Opzelura. 2023. Available from:https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/opzelura\u2010epar\u2010product\u2010information_en.pdf."},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-021-00610-x"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2670"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e08938"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.20777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T10:12:31Z","timestamp":1756116751000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.20777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,17]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/jdv.20777"],"URL":"https:\/\/doi.org\/10.1111\/jdv.20777","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,17]]},"assertion":[{"value":"2025-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}