{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:29:09Z","timestamp":1790126949337,"version":"4.0.1"},"reference-count":104,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["12\/186\/01"],"award-info":[{"award-number":["12\/186\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title>\n<jats:p>Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant\/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-2\"><jats:title>Primary objective<\/jats:title>\n<jats:p>Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title>\n<jats:p>Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title>\n<jats:p>UK secondary care dermatology outpatient clinics.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title>\n<jats:p>Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-6\"><jats:title>Primary end point<\/jats:title>\n<jats:p>Natural logarithm of the Hand Eczema Severity Index\u2005+\u20051, 12 weeks post planned start of treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-7\"><jats:title>Randomisation<\/jats:title>\n<jats:p>Participants randomised 1\u00a0:\u00a01 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-8\"><jats:title>Blinding<\/jats:title>\n<jats:p>Blinded primary end-point assessor.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-9\"><jats:title>Results<\/jats:title>\n<jats:p>Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-10\"><jats:title>Primary outcome<\/jats:title>\n<jats:p>The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10\u201370%) of that at baseline for alitretinoin compared with 50% (20\u2013100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval)\u2005=\u20050.66 (0.52 to 0.82), <jats:italic>p<\/jats:italic>\u2005=\u20050.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-11\"><jats:title>Primary analysis results were consistent for secondary end points<\/jats:title>\n<jats:p>Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear\/almost clear assessment during the trial period.<\/jats:p>\n<jats:p>Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (\u2265\u00a080% received, no treatment breaks\u2005&gt;\u20057 days during first 12 weeks). High levels of missing data were observed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-12\"><jats:title>Safety<\/jats:title>\n<jats:p>One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-13\"><jats:title>Conclusion<\/jats:title>\n<jats:p>As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points.<\/jats:p>\n<jats:p>Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty.<\/jats:p>\n<jats:p>Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-14\"><jats:title>Limitations<\/jats:title>\n<jats:p>Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-15\"><jats:title>Further work<\/jats:title>\n<jats:p>Further analysis of substudies and pilot data will provide valuable information for future studies.<\/jats:p>\n<jats:p>A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-16\"><jats:title>Trial registration<\/jats:title>\n<jats:p>This trial is registered as ISRCTN80206075.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-17\"><jats:title>Funding<\/jats:title>\n<jats:p>This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12\/186\/01) and is published in full in <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.<\/jats:p>\n<\/jats:sec>","DOI":"10.3310\/twqc0141","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T08:24:41Z","timestamp":1728030281000},"page":"1-123","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2328-4926","authenticated-orcid":true,"given":"Miriam","family":"Wittmann","sequence":"first","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, Yorkshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-1075","authenticated-orcid":true,"given":"Isabelle 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