{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:59:24Z","timestamp":1773982764657,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Legacy Healthcare"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alopecia areata (AA) is a debilitating autoimmune-mediated disorder marked by nonscarring hair loss. It significantly impairs patients\u2019 quality of life (QoL). Inflammation and immune dysregulation, especially involving chemokines like interleukin-8 and Janus kinase (JAK)-dependent signalling pathways, underlie AA pathogenesis. As oral JAK inhibitors are approved for severe cases only, unmet needs persist, particularly for paediatric patients and those with moderate AA. Cinainu, a topical solution containing four botanical extracts, may address these gaps due to its anti-inflammatory, anti-apoptotic and antioxidant properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This phase II\/III study evaluated the efficacy and safety of Cinainu in children and adolescents with moderate-to-severe AA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The RAAINBOW study, an international, double-blind, placebo-controlled trial, involved 107 paediatric patients randomly assigned (2 : 1) to receive Cinainu or placebo for 24 weeks, followed by a 24-week untreated follow-up period. The primary analysis included 62 patients meeting predefined criteria for moderate-to-severe AA. The primary endpoint was the relative change in Severity of Alopecia Tool (SALT) score from baseline to Week 24. Secondary outcomes included responder rate (\u2265 40% improvement in SALT score from baseline to Week 24), absolute SALT score changes, and QoL improvements measured by the Children\u2019s Dermatology Life Quality Index (CDLQI) and EuroQol Visual Analogue Scale (EQ-VAS). Safety assessments included treatment-emergent adverse events. This trial is registered with EudraCT: 2016-003208-30 and ClinicalTrials.gov: NCT03240627.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cinainu showed significant benefits compared with placebo in relative change in SALT score from baseline to Week 24: adjusted mean difference [95% confidence interval CI)] + 26.3% (0.1\u201352.5); P = 0.0488, Cohen\u2019s d = 0.52. A significantly higher proportion of Cinainu-treated patients met responder criteria at Week 24 (26.2% vs. 5.0%; P = 0.0484). Cinainu also led to significant QoL improvements at Week 24, with effect sizes of d = 0.61 in CDLQI and d = 0.69 in EQ-VAS. Benefits were sustained during the follow-up period: adjusted mean difference (95% CI) + 39.4% (13.1\u201365.6); P = 0.0033, Cohen\u2019s d = 0.80, in relative change in SALT score from baseline to Week 48 and large effect sizes in CDLQI (d = 0.79). No serious adverse events were related to Cinainu, and treatment was well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, Cinainu showed efficacy, safety and sustained benefits during follow-up in children and adolescents with moderate-to-severe AA, a population with significant unmet needs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf279","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T19:09:30Z","timestamp":1752692970000},"page":"37-46","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of Cinainu in paediatric alopecia areata: an international, double-blind, randomized, placebo-controlled, phase II\/III trial"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3528-3752","authenticated-orcid":false,"given":"Ulrike","family":"Blume-Peytavi","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology, Clinical Research Center for Hair and Skin Science, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Maria","family":"Piraccini","sequence":"additional","affiliation":[{"name":"Dermatology Unit \u2013 IRCCS Azienda Ospedaliero-Universitaria di Bologna , Emilia-Romagna ,","place":["Italy"]},{"name":"Department of Experimental, Diagnostic and Specialty Medicine Alma Mater Studiorum, University of Bologna , Emilia-Romagna ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Reygagne","sequence":"additional","affiliation":[{"name":"Sabouraud Center, Saint-Louis Hospital , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-7949","authenticated-orcid":false,"given":"Julien","family":"Guiraud","sequence":"additional","affiliation":[{"name":"Vergio , Clichy ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhaswati","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"MusigmaDelta Consultancy Private Limited , Bangalore ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Guichard","sequence":"additional","affiliation":[{"name":"Legacy Healthcare , Epalinges ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Liu","sequence":"additional","affiliation":[{"name":"Legacy Healthcare , Epalinges ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Pralong","sequence":"additional","affiliation":[{"name":"Legacy Healthcare , Epalinges ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Harti","sequence":"additional","affiliation":[{"name":"Legacy Healthcare , Epalinges ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"2026010607280430000_ljaf279-B1","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1093\/bjd\/ljae307","article-title":"Lifetime incidence and healthcare disparities in alopecia areata: a UK population-based cohort study","volume":"191","author":"Thompson","year":"2024","journal-title":"Br J Dermatol"},{"key":"2026010607280430000_ljaf279-B2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/bjd.20628","article-title":"The epidemiology of alopecia areata: a population-based cohort study in UK primary care","volume":"186","author":"Harries","year":"2022","journal-title":"Br J Dermatol"},{"key":"2026010607280430000_ljaf279-B3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/ajd.12941","article-title":"Treatment of alopecia areata: an Australian expert consensus statement","volume":"60","author":"Cranwell","year":"2019","journal-title":"Australas J Dermatol"},{"key":"2026010607280430000_ljaf279-B4","first-page":"397","article-title":"Epidemiology and burden of alopecia areata: a systematic review","volume":"8","author":"Villasante Fricke","year":"2015","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"2026010607280430000_ljaf279-B5","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.18848","article-title":"Quality of life in children and adolescents with alopecia areata \u2013 a systematic review","author":"Prendke","year":"2023","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2026010607280430000_ljaf279-B6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/bjd.21055","article-title":"The associated burden of mental health conditions in alopecia areata: a population-based study in UK primary care","volume":"187","author":"Macbeth","year":"2022","journal-title":"Br J Dermatol"},{"key":"2026010607280430000_ljaf279-B7","doi-asserted-by":"crossref","first-page":"145","DOI":"10.5694\/mja13.10895","article-title":"Alopecia areata and suicide of children","volume":"200","author":"Sinclair","year":"2014","journal-title":"Med J Aust"},{"key":"2026010607280430000_ljaf279-B8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1159\/000466704","article-title":"Bullying and quality of life in pediatric alopecia areata","volume":"3","author":"Christensen","year":"2017","journal-title":"Skin Appendage Disord"},{"key":"2026010607280430000_ljaf279-B9","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/jocd.14122","article-title":"Psychiatric basics of alopecia areata in pediatric patients: evaluation of emotion dysregulation, somatization, depression, and anxiety levels","volume":"21","author":"Altunisik","year":"2022","journal-title":"J Cosmet Dermatol"},{"key":"2026010607280430000_ljaf279-B10","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.jaad.2023.05.049","article-title":"Janus kinase inhibitors for alopecia areata","volume":"89","author":"King","year":"2023","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.4103\/ijt.ijt_80_18","article-title":"Serum interleukin-15 is a marker of alopecia areata severity","volume":"11","author":"Ebrahim","year":"2019","journal-title":"Int J Trichol"},{"key":"2026010607280430000_ljaf279-B12","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1365-2230.2009.03523.x","article-title":"Serum T helper 1 cytokine levels are greater in patients with alopecia areata regardless of severity or atopy","volume":"35","author":"Barahmani","year":"2010","journal-title":"Clin Exp Dermatol"},{"key":"2026010607280430000_ljaf279-B13","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1365-2133.2007.07943.x","article-title":"Serum chemokine profiles in patients with alopecia areata","volume":"157","author":"Kuwano","year":"2007","journal-title":"Br J Dermatol"},{"key":"2026010607280430000_ljaf279-B14","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jaad.2020.04.138","article-title":"Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation","volume":"84","author":"Glickman","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B15","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1126\/science.2648569","article-title":"The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes","volume":"243","author":"Larsen","year":"1989","journal-title":"Science"},{"key":"2026010607280430000_ljaf279-B16","doi-asserted-by":"crossref","first-page":"155828","DOI":"10.1016\/j.cyto.2022.155828","article-title":"Interleukin-8: an evolving chemokine","volume":"153","author":"Matsushima","year":"2022","journal-title":"Cytokine"},{"key":"2026010607280430000_ljaf279-B17","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.3645","article-title":"Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition","volume":"20","author":"Xing","year":"2014","journal-title":"Nat Med"},{"key":"2026010607280430000_ljaf279-B18","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1056\/NEJMoa2110343","article-title":"Two phase 3 trials of baricitinib for alopecia areata","volume":"386","author":"King","year":"2022","journal-title":"N Engl J Med"},{"key":"2026010607280430000_ljaf279-B19","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.jaad.2024.06.097","article-title":"Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: results from the phase 3 randomized, controlled trial (THRIVE-AA1)","volume":"91","author":"King","year":"2024","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B20","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/S0140-6736(23)00222-2","article-title":"Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial","volume":"401","author":"King","year":"2023","journal-title":"Lancet"},{"key":"2026010607280430000_ljaf279-B21","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1001\/jamadermatol.2024.2734","article-title":"Baricitinib withdrawal and \u00adretreatment in patients with severe alopecia areata: the BRAVE-AA1 randomized clinical trial","volume":"160","author":"King","year":"2024","journal-title":"JAMA Dermatol"},{"key":"2026010607280430000_ljaf279-B22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jdrv.2024.11.008","article-title":"Patient preferences in the treatment of alopecia areata: a review of the literature","volume":"3","author":"Carmichael","year":"2025","journal-title":"JAAD Rev"},{"key":"2026010607280430000_ljaf279-B23","doi-asserted-by":"crossref","first-page":"689044","DOI":"10.3389\/fimmu.2021.689044","article-title":"Potential implications of quercetin in autoimmune diseases","volume":"12","author":"Shen","year":"2021","journal-title":"Front Immunol"},{"key":"2026010607280430000_ljaf279-B24","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/13880209.2021.1874028","article-title":"A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents","volume":"59","author":"Marefati","year":"2021","journal-title":"Pharmaceut Biol"},{"key":"2026010607280430000_ljaf279-B25","first-page":"123","article-title":"Cellium\u00ae GC: evaluation of a new natural active ingredient in 210\u2005mg\/ml topical solution, through scalp biopsy","volume":"3","author":"Cuc\u00e9","year":"2011","journal-title":"Surg Cosmet Dermatol"},{"key":"2026010607280430000_ljaf279-B26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1515\/chem-2017-0021","article-title":"Antimicrobial activity and thiosulfinates profile of a formulation based on Allium cepa L. extract","volume":"15","author":"Orasan","year":"2017","journal-title":"Open Chemistry"},{"key":"2026010607280430000_ljaf279-B27","doi-asserted-by":"crossref","first-page":"AB132","DOI":"10.1016\/j.jaad.2016.02.519","article-title":"A topical botanical lotion increases and remodels scalp collagen content through longer anagen phase, opening new perspectives","volume":"74","author":"Liu","year":"2016","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B28","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000480024","article-title":"Efficacy and safety of a topical botanical in female androgenetic alopecia: a randomized, single-blinded, vehicle-controlled study","volume":"4","author":"Katoulis","year":"2018","journal-title":"Skin Appendage Disord"},{"key":"2026010607280430000_ljaf279-B29","first-page":"1829","article-title":"Impact of a topical lotion, CG428, on permanent chemotherapy-induced alopecia in breast cancer survivors: a pilot randomized double-blind controlled clinical trial (VOLUME RCT)","volume":"28","author":"Kang","year":"2020","journal-title":"Support Care Cancer"},{"key":"2026010607280430000_ljaf279-B30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/jidsymp.2015.45","article-title":"Development of uniform protocol for alopecia areata clinical trials","volume":"17","author":"Solomon","year":"2015","journal-title":"J Investig Dermatol Symp Proc"},{"key":"2026010607280430000_ljaf279-B31","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.jaad.2003.09.032","article-title":"Alopecia areata investigational assessment guidelines \u2013 part II. National Alopecia Areata Foundation","volume":"51","author":"Olsen","year":"2004","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B32","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1111\/j.1365-2133.1995.tb16953.x","article-title":"The Children\u2019s Dermatology Life Quality Index (CDLQI): initial validation and practical use","volume":"132","author":"Lewis-Jones","year":"2010","journal-title":"Br J Dermatol"},{"key":"2026010607280430000_ljaf279-B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2025.03.020","article-title":"Head-to-head comparisons of the distributional characteristics and measurement properties of the 3-level and 5-level versions of the EQ-5D-Y: a systematic review","author":"Cheng","year":"2025","journal-title":"Value Health"},{"key":"2026010607280430000_ljaf279-B34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1346-8138.2011.01476.x","article-title":"Advances in the management of alopecia areata","volume":"39","author":"Ito","year":"2012","journal-title":"J Dermatol"},{"key":"2026010607280430000_ljaf279-B35","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jaad.2006.05.008","article-title":"Alopecia areata: a long term follow-up study of 191 patients","volume":"55","author":"Tosti","year":"2006","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B36","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/j.1365-2133.2012.10955.x","article-title":"British Association of Dermatologists\u2019 guidelines for the management of alopecia areata 2012","volume":"166","author":"Messenger","year":"2012","journal-title":"Br J Dermatol"},{"key":"2026010607280430000_ljaf279-B37","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1111\/acer.14670","article-title":"Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: a meta-regression analysis to develop an enrichment strategy","volume":"45","author":"Scherrer","year":"2021","journal-title":"Alcohol Clin Exp Res"},{"key":"2026010607280430000_ljaf279-B38","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.jaad.2021.04.077","article-title":"Treatment of pediatric alopecia areata: a systematic review","volume":"86","author":"Barton","year":"2022","journal-title":"J Am Acad Dermatol"},{"key":"2026010607280430000_ljaf279-B39","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s13555-023-00892-5","article-title":"A review on the safety of using JAK inhibitors in dermatology: clinical and laboratory monitoring","volume":"13","author":"Samuel","year":"2023","journal-title":"Dermatol Ther (Heidelb)"},{"key":"2026010607280430000_ljaf279-B40","author":"European Medicines Agency"},{"key":"2026010607280430000_ljaf279-B41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jaad.2021.08.043","article-title":"Development of the alopecia areata scale for clinical use: results of an academic-industry collaborative effort","volume":"86","author":"King","year":"2022","journal-title":"J Am Acad Dermatol"}],"container-title":["British Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjd\/advance-article-pdf\/doi\/10.1093\/bjd\/ljaf279\/63779555\/ljaf279.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/194\/1\/37\/63779555\/ljaf279.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/194\/1\/37\/63779555\/ljaf279.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:28:15Z","timestamp":1767702495000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjd\/article\/194\/1\/37\/8203556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,7,16]]},"published-print":{"date-parts":[[2026,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/bjd\/ljaf279","relation":{},"ISSN":["0007-0963","1365-2133"],"issn-type":[{"value":"0007-0963","type":"print"},{"value":"1365-2133","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,7,16]]}}}