American Journal of Clinical Dermatology最新文献

{"title":"Efficacy and Safety of Tralokinumab Across Racial Subgroups in Adults with Moderate-to-Severe Atopic Dermatitis: Post Hoc Analysis of Phase III Trials","authors":"Tiffany Mayo,&nbsp;Jonathan I. Silverberg,&nbsp;April Armstrong,&nbsp;Emma Guttman-Yassky,&nbsp;Andrew Blauvelt,&nbsp;Ben Esdaile,&nbsp;Kenji Kabashima,&nbsp;Melinda Gooderham,&nbsp;Leon Kircik,&nbsp;Shannon Schneider,&nbsp;Niels Bennike,&nbsp;Rie von Eyben,&nbsp;Britta C. Martel,&nbsp;Mads A. Røpke,&nbsp;Norito Katoh,&nbsp;Andrew F. Alexis","doi":"10.1007/s40257-025-00985-1","DOIUrl":"10.1007/s40257-025-00985-1","url":null,"abstract":"<div><h3>Background</h3><p>Differences in atopic dermatitis (AD) prevalence, clinical presentation, and pathophysiology have been reported in different ethnic/racial groups; however, clinical trial data for patients with skin of color are limited. Tralokinumab is a monoclonal antibody that specifically targets interleukin-13, a key driver of AD.</p><h3>Objectives</h3><p>To investigate the efficacy and safety of tralokinumab, and examine AD biomarker expression at baseline and week 16, by self-reported racial subgroup (Asian, Black, and White) in patients with moderate-to-severe AD.</p><h3>Methods</h3><p>Post hoc analyses were conducted by racial subgroup using data from four phase 3 trials: placebo-controlled parent trials ECZTRA 1, 2, and 3 and the open-label extension trial ECZTEND. Endpoints included Investigator’s Global Assessment (IGA) 0/1, 75% improvement in Eczema Area and Severity Index (EASI-75), and adverse events. In ECZTRA 1, serum and skin samples were analyzed for biomarker expression by immunoassay and <i>Staphylococcus aureus</i> (<i>S. aureus</i>) abundance by quantitative polymerase chain reaction (qPCR).</p><h3>Results</h3><p>A total of 1876 patients pooled from ECZTRA 1/2/3 (Asian/Black/White <i>N</i> = 407/134/1335) and 1392 patients from ECZTEND (Asian/Black/White <i>N</i> = 203/108/1081) were included. Baseline characteristics were largely balanced between treatment groups and racial subgroups, although AD severity was more moderate in Black patients and regional differences were observed. At week 16 of ECZTRA 1/2/3, tralokinumab improved efficacy outcomes, including IGA 0/1 and EASI-75, relative to placebo across all subgroups. Further improvements beyond week 16 were observed with continued tralokinumab treatment, including 78%, 88%, and 83% of Asian, Black, and White patients, respectively, achieving EASI-75 at week 56 of ECZTEND (corresponding to up to 2 years total tralokinumab treatment). At baseline, serum biomarker levels were elevated in Asian patients from Japan compared with other subgroups, while Asian patients from USA/Europe had lower <i>S. aureus</i> abundance, when adjusting for IGA. The safety profile of tralokinumab was comparable to placebo, and serious adverse events and adverse events leading to treatment discontinuation were rare, across racial subgroups.</p><h3>Conclusions</h3><p>Tralokinumab was well-tolerated and improved signs, symptoms, and biomarkers in patients with moderate-to-severe AD at 16 weeks across the racial subgroups studied, with further improvement in response rates up to 2 years of treatment.</p><h3>Clinical Trial Registration</h3><p>ClinicalTrials.gov identifiers: NCT03131648 (registered 24 April 2017), NCT03160885 (registered 18 May 2017), NCT03363854 (registered 01 December 2017), and NCT03587805 (registered 03 July 2018).</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"27 1","pages":"149 - 166"},"PeriodicalIF":8.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00985-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Enthesitis in Psoriatic Disease: Insights and Implications","authors":"Rahaf Zyad Attar,&nbsp;Alice B. Gottlieb,&nbsp;Sibel Zehra Aydin","doi":"10.1007/s40257-025-00988-y","DOIUrl":"10.1007/s40257-025-00988-y","url":null,"abstract":"<div><p>Enthesitis represents a hallmark feature and central pathological process in psoriatic arthritis and has been proposed as a potential early indicator in patients with psoriasis prior to the onset of clinically apparent psoriatic arthritis. Given the risks associated with delayed diagnosis, there is growing interest in identifying at-risk patients early to enable timely interventions and personalized treatment approaches. In clinical practice, dermatologists are often the first to encounter these patients, highlighting the need for effective screening strategies in their setting. In recent years, efforts have been made to develop validated screening tools for the early detection of musculoskeletal symptoms in patients with psoriasis. Additionally, there has been a greater focus on improving assessments through imaging techniques such as ultrasound and magnetic resonance imaging. However, a universally accepted referral pathway has yet to be established, potentially creating gaps in care during the transition from psoriasis to psoriatic arthritis. This review synthesizes current evidence on the role of enthesitis in psoriatic disease, focusing on its underlying mechanisms, diagnostic approaches, and therapeutic strategies. Importantly, we propose a practical screening and referral pathway designed to support dermatologists in early recognition of at-risk patients, with the goal of facilitating timely rheumatology referral and multidisciplinary management. By emphasizing the complementary roles of questionnaires, clinical assessment, and targeted imaging, our approach aims to bridge existing gaps in care and optimize patient outcomes.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"27 1","pages":"121 - 136"},"PeriodicalIF":8.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Summary of Research: Efficacy and Safety of Delgocitinib Cream in Adults with Moderate to Severe Chronic Hand Eczema (DELTA 1 and DELTA 2): Results from Multicentre, Randomised, Controlled, Double-Blind, Phase 3 Trials","authors":"Robert Bissonnette,&nbsp;Fatima Albreiki,&nbsp;Benjamin D. Ehst,&nbsp;Anwar Al Hammadi,&nbsp;Sibylle Schliemann,&nbsp;Bin Yang,&nbsp;Jianzhong Zhang,&nbsp;Christopher G. Bunick","doi":"10.1007/s40257-025-00974-4","DOIUrl":"10.1007/s40257-025-00974-4","url":null,"abstract":"<div><p>This is a summary of the original article: “Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials”. Chronic Hand Eczema (CHE) is a heterogeneous, multifactorial, fluctuating, and chronic inflammatory disease associated with pain, itch, and a significant quality-of-life burden for patients. The phase 3 DELTA 1 and DELTA 2 trials assessed the efficacy and safety of twice-daily delgocitinib cream 20 mg/g, a pan-Janus kinase inhibitor, compared with cream vehicle in adults with moderate to severe CHE. Delgocitinib cream demonstrated superior efficacy versus cream vehicle in outcomes reported by clinicians (e.g., Investigator’s Global Assessment for CHE [IGA-CHE] treatment success [IGA-CHE 0 (clear)/1 (almost clear)] and ≥75/90% improvement in Hand Eczema Severity Index) and patients (e.g., itch, pain, and Dermatology Life Quality Index). Delgocitinib cream exhibited a favorable safety profile in both trials. These results suggest that delgocitinib cream is a treatment option for the relief of clinical signs and symptoms among patients with moderate to severe CHE for whom topical corticosteroids are inadequate or inappropriate.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"27 1","pages":"199 - 202"},"PeriodicalIF":8.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00974-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of Staging Systems for Non-head and Neck Cutaneous Squamous Cell Carcinoma","authors":"Lindsey M. Voller,&nbsp;Kelsey E. Hirotsu,&nbsp;Sumaira Z. Aasi,&nbsp;Melica Nikahd,&nbsp;Emily Ruiz,&nbsp;Nina Ran,&nbsp;Emily E. Granger,&nbsp;Shlomo Koyfman,&nbsp;Allison Vidimos,&nbsp;Ashley Wysong,&nbsp;John A. Carucci,&nbsp;Joi B. Carter,&nbsp;Javier Cañueto,&nbsp;Fabio Muradás Girardi,&nbsp;Aaron R. Mangold,&nbsp;Divya Srivastava,&nbsp;David G. Brodland,&nbsp;John A. Zitelli,&nbsp;Tyler J. Willenbrink,&nbsp;Kathryn T. Shahwan,&nbsp;David R. Carr","doi":"10.1007/s40257-025-00987-z","DOIUrl":"10.1007/s40257-025-00987-z","url":null,"abstract":"<div><h3>Background</h3><p>Data are limited regarding the performance of staging systems for non-head and neck cutaneous squamous cell carcinomas (non-HNCSCCs).</p><h3>Objective</h3><p>The aim of this study was to evaluate the performance of the Brigham and Women’s Hospital (BWH) and American Joint Committee on Cancer 8th edition (AJCC8) staging system in predicting poor outcomes in non-HNCSCCs.</p><h3>Patients and Methods</h3><p>Demographics, tumor features and stages, and outcomes for non-HNCSCCs were collected retrospectively from 11 institutions in two countries. Poor outcomes included local recurrence, metastasis, and disease-specific death; major poor outcomes excluded local recurrence. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), concordance index (<i>c</i>-index), and 3-year cumulative incidence were calculated. Cumulative incidence function (CIF) plots were created.</p><h3>Results</h3><p>9300 non-HNCSCCs were included. Ninety-five tumors (1%) resulted in major poor outcomes; 250 (2.7%) resulted in poor outcomes. The rate of local recurrence was 1.9%, and the rate of nodal metastasis was 0.74%. Major poor outcomes were predicted with sensitivities 0.48/0.49, specificities 0.98/0.96, PPVs 0.17/0.13, NPVs 0.99/0.99, and <i>c</i>-indices 0.73/0.74 for BWH/AJCC8. Poor outcomes were predicted with sensitivities 0.24/0.26, specificities 0.98/0.97, PPVs 0.22/0.17, NPVs 0.98/0.98, and <i>c</i>-indices 0.61/0.61 for BWH/AJCC8.</p><h3>Conclusions</h3><p>Both systems performed similarly in predicting poor outcomes in non-HNCSCCs. Specificity and NPV were high, sensitivity and PPV were low, and <i>c</i>-indices were moderately high. As the <i>c</i>-indices were comparable to those seen in the HNCSCC literature, it is reasonable to use the BWH and AJCC8 staging systems for tumors located off the head and neck. However, further refinement of CSCC staging systems is needed to improve prognostication.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"27 1","pages":"181 - 188"},"PeriodicalIF":8.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Safety Data of Dupilumab for the Treatment of Moderate‑to‑Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults","authors":"Richard G. Langley,&nbsp;Guy Gherardi,&nbsp;Anna Coleman,&nbsp;Marius Ardeleanu,&nbsp;Ainara Rodríguez-Marco,&nbsp;Stephane Levy,&nbsp;Ashish Bansal,&nbsp;Zhen Chen,&nbsp;Ana B. Rossi,&nbsp;Brad Shumel,&nbsp;Faisal A. Khokhar","doi":"10.1007/s40257-025-00952-w","DOIUrl":"10.1007/s40257-025-00952-w","url":null,"abstract":"<div><h3>Background</h3><p>Atopic dermatitis (AD) significantly affects quality of life in patients of all ages and requires long-term treatment. Dupilumab is approved for uncontrolled moderate-to-severe AD in patients aged ≥ 6 months and in other type 2 inflammatory diseases. Data from placebo-controlled, randomized clinical trials (RCTs) and long-term open-label extensions (OLEs) enable comprehensive assessment of dupilumab’s safety profile for up to 5 years.</p><h3>Objective</h3><p>To integrate short- and long-term dupilumab safety data in patients with moderate-to-severe AD.</p><h3>Methods</h3><p>We describe safety from eight phase 3 trials with &gt; 7000 patient-years of dupilumab use: five 16-week RCTs in children (6 months–11 years, with concomitant topical corticosteroids [TCS]) and adolescents and adults (≥ 12 years, without TCS); one 52-week RCT in adults (with TCS); and two OLEs in children and adolescents (6–11- and 12–18-year cohorts, ± TCS, duration ≤ 1 year) and adults (± TCS, duration ≤ 5 years).</p><h3>Results</h3><p>The proportion of patients experiencing ≥ 1 treatment-emergent adverse event (TEAE) in RCTs was lower with dupilumab versus placebo in children/infants and was similar with dupilumab versus placebo in adults/adolescents. Exposure-adjusted incidence rates with longer-term treatment in OLEs were similar to the RCTs. Most TEAEs reported in RCT and OLE studies were mild to moderate and not related to study drug (per investigators). Fewer patients in the dupilumab versus placebo treatment arms experienced serious TEAEs (16-week RCTs: infants/children 0.8% vs 3.0%; adults/adolescents 2.0–2.2% vs 4.6%; 52-week RCT: 3.2–3.6% vs 5.1%). Common TEAEs that had higher incidence rates with dupilumab compared with placebo in RCTs included injection-site reactions (Medical Dictionary for Regulatory Activities High Level Term) and conjunctivitis (clustered term). Serious infections and non-herpetic skin infections were more frequent with placebo.</p><h3>Conclusions</h3><p>In the most comprehensive dupilumab safety assessment to date, safety was consistent with the known dupilumab safety profile. [Graphical abstract and video abstract available.]</p><h3>Trial Registration</h3><p>ClinicalTrials.gov Identifiers: NCT03346434; NCT03345914; NCT03054428; NCT02277743; NCT02277769; NCT02260986; NCT01949311; NCT02612454. EudraCT: 2016-000955-28; 2016-004997-16; 2015-004458-16; 2014-001198-15; 2014-002619-40; 2013-003254-24; 2013-001449-15; 2015-001396-40. </p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><h3>Video Abstract</h3>\u0000<div><div><div><iframe></iframe></div></div><div><p>The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children,Adolescents, and Adults(MP4 64,891 KB)</p></div></div></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 6","pages":"981 - 1002"},"PeriodicalIF":8.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00952-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Ulcers Mimicking Pyoderma Gangrenosum: A Prospective Cohort Study","authors":"Sarah L. Becker,&nbsp;Katelyn Downey,&nbsp;Justin Ng,&nbsp;Alex G. Ortega-Loayza","doi":"10.1007/s40257-025-00986-0","DOIUrl":"10.1007/s40257-025-00986-0","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"27 1","pages":"145 - 147"},"PeriodicalIF":8.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Treatments in Moderate-to-Severe Atopic Dermatitis in Pediatric Patients up to 12 Years of Age: Real-World Treatment Outcomes from the PEDISTAD Registry","authors":"Amy S. Paller,&nbsp;Danielle Marcoux,&nbsp;Michele Ramien,&nbsp;Eulalia Baselga,&nbsp;Vania Oliveira Carvalho,&nbsp;Ledit R. F. Ardusso,&nbsp;Marlies de Graaf,&nbsp;Suzanne Pasmans,&nbsp;Mirna Toledo-Bahena,&nbsp;Cory Rubin,&nbsp;Joel C. Joyce,&nbsp;Lara Wine Lee,&nbsp;Rajan Gupta,&nbsp;Bryan Adams,&nbsp;Marius Ardeleanu,&nbsp;Annie Zhang","doi":"10.1007/s40257-025-00962-8","DOIUrl":"10.1007/s40257-025-00962-8","url":null,"abstract":"<div><h3>Background</h3><p>Atopic dermatitis (AD), a chronic systemic disease, can cause intense skin itching and negatively impact sleep, mood, and quality of life (QoL) for patients and families.</p><h3>Methods</h3><p>PEDISTAD is an ongoing, 10-year, observational registry describing disease characteristics, atopic comorbidities, and treatment patterns in pediatric patients (aged &lt;12 years at enrollment) with moderate-to-severe AD. This 3-year interim analysis evaluates clinician-reported and caregiver-reported/patient-reported outcomes (Eczema Area and Severity Index [EASI], percent body surface area affected, worst itching/scratching, Children’s Dermatology Life Quality Index, and Dermatitis Family Impact) in children treated with dupilumab, methotrexate, and/or cyclosporine. Outcomes were assessed as change from therapy start to last observation (either data cutoff date or treatment discontinuation).</p><h3>Results</h3><p>Mean (±SE) EASI scores at the time of the last 3-year interim observation were consistent with mild disease in the dupilumab cohort and moderate disease in the methotrexate and cyclosporine cohorts. Improvements in pruritus were numerically greater in the dupilumab cohort relative to the methotrexate and cyclosporine cohorts, while improvements in QoL were similar in the dupilumab and methotrexate cohorts, with no significant change in the cyclosporine cohort. Rates of AD exacerbation were numerically lower with dupilumab treatment relative to methotrexate treatment which were numerically lower than cyclosporine treatment. Dupilumab discontinuation rates were numerically lower relative to methotrexate which were numerically lower than cyclosporine.</p><h3>Conclusions</h3><p>This PEDISTAD 3-year interim analysis of dupilumab, methotrexate, and cyclosporine treatment in children with AD demonstrates numerically greater improvements in AD signs, symptoms and QoL with dupilumab treatment relative to methotrexate and cyclosporine [Video abstract and graphical abstract available].</p><h3>Clinical Trial Registration</h3><p>NCT03687359.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><h3>Video abstract</h3>\u0000<div><div><div><iframe></iframe></div></div><div><p>Supplementary file1 (MP4 58163 KB)</p></div></div></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 6","pages":"1031 - 1043"},"PeriodicalIF":8.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00962-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program","authors":"Brett King,&nbsp;Jennifer Soung,&nbsp;Christos Tziotzios,&nbsp;Lidia Rudnicka,&nbsp;Pascal Joly,&nbsp;Melinda Gooderham,&nbsp;Rodney Sinclair,&nbsp;Natasha A. Mesinkovska,&nbsp;Carle Paul,&nbsp;Yankun Gong,&nbsp;Susan D. Anway,&nbsp;Helen Tran,&nbsp;Robert Wolk,&nbsp;Samuel H. Zwillich,&nbsp;Alexandre Lejeune","doi":"10.1007/s40257-025-00976-2","DOIUrl":"10.1007/s40257-025-00976-2","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 6","pages":"1065 - 1065"},"PeriodicalIF":8.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00976-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Upadacitinib in Patients With Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results Through 140 Weeks","authors":"Alan D. Irvine,&nbsp;Vimal H. Prajapati,&nbsp;Emma Guttman-Yassky,&nbsp;Eric L. Simpson,&nbsp;Kim A. Papp,&nbsp;Andrew Blauvelt,&nbsp;Chia-Yu Chu,&nbsp;H. Chih-ho Hong,&nbsp;Linda F. Stein Gold,&nbsp;Marjolein de Bruin-Weller,&nbsp;Thomas Bieber,&nbsp;Kenji Kabashima,&nbsp;David Rosmarin,&nbsp;Cristina Sancho,&nbsp;Brian M. Calimlim,&nbsp;Ayman Grada,&nbsp;Yang Yang,&nbsp;Xiaoqiang Wu,&nbsp;Gweneth Levy,&nbsp;Eliza M. Raymundo,&nbsp;Henrique D. Teixeira,&nbsp;Jonathan I. Silverberg","doi":"10.1007/s40257-025-00975-3","DOIUrl":"10.1007/s40257-025-00975-3","url":null,"abstract":"<div><h3>Background</h3><p>Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe atopic dermatitis (AD) in adults and adolescents; long-term efficacy and safety data beyond 1 year are needed.</p><h3>Objective</h3><p>The aim was to evaluate the long-term efficacy and safety of upadacitinib treatment through 140 weeks in patients with moderate-to-severe AD.</p><h3>Methods</h3><p>Measure Up 1 (MeUp1; NCT03569293), Measure Up 2 (MeUp2; NCT03607422), and AD Up (NCT03568318) are ongoing, phase 3, randomized clinical trials evaluating upadacitinib 15 mg (UPA15) and 30 mg (UPA30) in adults and adolescents with moderate-to-severe AD. This interim analysis evaluated efficacy and safety through week 140. At baseline, patients were randomized 1:1:1 to receive once-daily UPA15, UPA30, or placebo alone (MeUp1/2) or with concomitant topical corticosteroids (AD Up). At week 16, patients initially randomized to placebo were rerandomized 1:1 to UPA15 or UPA30. Skin and itch efficacy assessments included achievement of ≥ 75%/≥ 90%/100% improvement from baseline in Eczema Area and Severity Index (EASI 75/90/100), validated Investigator Global Assessment for AD score of clear/almost clear (vIGA-AD 0/1), and ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (∆WP-NRS≥4). Safety assessments included incidence of treatment-emergent adverse events.</p><h3>Results</h3><p>A total of 2782 patients were randomized in MeUp1/2 or AD Up. Efficacy response rates, including optimal outcomes such as EASI 90 and WP-NRS score of 0/1, were sustained through week 140 in all three studies. At week 140, EASI 75 was achieved by 85.5%/90.5% (UPA15/UPA30; integrated MeUp1/2) and 81.5%/90.0% (UPA15/UPA30; AD Up) of patients, and vIGA-AD 0/1 was achieved by 56.6%/64.4% (UPA15/UPA30; integrated MeUp1/2) and 52.0%/56.8% (UPA15/UPA30; AD Up) of patients. Over 60% of patients across all three studies achieved ∆WP-NRS≥4 at week 140. Pooled safety data across all three studies demonstrated safety profiles consistent with 16-week and 52-week analyses.</p><h3>Conclusions</h3><p>UPA15 and UPA30 with and without topical corticosteroids demonstrated robust, durable efficacy and a favorable safety profile through 140 weeks in adults and adolescents with moderate-to-severe AD.</p><h3>Trial Registration</h3><p>Measure Up 1 (NCT03569293; https://clinicaltrials.gov/study/NCT03569293), Measure Up 2 (NCT03607422; https://clinicaltrials.gov/study/NCT03607422), and AD Up (NCT03568318; https://clinicaltrials.gov/study/NCT03568318).</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 6","pages":"1003 - 1016"},"PeriodicalIF":8.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00975-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining “Flares” in Atopic Dermatitis: A Narrative Review","authors":"Joseph F. Merola,&nbsp;Stephan Weidinger,&nbsp;Sally Y. Tan,&nbsp;Kassim Rahawi,&nbsp;Cori Gray","doi":"10.1007/s40257-025-00966-4","DOIUrl":"10.1007/s40257-025-00966-4","url":null,"abstract":"<div><p>Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by fluctuating disease activity. Exacerbations of AD signs and/or symptoms, or flares, have a significant impact on patient quality of life and may require modification or escalation of treatment. However, research into preventing and managing flares may be hampered by the lack of consensus on a clear, clinically relevant, measurable definition of flare. This narrative review provides an overview of disease flare frameworks established through previous systematic literature reviews, flare definitions proposed by American and European guidelines, as well as those used in randomized controlled trials and observational studies published between January 2014 and September 2024. It identifies a range of flare definitions in use in the literature, the majority of which are based on clinician-reported outcomes, with very few referring to the patient perspective. Given the highly individualized experience of disease flare in patients with AD, incorporating the perspective of patients, alongside established measures of disease activity, is vital for creating and validating a definition that is clinically relevant.</p></div>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":"26 6","pages":"905 - 921"},"PeriodicalIF":8.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40257-025-00966-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}