BACKGROUND AND OBJECTIVES:Systemic treatment of pregnant/breastfeeding atopic dermatitis (AD) patients is challenging due to limited safety data. We explored treatment practices with systemic agents, including the guideline-recommended cyclosporine as the first systemic choice as well as emerging therapies, in this vulnerable population. PATIENTS AND METHODS:The Global Allergy and Asthma Excellence Network (GA2LEN) ADCARE initiative collected data from physicians worldwide who treat pregnant women with AD. Physicians completed an electronic questionnaire on the use of systemic agents in pregnant/breastfeeding AD patients. RESULTS:103 physicians from 32 countries completed the survey, primarily dermatologists (n = 48) or allergologists (n = 43). Antihistamines were the systemic drug most often considered to be used during pregnancy/breastfeeding (n = 73/81, 90.1%), with fewer physicians considering the use of systemic agents for the first trimester compared to later stages of pregnancy. For acute flares, systemic corticosteroids (n = 34/80, 42.5%) were preferred, followed by biologics and antihistamines (each n = 15/80, 18.8%). Although the guideline-recommended cyclosporine is sometimes considered for AD during pregnancy (n = 38/81, 46.9%), it was rarely considered as the preferred drug by physicians (n = 1/80, 1.25%). CONCLUSIONS:Our study shows a misalignment between guideline recommendations and prescription patterns and highlights an unmet need for knowing and using the existing recommendations.

BACKGROUND:Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life-threatening disease that has received little attention focusing on its prognostic markers. OBJECTIVE:We evaluated the association between novel inflammatory markers and in-hospital mortality. We also proposed and validated a risk stratification model to aid early intervention. METHODS:This international multicenter, retrospective cohort study included 169 patients diagnosed with DRESS from Taiwan, Singapore, and Japan, collecting demographics and laboratory markers within 3 days of diagnosing DRESS. Inflammatory markers were calculated, and statistical analyses, including logistic regression and receiver operating characteristic curve analysis. Predictive models were developed with internal validation using leave-one-out cross-validation. RESULTS:Lower hemoglobin-to-red blood cell distribution width ratio, higher platelet-to-lymphocyte ratio, and lower monocyte count are identified as significant predictors of mortality in a multivariate analysis. A predictive model for DRESS-related mortality, incorporating the significant inflammatory markers and underlying disease (malignancy, autoimmune disease, and cardiovascular disease), demonstrated good discrimination ability and acceptable accuracy. LIMITATION:The retrospective design, along with factors like interhospital transfers, and underlying malignancies are limitations. CONCLUSION:The presence of these novel inflammatory markers and the development of risk stratification model may be of value to stratification of the severity of DRESS.

Needs edits as it misses the important point of specifying the non-corticosteroids and should not be in the past tense. "Atopic dermatitis (AD) is a skin disease that causes red, dry skin patches that may itch intensely, and may be persistent or intemittent. Most patients with mild-to-moderate AD use topical corticosteroids or topical non-steroids to help them get better. This study looked at how dermatologists treat AD in different parts of the world. Dermatologists in North America, the Middle East, Asia, South America and the UK were asked questions about how they treat AD with topical medications. Most dermatologists use a type of cream or ointment called topical corticosteroids (TCSs) as the first treatment for <= 4 weeks. Weaker TCSs are used for younger patients and sensitive parts of the body. After using TCSs for a few weeks, patients visit their dermatologist to check if the treatment is working. Dermatologists advise patients to continue with the same TCS, use less of the TCS or change to non-steroid topical creams or ointments such as calcineurin inhibitors, crisaborole or topical JAK inhibitors. Sometimes treatments are changed if the patient's skin becomes infected, reacts badly to the medication or there are concerns about side effects. Patients also change treatment if their AD worsens. Sometimes it is difficult for patients to access treatments where they live. This study gives important information about how dermatologists treat mild-to-moderate AD. Treatment depends on factors like the patient's age, how severe the disease is, and if the patient is worried about using some creams and ointments. This information should help dermatologists plan the best treatment for patients with AD.

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. The aim was to evaluate the long-term efficacy and safety of upadacitinib treatment through 140 weeks in patients with moderate-to-severe AD. 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 https://clinicaltrials.gov/study/NCT03569293 ), Measure Up 2 (NCT03607422; https://clinicaltrials.gov/study/NCT03607422 ), and AD Up (NCT03568318; https://clinicaltrials.gov/study/NCT03568318 ).

The burden of atopic dermatitis (AD) is significant, with a substantial impact on quality of life (QoL). This cross-sectional study aimed to ascertain the burden of AD, its impact on QoL, and associated costs. Patients with moderate-to-severe AD were enrolled from eight territories, namely Hong Kong, India, Japan, Mainland China, Singapore, South Korea, Taiwan, and Thailand. After screening was performed and informed consent was obtained, eligible participants were asked to provide responses on their AD symptoms, severity, treatment, and out-of-pocket costs via an online survey. QoL was assessed using EQ-5D-5L and Dermatology Life Quality Index (DLQI), while productivity loss was quantified using the Work Productivity and Activity Impairment (WPAI) questionnaire. Data from completed submissions were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory. Median age of enrolled patients (N = 1103) was 41.0 years (interquartile range, IQR 16.0). The majority of patients reported that their head/neck, trunk, upper limbs, and lower limbs were affected during a flare. Topical (74.2

Introduction:Upadacitinib has demonstrated high andrapid rates of efficacy in adolescent and adult patients withmoderate-to-severe atopic dermatitis (AD) as assessed bythe Eczema Area and Severity Index (EASI). This post hocanalysis assessed the EASI response in four anatomical re-gions for patients with moderate-to-severe AD treated withupadacitinib compared to dupilumab over 24 weeks.Methods:Data from patients randomized 1:1 to receiveupadacitinib 30 mg extended-release tablet orally once dailyor dupilumab 300 mg by subcutaneous injection every2 weeks after a loading dose of 600 mg in the Heads Upstudy were analyzed for achievement of >= 75%,>= 90%, or100% reduction of EASI in four body regions: (1) head andneck, (2) trunk (including genitals), (3) upper limbs, and (4)lower limbs (including buttocks) at each study visit throughweek 24. Patient response data from the Head and NeckPatient Global Impression of Severity (HN-PGIS) were alsoanalyzed at each study visit for comparison of upadacitinibto dupilumab.Results:Greater proportions of patientstreated with upadacitinib versus dupilumab achieved skinclearance rates of >= 75% (EASI 75) at week 1 and higherclearance rates of >= 90% (EASI 90) or 100% (EASI 100) byweek 4 or earlier in all four body regions. This difference was maintained at each visit through week 24 for both EASI 90and EASI 100. Patient responses on the HN-PGIS indicatedthat a greater proportion of patients (nominalpvalue<0.05)treated with upadacitinib compared to dupilumab reportedthat AD symptoms in the head and neck region were absentor minimal as early as week 1.Conclusion:Compared todupilumab, upadacitinib treatment provided higher rates ofrapid, sustained efficacy for the head and neck, trunk, upperlimbs, and lower limbs for the treatment of moderate-to-severe AD as measured by the EASI and supported by pa-tient responses.(c) 2024 The Author(s).Published by S. Karger AG, Basel

Abstract Introduction The GLOBOSTAD study aims to assess the extended real-world effectiveness of dupilumab in patients with atopic dermatitis (AD) receiving dupilumab as part of their normal care. Objectives To report patient-reported outcomes and physician-­assessed AD clinical measures for evaluating disease characteristics, severity, and treatment effectiveness 1 year after initiating dupilumab treatment. Methods This 5-year, multinational, prospective, observational study (NCT03992417) enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. Assessments were performed at baseline, 3 months (± 1 month), 6 months (± 2 months), and 12 months (± 2 months). Data are reported as observed for enrollment/safety (N = 955; data cutoff: March 2023) and follow-up (N = 903) populations including 13 adolescent patients with AD (≥12 and <18 years old). Results In this study, 758/863/705 patients completed ≥1 follow-up assessment at 3 months/6 months/12 months, respectively. During the study the mean (standard deviation [SD]) Eczema Area and Severity Index (EASI; >21 = severe; ≤7 = mild/no disease) scores decreased from 25.1 (12.8) at baseline to 6.1 (8.0) at 3 months, 4.6 (6.4) at 6 months and sustaining throughout the observation period [12 months; 4.2 (8.4)]. Mean Patient-Oriented Eczema Measure (SD) improved from 19.7 (6.4) at baseline descending to 8.7 (6.6) at 3 months, 7.7 (6.0) at 6 months and 7.1 (5.8) at 12 months. A significant improvement was also observed in Dermatology Life Quality Index (DLQI) from 13.7 (7.1) to 5.3 (5.1) to 4.4 (4.4) to 3.9 (4.2); and children’s DLQI from 12.2 (6.2) to 2.7 (2.9) to 2.9 (3.0) to 4.8 (4.8) by the end of the 3, 6 and 12-months observational period respectively. Dupilumab-related adverse events were reported in 187 (20.8%) patients. Conclusions In a real-world scenario, the initiation of dupilumab treatment led to early and sustained improvements in AD outcome measures throughout the 1-year observational period. Safety data remained consistent with findings from previous studies.

Acral melanoma is an aggressive type of melanoma with unknown origins, arising on the sole, palm, or nail apparatus. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. Our study examined exome sequencing data from 139 tissue samples, spanning different progression stages, collected from 37 patients. We found that 78.4% of the melanomas displayed one or more clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22. These genomic “hailstorms” were typically shared across all progression stages within individual patients. Genetic alterations known to activate TERT also arose early. By contrast, mutations in the MAP- kinase pathway appeared later during progression, often leading to different tumor areas harboring non-overlapping driver mutations. We conclude that the evolutionary trajectories of acral melanomas substantially diverge from those of melanomas on sun-exposed skin, where MAP-kinase pathway activation initiates the neoplastic cascade followed by immortalization later. The punctuated formation of hailstorms, paired with early TERT activation, suggests a unique mutational mechanism underlying the origins of acral melanoma. Our findings highlight an essential role for telomerase, likely in re-stabilizing tumor genomes after hailstorms have initiated the tumors. The marked genetic heterogeneity, in particular of MAP-kinase pathway drivers, may partly explain the limited success of targeted and other therapies in treating this melanoma subtype.

Introduction Dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD) in randomized controlled trials. Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Objective To report dupilumab effectiveness, through physician-assessed AD clinical tools that measure disease severity over time, and a summary of adverse events in patients one year after initiating treatment. Methods The GLOBOSTAD five-year, multinational, prospective, observational study (NCT03992417) enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N = 955; data cutoff: March 2023) and follow-up (N = 903) populations. Results 758/863/705 patients completed ≥1 follow-up assessment at 3M/6M/12M, respectively. During the study, mean (SD) eczema area and severity index (EASI; >21 = severe; ≤7 = mild/no disease) score rapidly improved from 25.1 (12.8) at baseline to 6.1 (8.0) at 3M, and was sustained until the end of observation period [12M; 4.2 (8.4)]. Similarly, scoring of atopic dermatitis (SCORAD; >50 = severe; <25 = mild/no disease) score improved from 59.3 (16.6) at baseline to 25.3 (16.4) at 3M, further improving to [17.6 (13.0)] at 12M. Adverse events considered related to dupilumab by the investigator were reported in 187 (19.6%) patients. Adverse events leading to permanent dupilumab discontinuation were reported in 23 (2.4%) patients. Conclusion In a real-world scenario, clinical AD assessments rapidly improved upon initiating dupilumab treatment, and were sustained through the end of the one-year observation period. Safety data were consistent with previous studies.

Limited evidence is available on real-world management of atopic dermatitis (AD) among Asian adults. This cross-sectional study aimed to assess current approaches in AD diagnosis and management in Asia. Practising dermatologists regularly treating patients with moderate-to-severe AD were recruited from eight Asia–Pacific territories, namely Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. A survey was administered to eligible dermatologists after screening and taking informed consent. Data from fully completed submissions were analysed using descriptive statistics. The study was reviewed by the institutional review board in each territory. Data from 271 dermatologists were included for analysis. About one-third (31.7

Rapid progress made in the management of atopic dermatitis (AD) in recent years and the differences in patient journey between Asian and non-Asian populations call for a review of current atopic dermatitis landscape in Asia. A roundtable meeting with nine regional dermatological experts was held in June 2023 to discuss the optimal management approaches for moderate-to-severe AD, focusing on the use of advanced therapies. Disease burden on patients’ quality of life, treatment adherence, and financial constraints were identified as major concerns when managing patients with moderate-to-severe AD in parts of Asia. It was agreed that the Hanifin and Rajka’s criteria or the UK Working Party’s Diagnostic Criteria for Atopic Dermatitis can be used to guide the clinical diagnosis of AD. Meanwhile, patient-reported outcome scales including the Dermatology Life Quality Index and Atopic Dermatitis Control Tool can be used alongside depression monitoring scales to monitor treatment outcomes in patients with AD, allowing a better understanding for individualized treatment. When managing moderate-to-severe AD, phototherapy should be attempted after failure with topical treatments, followed by conventional disease-modifying antirheumatic drugs and, subsequently, biologics or Janus kinase inhibitors. Systemic corticosteroids can be used as short-term therapy for acute flares. Although these advanced treatments are known to be effective, physicians have to take into consideration safety concerns and limitations when prescribing these treatments. Treatments in AD have evolved and its management varies country by country. Unique challenges across Asian countries necessitate a different management approach in Asian patients with AD.

Abstract IntroductionIntegrated safety data for lebrikizumab (LEB) treatment in moderate-to-severe atopic dermatitis (AD) has been previously published. Conjunctivitis and keratitis were identified as adverse events (AEs) of special interest in the AD ­program. Objectives Further characterize patient-reported conjunctivitis and keratitis AEs in LEB clinical trials for AD. Methods Data from adult and adolescent patients were analyzed in 2 groups: a) LEB 250mg every 2 weeks (LEBQ2W, N=783) vs placebo (PBO, N=404), weeks 0-16 (PC 0-16wk) from 4 clinical trials (ADvocate1, ADvocate2, ADhere, Phase 2b study); and b) patients who received at least one dose of LEB (ALL-LEB, N=1720) from 8 clinical trials (ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE, Phase 2b study). Conjunctivitis and keratitis refer to cluster definitions defined by MedDRA preferred terms conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, giant papillary conjunctivitis; and keratitis, atopic keratoconjunctivitis, allergic keratitis, ulcerative keratitis, vernal keratoconjunctivitis, respectively. Exposure adjusted incidence rates (IR) are provided as per 100 patient-years. Results In PC 0-16wk, at baseline, similar proportions of LEB (21.5%) and PBO (19.3%) patients had medical history (MH) of conjunctivitis. Of ALL-LEB, 22.2% had MH of conjunctivitis; of those with conjunctivitis or keratitis AE, 40% had MH of conjunctivitis. In PC 0-16wk, conjunctivitis cluster was reported by 8.5% (IR:30.6) LEBQ2W vs 2.5% (IR:8.9) PBO; keratitis cluster was reported by 0.6% (IR:2.2) and 0.3% (IR:0.9) of patients, respectively. All conjunctivitis and keratitis events in PC 0-16wk were mild or moderate in severity; 5 events (3 conjunctivitis, 2 keratitis) led to treatment discontinuation (LEBQ2W) vs 1 conjunctivitis event (PBO). ALL-LEB treatment duration ranged from 1 dose to 100 weeks. In ALL-LEB, conjunctivitis cluster was reported by 10.6% (IR:12.2), with the majority being mild or moderate (10.3%) and 0.3% severe. Keratitis was reported by 0.5% (IR:0.6), with 1 severe event of vernal keratoconjunctivitis. Conjunctivitis and keratitis events resulted in 17 (1.0%) and 3 (0.2%) treatment discontinuations, respectively. Similar proportions of adult (11.3%; 0.6%) and adolescent (8.3%; 0.3%) patients reported conjunctivitis and keratitis events. The majority were reported within first 16 weeks of treatment. ConclusionsConjunctivitis is an AE reported by LEB-treated patients. Patients with MH of conjunctivitis may have higher risk of developing treatment-emergent conjunctivitis or keratitis. Most events were mild or moderate in severity, did not lead to treatment discontinuation, were reported within first 16 weeks of treatment, and IR did not increase with longer duration of exposure.

Abstract Introduction In multiple randomized controlled clinical trials, dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD). Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Comprehensive data on Asian patients with moderate-to-severe AD treated with dupilumab are limited. Objectives To report patient-reported outcomes and physician-assessed AD clinical measures to evaluate disease characteristics, severity, and treatment effectiveness 1 year after initiating dupilumab treatment in Asian patients. The baseline disease severity and patient demographics have been reported previously1. Methods This 5-year, multinational, multicentre, prospective, observational study (GLOBOSTAD; NCT03992417) included Asian patients ≥12 years-old with moderate-to-severe AD who initiated dupilumab treatment based on country-specific prescribing criteria. Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatology Life Quality Index (DLQI) were assessed at baseline, 3 months (± 1 month), 6 months (± 2 months), and 12 months (± 2 months). Data are reported as observed in patients self-reported as Asian for enrolment/safety (N = 204; data cutoff: March 2023) and follow-up (N = 194) populations. Results During the study, EASI (>21 = severe; ≤7 = mild/no disease) score improved from 28.0 (12.1), mean (SD) at baseline to 7.4 (8.5) at 3 months, 5.7 (6.9) at 6 months, and was sustained until the end of observation period, 12 months, at 4.7 (7.1). Similarly, SCORAD (>50 = severe; <25 = mild/no disease) score improved from 61.5 (16.9) at baseline to 25.4 (16.6) at 3 months, 22.5(14.8) at 6 months, and further improved to 18.6 (13.3) at 12 months. During the study, patients also reported early improvements in POEM, mean (SD) from 19.1 (7.3) at baseline to 8.0 (5.8) at 3 months, 7.6 (5.5) at 6 months, and to 7.2 (5.0) at end of observation period (12 months); PP-NRS decreased from 5.7 (2.3) to 2.1 (2.2) to 1.7 (1.8), and to 1.4 (1.7) at 3 months, 6 months, and 12 months respectively; and DLQI improved from 13.2 (7.4) to 4.9 (4.6) to 4.0 (3.8), and to 4.1 (4.0) at 3 months, 6 months and 12 months respectively. Dupilumab-related adverse events were reported in 44 (21.5%) patients while 4 (2.0%) reported dupilumab-related severe adverse events. Conclusion In Asian patients, the initiation of dupilumab treatment led to early improvements in all AD outcome measures, sustained throughout the 1-year observational period. Safety and treatment effectiveness were consistent with overall population.

Real-world studies complement randomized controlled trials (RCTs) by providing data from a more heterogeneous population treated in a normal practice environment. In several RCTs, dupilumab has demonstrated robust efficacy with acceptable safety in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD study (NCT03992417) are characterizing the patient population treated with dupilumab, their AD treatment patterns, long-term effectiveness, and safety of dupilumab in the real world. The GLOBOSTAD 5-year, multinational, prospective, observational study enrolled patients aged ≥ 12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information, and assessments were performed at baseline, 3 months (± 1 month), 6 months (± 2 months) and 12 months (± 2 months). The data are reported as observed for the enrolment/safety (n = 955; data cutoff March 2023) and follow-up (n = 903) populations. In total, 758, 863 and 705 patients completed at least one follow-up assessment at 3, 6 and 12 months, respectively, with a mean (SD) treatment period of 11.7 (1.2) months. The mean (SD) Eczema Area and Severity Index (EASI; > 21 = severe; ≤ 7 = mild/no disease) at baseline was 25.1 (12.8). During the study, ≥ 75% (EASI 75) and ≥ 90% (EASI 90) reductions in mean EASI scores from baseline were observed in 66.2% and 35.6% of patients at 3 months, 74.6% and 42.4% at 6 months, and 81.0% and 55.8% at the end of the observation period (12 months), respectively. The patient-reported mean (SD) weekly average pruritus numerical rating scale (NRS, range 0–10) at baseline was 6.3 (2.2). A three-point and four-point improvement from baseline or a score of 0 in pruritus NRS was observed in 66.9% and 57.1% of patients at 3 months, 73.6% and 64.1% at 6 months, and 79.0% and 70.3% at 12 months, respectively. Of the follow-up population, 67.4% achieved an absolute pruritus NRS score of ≤ 3 at 3 months, 76.4% at 6 months, and 80.3% at 12 months. Adverse events considered related to dupilumab that led to permanent discontinuation occurred in 2.4% of patients. Patients enrolled in the GLOBOSTAD study achieved rapid improvements in AD signs and symptoms on initiating dupilumab treatment, which were sustained until the end of the 1-year observation period. Safety was consistent with the known dupilumab safety profile. This research was sponsored by Sanofi and Regeneron Pharmaceuticals Inc.