Moderate Atopic Dermatitis Research Articles

390 Efficacy and safety of roflumilast cream 0.15% in adults and children aged ≥6 years with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2)

Abstract Roflumilast is a selective, highly potent phosphodie­sterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). INTEGUMENT-1 (n = 654; NCT04773587) and INTEGUMENT-2 (n = 683; NCT04773600) were identical phase 3 randomized controlled trials conducted in patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of mild or moderate. Patients were randomized 2 : 1 to apply once-daily roflumilast cream 0.15% or vehicle for 4 weeks. The primary efficacy endpoint was vIGA-AD Success [defined as score of 0 (clear) or 1 (almost clear) with 2-grade improvement from baseline] at Week 4. Secondary endpoints included 75% improvement in EASI (EASI-75). At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (INTEGUMENT-1: 32.2% vs. 15.2%; P < 0.0001; INTEGUMENT-2: 28.9% vs. 12.0%; P < 0.0001) and EASI-75 (INTEGUMENT-1: 43.2% vs. 22.0%; P < 0.0001; INTEGUMENT-2: 42.0% vs. 19.7%; P < 0.0001). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with most assessed as mild to moderate in severity. No AE occurred in more than 3.5% of patients in either arm with low rates of application site pain in both the roflumilast- and vehicle-treated patients (INTEGUMENT-1: 2.1% vs. 0.5%; INTEGUMENT-2: 0.9% vs. 0.9%). Local tolerability was favorable with >90% of roflumilast-treated patients reporting no or mild sensation across arms in both trials at any timepoint. Once-daily roflumilast cream 0.15% improved AD across multiple efficacy endpoints while demonstrating favorable safety and tolerability in two phase 3 trials.

377 Real-world use of OPZELURA™: safety analysis at 1 year

Abstract OPZELURA™ (ruxolitinib cream) became the first approved topical Janus kinase inhibitor (JAKi) in the USA on September 21, 2021, for treatment of mild to moderate atopic dermatitis and on July 18, 2022 for nonsegmental vitiligo. This study aims to review postmarketing safety encompassing nearly 14,000 patient-years of treatment during the first year of market approval through September 20, 2022. The Incyte global safety database and the US Food and Drug Administration (FDA) Adverse Event Reporting System were queried for adverse event (AE) reports received for OPZELURA between September 21, 2021 and September 20, 2022. Search of these databases found 294 postmarketing individual case safety reports (ICSRs) containing 585 nonserious AEs, four serious AEs and no fatal AEs. Of the 294 ICSRs, 220 (75%) were received from spontaneous sources and 74 (25%) were received from noninterventional/solicited sources. Consumers reported 221 ICSRs (75%) and 73 (25%) were medically confirmed by a healthcare professional (i.e. nurse, pharmacist and physician). Gender was reported in 257 ICSRs; of these, 81 (32%) involved male patients and 176 (68%) involved female patients. Age was reported in 64 ICSRs (22%), with a median age of 39 years. The AEs (any unfavorable sign, symptom or disease) with frequency >2% out of all events included application site pain (16 events), dermatitis atopic, skin irritation (15 events each), scratch (14 events) and condition aggravated (13 events). Application site pain, skin irritation and scratch were mostly related to an initial issue with cream texture that was rapidly addressed. ‘Dermatitis atopic’ and ‘condition aggravated’ reflected worsening of the underlying condition or lack of improvement. The four serious AEs were skin cancer (two events), pericarditis and thrombocytopenia (one event each), all of which had insufficient information for assessment of relatedness to OPZELURA. Because indications for OPZELURA are inflammatory conditions, OPZELURA has been subject to the same class warnings as oral JAKi that include the risk of serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis, imposed by FDA subsequent to the ORAL Surveillance trial of tofacitinib in rheumatoid arthritis (Kragstrup et al., RMD Open, 2022; 8:e002236). Topical application of OPZELURA results in low systemic bioavailability of ruxolitinib, and serious AEs associated with oral JAKi were not reported with OPZELURA. Safety data from the first year of marketing confirm that OPZELURA is well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.

439 Patients with mild to moderate atopic dermatitis: a first-in-human, open-label, dose-escalating, nonrandomized clinical trial with AMTX-100

Abstract Atopic dermatitis (AD) is a chronic skin disease that affects approximately 10% of the global population and is characterized by epidermal disruption, microbial invasion, intense pruritus and cytokine mediated inflammation. The pathogenesis of AD is primarily associated with Type 2 immune responses, including the elevated expression of Th2 cytokines such as IL-4, IL-5, IL-13 and IL-31; however, studies have demonstrated roles for epithelial cell-derived cytokines (IL-25, IL-33 and thymic stromal lymphopoietin) and Type 3 immune responses (IL-17, IL-22 and IL-23). Given that AD is a heterogeneous disease with potential for the activation of multiple cytokines at once, there is a growing interest in multi-factorial approaches to therapeutic intervention. Evidence indicates that transcription of many genes overexpressed in AD is controlled predominantly by stress responsive transcription factors (SRTFs) like nuclear factor-kB (NF-kB), the master regulator of inflammation. Nuclear factor-kB is translocated from cytoplasm to the nucleus by a complex of two nuclear transport shuttles, importin α5 (IMPα5) and importin β1 (IMPβ1) after docking of the nuclear localization sequences (NLS) of NF-kB with its binding domain on IMPα5. Once in the nucleus, NF-kB activates genes containing its DNA consensus sequence producing mRNA, which are translated into proteins. AMTX-100 is a novel, chimeric, 100% human, 28-amino acid peptide that contains cell-penetrating sequences at its amino terminal end derived from the fibroblast growth factor 4 signal sequence and a small stretch of the NF-kB amino acid sequences containing an NLS involved in nuclear transport of large transcription factors (SRTFs) that contain a similar NLS. This study aims to identify the maximum tolerated dose, safety, tolerability and efficacy of topically applied AMTX-100 CF 1.1% in adult patients with mild to moderate AD. AMTX-100 CF 1.1% was administered topically twice daily for 7 days at five dose levels. Each patient’s first dose was administered at the study clinic by trained site staff. Remaining doses were self-administered by patients at home. The applied amount of AMTX-100 CF 1.1% depended on the percentage of the body surface area (BSA) affected with AD. The primary and safety endpoints were evaluating maximum dose toxicity and treatment-emergent adverse events. Exploratory endpoints were percent change from baseline of the treated BSA and validated Investigator Global Assessments (vIGA) at Days 7 and 21. This open-label, dose-escalation clinical trial was conducted between March 3, 2020 and October 7, 2021, at four clinical centers in the USA. The study included an up to 21-day screening, 7-day treatment and 14-day follow-up period. Thirty-five patients were assessed for eligibility: nine were excluded and 26 were enrolled. Eligible patients were at least 18 years old with mild to moderate AD diagnosed for at least 6 months prior to enrollment. Patients were referred from sites’ databases and outpatient centers. No dose limiting toxicities, treatment-related AEs, serious AEs or significant changes in laboratory measurements occurred in any cohorts. The mean BSA affected by AD decreased from baseline at the end of treatment visit and follow-up visit by 37.5% (P = 0.001) and 37.9% (P = 0.027), respectively. Across study cohorts, vIGA-AD scores improved after intervention. The findings for this Phase I portion of an Adaptive Phase I/II protocol provides support for safety, tolerability and efficacy of AMTX-100 CF 1.1% in adult patients with mild to moderate AD. AMTX-100 CF 1.1% has advanced into Phase II study including safety, efficacy, gene expression (skin and blood) and proteomics (blood) measurements throughout the study.

Topical Chinese herbal medicine in treating atopic dermatitis (eczema): A systematic review and meta-analysis with core herbs exploration

Ethnopharmacological relevanceTopical Chinese herbal medicine (CHM) is commonly used to relieve atopic dermatitis (AD); however, the up-to-date evidence concerning the effectiveness of topical CHM on treating AD is lacking. Moreover, the CHM prescriptions are often too complicated to realize the overall mechanisms of CHM, especially when compared to western medicines (WM). Aim of the studyTo evaluate the effectiveness of topical CHM for treating AD by conducting a meta-analysis on randomized clinical trials (RCTs). MethodsTwenty RCTs comparing topical CHM to active control/placebo were included in the final analysis. The primary outcome was the symptom scores changed from baseline and the effectiveness rate was the secondary outcome. Subgroup analysis on different initial symptom severity and the different interventions in control groups was performed. System pharmacology analysis was performed to explore core CHM and possible pharmacological mechanisms of CHM for AD. ResultsCompared with active/blank placebo, topical CHM seemed more effective (SMD: −0.35, 95 %CI: −0.59 to −0.10, p-value = 0.005, I2 = 60%). The effectiveness rate was higher (RR: 1.29, 95 %CI 1.15–1.44, p-value <0.00001, I2 = 71%). In subgroup analysis, mild and moderate AD patients with topical CHM were more effective than placebo (SMD: −0.28, 95 %CI -0.56 to −0.01, p-value = 0.04, I2 = 5%; −0.34, 95%CI -0.64 to −0.03, p-value = 0.03, I2 = 0%, separately). Topical CHM has 1.25 times more effective than the topical glucocorticoid (95 %CI 1.09–1.43, p-value = 0.001, I2 = 64%). Core CHMs, such as Phellodendron chinense C.K. Schneid., Sophora flavescens Ait., Cnidium monnieri (L.) Cusson, and Dictamnus dasycarpus Turcz., had effects on the pathways on immune and metabolism systems different from WM. ConclusionOur results exploit the potential role of CHM on treating AD, especially for mild and moderate AD.

Evaluation of a paraffin-based moisturizer compared to a ceramide-based moisturizer in children with atopic dermatitis: A double-blind, randomized controlled trial.

Moisturizers are first-line therapy for treatment of atopic dermatitis (AD). Although there are multiple types of moisturizers available, head-to-head trials between different moisturizers are limited. To evaluate if a paraffin-based moisturizer is as effective as ceramide-based moisturizer in children with AD. In this double-blind, randomized comparative trial of pediatric patients with mild to moderate AD, subjects applied either a paraffin-based or ceramide-based moisturizer twice daily. Clinical disease activity using SCOring Atopic Dermatitis (SCORAD), quality of life using Children/Infants Dermatology Life Quality Index (CDLQI/IDLQI), and transepidermal water loss (TEWL) were measured at baseline and at follow-up at 1, 3, and 6 months. Fifty-three patients were recruited (27 ceramide group and 26 paraffin group) with a mean age of 8.2 years and mean disease duration of 60 months. The mean change in SCORAD at 3 months in the ceramide-based and paraffin-based moisturizer groups was 22.1 and 21.4, respectively (p = .37). The change in CDLQI/IDLQI, TEWL over forearm and back, amount and days of topical corticosteroid required, median time to remission and disease-free days at 3 months were similar in both groups. As the 95% confidence interval (CI) of mean change in SCORAD at 3 months in both groups (0.78, 95% CI: -7.21 to 7.52) was not within the predefined margin of equivalence (-4 to +4), the conclusion of equivalence could not be proven. Both the paraffin-based and ceramide-based moisturizers were comparable in improving the disease activity in children with mild to moderate AD.

CO136 Efficacy and Safety of Roflumilast Cream 0.15% in Adults and Children Aged 6 and Older with Mild to Moderate Atopic Dermatitis in Two Phase 3 Integument Trials

CO136 Efficacy and Safety of Roflumilast Cream 0.15% in Adults and Children Aged 6 and Older with Mild to Moderate Atopic Dermatitis in Two Phase 3 Integument Trials

Childhood atopic dermatitis is associated with cardiovascular risk factors in young adulthood-A population-based cohort study.

Studies have indicated that atopic dermatitis (AD) is associated with an increased risk of cardiovascular disease (CVD). However, data are conflicting. Furthermore, the longitudinal effect of childhood AD on cardiovascular risk factors in young adulthood is less investigated. To assess associations between AD in childhood and CVD risk factors in young adulthood. The study encompasses longitudinal data from a population-based birth cohort. Participants with data up to age 24 years were included (n = 2270). The primary outcomes were body mass index (BMI), waist circumference (WC), body fat per cent (BF%) and blood pressure (BP) at 24 years. The secondary outcome was blood lipids. Severe AD was defined as AD in combination with sleep disturbance due to itching. In total, 18.6% (n = 420) had AD at 24 years. Males with AD had higher BMI (βAdj. 0.81, 95% CI 0.15-1.47), BF% (βAdj. 1.19, 95% CI 0.09-2.29), systolic BP (βAdj. 1.92, 95% CI 0.02-3.82), total cholesterol (βAdj. 0.14, 95% CI 0.00-0.28) and LDL cholesterol (βAdj. 0.15, 95% CI 0.02-0.27) compared with males without AD. No associations were seen in females. Current AD with prepubertal onset was associated with increased BMI in both males (βAdj. 0.89, 95% CI 0.11-1.67) and females (βAdj. 0.72, 95% CI 0.11-1.33). At 24 years, 23.1% (n = 97) of all with AD, had severe disease, which was significantly associated with overweight in both sexes, with BMI (βAdj. 1.83, 95% CI 0.72-2.94), WC (βAdj. 4.03, 95% CI 1.54-6.52) and BF% (βAdj. 2.49, 95% CI 0.60-4.39) in females and with BF% (βAdj. 2.96, 95% CI 0.23-5.69) in males, compared with peers with mild to moderate AD. AD in males appears to be associated with CVD risk factors in young adulthood. The duration and severity of AD seem to be of importance in both sexes.

Ocular manifestations of children with atopic dermatitis in Saudi Arabia.

To examine the incidence of ocular abnormalities in children with atopic dermatitis (AD) in Saudi Arabia and its association with the severity of AD. This is a cross-sectional study on 50 children with AD who were between 5 and 16 years of age. The severity of AD was evaluated using the SCORing Atopic Dermatitis (SCORAD) index. All the children underwent slit lamp exams, visual acuity assessment, intraocular pressure measurement, and corneal topography. The children were considered to have an ophthalmic abnormality if one or more of the following signs were present: glaucoma, keratoconus suspicion, in addition to lid, conjunctival, corneal, lenticular, or retinal abnormalities. Based on the SCORAD severity index, 14% of children had mild AD (7/50), 38% had moderate AD (19/50), and nearly half had severe AD. More than half the children exhibited facial involvement, and half had peri-orbital signs. The mean SCORAD index was 35.75. The mean age was 10.48±3.6y, and the cohort showed a slight male predominance (54% males). Both eyes of the 50 children in the cohort were studied. Based on the ocular examinations, 92% of the patients showed ocular abnormalities: lid abnormalities (27/50) followed by keratitis (22/50). Four patients had moderate risk for keratoconus in one eye and eight patients were suspected to have keratoconus. However, SCORAD severity index was not associated with age, sex, or the number or presence of ophthalmic abnormalities. This is the first study in Saudi Arabia to evaluate the prevalence of ocular manifestations in children with AD. The results indicate that the majority of children with AD have ocular abnormalities that mainly include lid abnormalities. Based on these findings, larger scale studies are needed to affirm whether regular screening for ophthalmic abnormalities would be beneficial for children with AD in terms of early intervention and prevention of sight-threatening complications.

Reduction in hospitalisations with dupilumab in Japanese adults with atopic dermatitis in a real‐world setting

AbstractBackgroundIn a recent post hoc analysis of multinational clinical trial data, dupilumab treatment for patients with moderate or severe atopic dermatitis (AD) reduced all‐cause and AD‐related hospitalisations.ObjectivesWe studied the impact of dupilumab on health care resource utilisation (HCRU) and AD medication by comparing use during the 6 months either side of starting dupilumab (index) in a real‐world setting.MethodsThis observational, retrospective, cohort study used Japanese hospital claims data (1 April 2018 to 28 February 2019). A total of 357 patients (mean [range] age 45 [15–92] years; 65.5% male) with ≥1 AD diagnosis and ≥1 dupilumab prescription were included. Outcome variables included AD treatments and HCRU during the 6 months pre‐ and post‐index.ResultsThe number of all‐cause hospitalisations decreased by 43.1% (from 51 in the 6 months before to 29 in the 6 months after dupilumab initiation), with a 96.0% reduction in skin/subcutaneous tissue disease‐related hospitalisations (25 to 1). Use of nonsteroidal systemic immunosuppressants, phototherapy and systemic corticosteroids decreased (by 59.8%, 59.5% and 30.6%, respectively) after dupilumab initiation. At 180 days after dupilumab initiation, 86.8% of patients were still taking dupilumab.ConclusionsOverall, these results suggest that dupilumab can reduce skin/soft tissue‐related hospitalisations and use of various other AD medications in a real‐world setting.

Definition of the Clinical Characteristics of Patients with Moderate and Severe Atopic Dermatitis for Whom Narrow-Band UVB (NB-UVB) and Medium-Dose UVA1 Phototherapies Are Still Valuable Treatment Options at the Age of Biologics.

Narrow-band (NB) UVB and UVA1 have been successfully used for the treatment of atopic dermatitis (AD) since the 1980s, but the clinical indications for their use "at the age of biologics" remain to be assessed. From 2013 to 2017, 145 patients underwent a first treatment cycle with phototherapy. They achieved a median final EASI score of 9.90 with UVA1 and 13.70 with NB-UVB. The rates of patients achieving an IGA score of 0/1 persistent for at least 6 months were 33% with UVA1 and 28% with NB-UVB, and the rates with an EASI90 improvement were 10.9% with UVA1 and 11.0% with NB-UVB. The cut-off baseline EASI values for a good probability to achieve a 0/1 IGA were 24.4 with UVA1 and 24.7 with NB-UVB. A 0/1 IGA persistent for at least 6 months was more likely to be achieved by patients with a history of flares interspersed with periods of mild or no disease. From 2018, we only enrolled patients with the above-mentioned characteristics. The number of treated patients was lower, but the final EASI score, the rate of patients achieving IGA 0/1 persistent for at least 6 months, and EASI90 were significantly higher. Medium-dose UVA1 and NB-UVB phototherapies remain useful for the treatment of AD patients with a baseline EASI score lower than 24.4 and 24.7, respectively, and a medical history of flares followed by prolonged periods of complete or near-complete remission.

Open-label, single-arm, single-center clinical study on the effectiveness and safety of a moisturizer containing tocotrienol-rich composition in children with mild to moderate atopic dermatitis.

Little is known about antioxidant efficacy of topical vitamin E on atopic dermatitis (AD) due to lack of controlled clinical studies. The study evaluates the effectiveness and safety of a topical moisturizer containing tocotrienol-rich composition over 12 weeks on patients aged between 1 month and 12 years with mild to moderate AD. We conducted a 12 weeks, prospective, open-label clinical study on the effect of tocotrienol as an adjunct to conventional treatment. This study was approved by the Ethics Committee for Research Involving Human Subject. JKEUPM-2019-274 (NMMR-19-1588-49234). Thirty AD patients with a mean age of 2.77 ± 3.05 were enrolled in the study. At week-12, significant reduction of investigator global assessment (63.4%), Patient-Oriented Scoring Atopic Dermatitis Index (PO-SCORAD) (65%), and SCORAD (52.3%) was noted (p < 0.05). There was also a significant decreased in pruritus intensity (46%, p < 0.05). Similarly at week-12, Infant's Dermatitis Quality of Life Index and Children's Dermatology Life Quality Index were found to improve significantly compared to baseline (p < 0.05). Instrumental assessment revealed improvement in TEWL and erythema index, 49.7% and 17.4%, respectively. No adverse reaction was observed. 95% of patients were satisfied with the moisturizer and 90% perceived it to be better than the one in the market. There was a 55.07% reduction in the use of hydrocortisone 1% cream toward the end of the study (p < 0.05). The results suggested that tocotrienol-rich moisturizer is safe and effective in the management of AD in young children.

Therapeutic effects and mechanisms of Ku-Gan formula on atopic dermatitis: A pilot clinical study and modular pharmacology analysis with animal validation.

Atopic dermatitis (AD) is a persistent, recurrent inflammatory skin disorder with a rapid upward trend worldwide. The first-line treatment for AD consists of topical medicines such as topical corticosteroids (TCSs). However, long-term use of conventional topical medicine results in side effects and recurrence, presenting therapeutic challenges for the management of AD. Ku-Gan formula (KG) has been extensively used to treat skin diseases since the Song dynasty. In particular, topical administration of the KG alleviates the cutaneous symptoms of AD and reduces recurrence rates with a good safety profile; however, the mechanisms of the KG's action remain unknown. The current study aimed to evaluate the efficacy and safety of KG in AD patients and to investigate the molecular mechanisms that underlie the efficacy of KG in the treatment of AD. A single-arm prospective pilot study with historical controls was conducted. This study evaluated 11 patients with mild to moderate AD, who underwent topical KG treatment. The primary outcome was the change in local eczema area and severity index (EASI) scores. The secondary outcomes included the recurrence rate and safety. The recurrence rate were compared to those of a matched historical control group. Secondly, modular pharmacology analysis was used to elucidate the therapeutic mechanism of KG in AD treatment by identifying the hub genes and kernel pathways. Moreover, we evaluated treatment effects and verified modular pharmacology-based findings using the calcipotriol (MC903)-induced mouse model and bioinformatics analysis. Our clinical pilot study demonstrated that the KG wet wrapping could effectively ameliorate skin lesions in AD patients with a significant drop from 4.18 to 1.63 in local EASI. Compared to the historical controls, KG had a reduced recurrence rate (36%) and a longer median time to relapse (>12 weeks). Modular pharmacology analysis identified the hub genes including IL6, IL1B, VEGFA, STAT3, JUN, TIMP1 and ARG1, and kernel pathway including IL-17 signaling pathway of KG. Pharmacodynamic results suggested that KG ameliorated skin symptoms and demonstrated no less efficacy than halcinonide (HC) in MC903-induced AD-like mice. In addition, KG regulated the mRNA expression of hub genes as well as the related genes involved in IL-17 signaling pathway including Il25, Il17a,Traf3ip2, and Traf6, in skin lesions of AD-like mice. These results showed that KG is a safe and effective topical treatment for AD with low recurrence. In addition, our study identified potential molecular pathways and therapeutic candidate targets of the KG formula, providing evidence for its clinical applicability in AD.

Impact of daily use of emollient ‘plus’ on corticosteroid consumption in patients with atopic dermatitis: An open, randomized controlled study

Emollients are the baseline treatment for mild or moderate atopic dermatitis (AD) to improve the epidermal barrier and provide anti-irritant and anti-pruritic effects. Emollient 'plus' can influence the skin microbiome of atopic eczema patients. To evaluate the benefits of using Emollient 'plus' to reduce corticosteroid consumption. In an open, single-centre, randomized, controlled study, patients with mild to moderate AD (Severity scoring of AD [SCORAD] score 20-30) were randomized 1:1 to apply the Emollient 'plus' twice daily for 28 days or to continue with their usual classical emollient (Control group). In addition, each patient received topical corticosteroids to use when necessary and according to the dermatologist's prescription. Assessments included SCORAD, PO-SCORAD, local SCORAD, quality of life questionnaires, and tolerability. A total of 119 patients were included in the PP population with a mean age of 26.50 ± 17.5 years old (min-max 3-71 years). Between baseline and day 28, the mean amount of corticosteroid used was lower for the Emollient 'plus' versus Control group (6.03 vs. 9.16 g; p=0.041) and corticosteroid was applied on fewer days (37.5% vs. 46.9% of days; p=0.0256) with fewer applications per day (0.55 vs. 0.71 applications per day; p=0.0203). Similar improvements were observed in both groups for SCORAD, PO-SCORAD, local SCORAD, skin sensation score, AD burden scale, patient benefit index >1, as well as subject and investigator efficacy and tolerability questionnaire assessments. Between baseline and day 28, there was significant corticosteroid-sparing in the Emollient 'plus' group compared to the Control group in quantity, number of applications per day and number of days of use, whilst efficacy was maintained with no significant differences between the two groups for all clinical evaluations, as well as for tolerability.

Burden of adult atopic dermatitis and unmet needs with existing therapies

ObjectivePatients with atopic dermatitis (AD) have low treatment satisfaction. In this study, we evaluated the humanistic burden, treatment satisfaction, and treatment expectations in patients with AD in the United States.MethodsAdults with AD recruited through the National Eczema Association and clinical sites completed a web-based survey comprising the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Dermatology Life Quality Index; Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis; Treatment Satisfaction Questionnaire for Medication (TSQM); and answered questions on healthcare provider (HCP) visits, treatment history, and treatment goals. Descriptive analyses were performed to compare participants by severity.ResultsAmong 186 participants (mean [standard deviation] age 39.7 [15.3] years, 79.6% female), 26.9%, 44.6%, and 26.3% of the participants had mild, moderate, or severe AD, respectively, based on PO-SCORAD. Greater disease severity was associated with a greater impact on work and daily life, decreased TSQM scores, and increased HCP visits. Corticosteroid topical cream or ointment (53.8%) and oral antihistamines (31.2%) were most commonly used for the treatment of AD. Participants reported declining/stopping/changing AD treatment due to the potential for side effects or lack of efficacy. ‘Leading normal lives’ (28.0%) and ‘being itch-free’ (33.9%) were important treatment goals.ConclusionsIndividuals with AD, especially severe disease, face a considerable humanistic burden even while using treatment.

Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin

Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited. In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects. Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14days. Punch biopsy specimens were collected for biomarker analysis at baseline from all participants, then from AD patients only at day 8 (optional) and day 15. Compared to the vehicle, crisaborole significantly reversed dysregulation of the overall lesional proteome and of key markers and pathways (eg, Th2, Th17/Th22, and T-cell activation) associated with AD pathogenesis toward both nonlesional and normal skin. Significant clinical correlations were observed with markers associated with nociception and Th2, Th17, and neutrophilic activation. Study limitations include predominance of white patients in the cohort, relatively short treatment time, and regimented administration of crisaborole. Our results demonstrate crisaborole-induced normalization of the AD proteome toward a nonlesional molecular phenotype and further support topical PDE4 inhibition in the treatment of mild to moderate AD.

Influence of the cream with filaggrin activity modulator for dry and sensitive skin in children with mild to moderate severity atopic dermatitis on objective indicators of skin barrier function and disease severity indices

BACKGROUND: Atopic dermatitis is a chronic, relapsing and severely itchy dermatitis that usually occurs in childhood and has a characteristic age-related distribution. Atopic dermatitis is relatively frequent, affecting 1020% of children in developed countries. Atopic dermatitis in children associated with poor school performance, low self-esteem and family problems. Recent studies show importance in atopic dermatitis pathogenesis of protein filaggrin and modulation of its activity may be a promising direction in the pathogenic therapy of atopic dermatitis.&#x0D; AIM: to study the effect of a cream for dry, sensitive and atopic skin with a modulator of filaggrin activity on the course of mild and moderate atopic dermatitis.&#x0D; MATERIAL AND METHODS: An open, prospective, multicentre, non-comparative, single-group clinical trial was organized to test the effectiveness of a cream with a filaggrin activity modulator. The study was on outpatients in the participated centers and included 5 visits with a screening visit 1, and 5th visit ― therapy completion. Cream was used for 12 weeks. In total, the study involved 60 children aged 3 to 18 years with diagnoses of atopic dermatitis of mild and moderate severity. The severity of atopic dermatitis was measured with the SCORAD, EASI, IGA scales, also measured was skin pH and transepidermal water loss (TEWL), as well as the severity of xerosis according to visual analogue scale.&#x0D; RESULTS: The severity of atopic dermatitis in children whose therapy regimens included Admera cream decreased by 19.6 points according to the SCORAD index, including in children who did not receive mometasone furoate in the therapy schemes, the SCORAD index decreased statistically significantly compared to the baseline data (p 0.001). The overall decline in the EASI index ― by 3.0 points, the IGA global assessment index ― by 2.0 points, the severity of xerosis decreased by 3 points (in all cases, p 0.001). Transepidermal water loss decreased (by 4.5 g/m2 per hour, p 0.001); Skin pH did not change (difference 0.02, p=0.34). The smell was rated as "excellent" by 86.7% (95% CI 75.494.1), the consistency ― by 83.3% (95% CI 71.591.7) of the respondents, and overall satisfaction was noted by ― 88.3% (95% CI 77.495.2) of the respondents.&#x0D; CONCLUSION: Сream for dry and sensitive skin with a modulator of filaggrin activity during the study showed good efficacy and tolerability and can be used in atopic dermatitis treatment regimens as a basic care product, both during exacerbation and remission.

Application of noninvasive hardware technique of transcranial electrical stimulation (TES) in patients with atopic dermatitis

BACKGROUND: Transcranial electrostimulation (TES therapy) is a physiotherapeutic non-invasive technology that allows painlessly, selectively and strictly dosed activation of certain brain structures producing endogenous opioid peptides by modulating activity in these brain regions that are involved in the processing of pain and itching signals. Originally, this technique was used as an electronarcosis, then the scope of TES therapy in medicine expanded and began to be used in neurology, gynecology, urology, gastroenterology. The efficacy of its use in dermatology as an antipruritic action remain poorly understood.&#x0D; AIM: the purpose of the pilot study was to evaluate the effectiveness and acceptability of the use of non-invasive TES therapy in patients with atopic dermatitis.&#x0D; MATERIAL AND METHODS: According to the existing concept, itching is considered as a kind of pain sensation caused by an altered threshold level of nerve endings in the skin that perceive pain. Given this similarity of the mechanisms of pain and itching, noninvasive brain stimulation can simultaneously reduce itching, which opens up broad prospects for its further use in itchy dermatoses.&#x0D; A pilot controlled study was conducted, the object of the study was patients with moderate atopic dermatitis (9 women and 6 men) aged 19 to 48 years. TES therapy was carried out by a pulsed bipolar electrical stimulator with acoustic effect "TRANSAIR-07" according to the standard method. All patients who received a course of TES monotherapy underwent 10 procedures, 1 time a day, lasting 3040 minutes, with a current of 13 mA. To assess the dynamics of clinical manifestations of atopic dermatitis and the severity of the disease, the following scales were used: SCORAD, EASI, IGA, DLQI, HADS, BDI. The assessment was carried out twice: the first time on the day of diagnosis verification and again on the 10th day of treatment.&#x0D; RESULTS: As a result of the treatment, there was a decrease in itching from 5 to 2 points, an improvement in mood from 5 to 1 point, an increase in performance from 4 to 1 point, a decrease in anxiety and depression from 4 to 2 points. With a general assessment of the dynamics of the indicators of the applied clinical scales (SCORAD, EASI, IGA, DLQI, HADS, BDI), the total average effectiveness in the form of parameter improvement amounted to 66.25% reduction by the end of the 10-day course.&#x0D; CONCLUSION: The work presents the modern aspects of the application of non-invasive hardware transcranial electrical stimulation technique. The positive results of our own pilot study are presented and data confirming the clinical efficacy of transcranial electrical stimulation in patients with atopic dermatitis are presented, which determines the prospect of developing a combined application of TES therapy for this persistent disease.

Implications of Atopic Dermatitis on the Quality of Life of 6-11 Years Old Children and Caregivers (PEDI-BURDEN).

Atopic dermatitis (AD) is a chronic, relapsing and remitting inflammatory skin disease characterized by intense itch. The disease burden includes physical limitations, psychosocial discomfort, and a reduced quality of life (HRQoL). This study presents the results of a parent-reported survey on the psychosocial impact of AD on Italian pre-adolescent children (6-11 years old), with a specific focus on bullying, self-isolation, absenteeism, and presenteeism. An online questionnaire was sent to 3067 random recipients and 160 matched the inclusion criteria for age, self-reported AD diagnosis, localizations (according to ISAAC), and disease severity (POEM ≥8). 100 children, with comparable ages, not matching the inclusion criteria for AD, were recruited as a control group. Children with AD and their caregivers had a significantly lower quality of sleep (QoS) compared to the control group. The presence of AD was directly responsible for many restless nights, both in children and caregivers (58.9 and 55.4 respectively). Children with AD and their parents also experienced significantly more daytime drowsiness (43.6 and 54.6 days, respectively). Children with AD were more frequently victims of bullying at school (20.0% vs 9.0%; p≤0.05) or in other social environments (16.9% vs 3.0%; p≤0.05). AD caused 17.7 days of absenteeism and 20.1 days of presenteeism per student over the previous 12 months, accounting for 37.8 days of study impairment overall. Severe/very severe AD had a significantly greater impact on presenteeism than moderate AD (25.1 vs 17.5 days; p≤0.05). Presenteeism, which was more pronounced among bullied students, was positively correlated with absenteeism only in the AD cohort. AD has a detrimental impact on the HRQoL of pediatric patients, causing stigmatization and social isolation. Functional distress was also reported by caregivers. Our study might inform the public and policymakers about the disease burden of AD at a young age.

Effectiveness and safety of dupilumab in adults with moderate and severe atopic dermatitis in Colombia: Real-life experience

BackgroundDupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effectiveness and safety of dupilumab in adults with moderate to severe AD in a Colombian multicenter cohort. MethodsMulticenter descriptive study that included patients who started treatment between March 2018 and May 2020 in 6 centers. Disease severity was assessed using the following: Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). These measurements were collected according to availability at baseline, 3–5 months, 6–12 months, and more than 12 months. Days of sick leave, hospitalizations, and AD flares before and after dupilumab treatment were reported. Adverse events (AEs) were recorded during follow-up. ResultsNinety-three patients were included, with a median age of 32 years (IQR: 24.0; 40.0) and a disease evolution time of 21 years (IQR: 16.0; 29.5). 88.2% had at least 1 allergic disease other than AD. An improvement greater than or equal to 75% EASI was observed in 41.7% of patients at 3–5 months, in 73.7% of patients at 6–12 months, and in 75.0% of patients after 12 months. For those reporting SCORAD and POEM, the median percent change ([IQR], n) from baseline in SCORAD was −67.1 ([−79.2; −54.2], n = 16), −70.5 ([−85.8; −47.9], n = 36) and −66.7 ([−77.3; −51.0], n = 13); and POEM, −58.6 ([−66.4; −55.5], n = 4), −73.0 ([−86.5; −66.7], n = 16) and −87.3 ([−93.4; −69.6], n = 8), respectively. Before initiation of dupilumab treatment, 82 (88.2%) patients reported at least 1 flare of AD in the past 12 months. During the follow-up period, 30 (32.3%) patients reported at least 1 exacerbation or flare. Twelve patients (12.9%) presented an AE and 3 (3.2%) patients discontinued dupilumab for this cause. ConclusionsDupilumab was effective and safe for the treatment of moderate to severe AD in point-of-care settings, with results similar to randomized controlled and other real-life studies. These positive results are still maintained even though a high number of patients had short interruptions in the use of dupilumab due to administrative problems.

Understanding Flares in Pediatric and Adolescent Patients with Moderate or Severe Atopic Dermatitis: A Real-world Study in the United States and Europe

Understanding Flares in Pediatric and Adolescent Patients with Moderate or Severe Atopic Dermatitis: A Real-world Study in the United States and Europe