Moderate Atopic Dermatitis Research Articles

Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3. Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved. Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin. Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.

Patient and Parent/Caregiver Satisfaction with Efficacy and Cosmetic Elegance of Tapinarof Cream 1% Once Daily in a Long-term Extension Trial in Adults and Children Down to Age 2 Years with Atopic Dermatitis

Introduction: Patients with atopic dermatitis (AD) report low satisfaction with currently available topical therapies. Satisfaction and patient preference are closely linked to treatment adherence, and understanding preferences may contribute to improving the quality of AD care and adherence. In the pivotal 8-week, phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated superior efficacy versus vehicle and was well tolerated in adults and children down to age 2 years with AD. We report Patient Satisfaction Questionnaire© (PSQ) results from ADORING 3, a 48-week, open-label extension trial. Methods: In ADORING 3, eligible patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet inclusion criteria for ADORING 1 or 2, were followed for up to 48 weeks. The PSQ was completed at Week 48 or at early termination visit and assessed patient or parent/caregiver satisfaction with tapinarof efficacy, cosmetic elegance (look and feel of tapinarof cream), application ease, impact on daily life, and preference for tapinarof versus prior AD therapies. Patients aged ≥16 years self-completed the PSQ; parents/caregivers completed for children aged 2 to 15 years. Results: 505 patients or parents/caregivers completed the questionnaire. Respondents consistently reported high rates of satisfaction across all parameters. Most patients or parents/caregivers strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (91.5%), quick absorption (89.5%), application ease (97.6%), impact on daily life (94.3%), efficacy (92.3%), and confidence in tapinarof (92.7%). For patients or parents/caregivers who reported prior use of other topical therapies to treat AD, most strongly agreed or agreed that tapinarof was more effective (86.3%), easier to use (68.6%), and that they preferred tapinarof to prior topicals (88.0%). Compared with systemic drugs used previously for AD, most strongly agreed or agreed that tapinarof was more effective (84.6%), easier to use (77.6%), and that they preferred tapinarof to prior systemic drugs (85.9%). Conclusion: Patient or parent/caregiver satisfaction data from ADORING 3 showed a consistent and highly positive perception of long-term use of tapinarof cream across all parameters, including satisfaction with tapinarof efficacy, cosmetic elegance, application ease, impact on daily life, and preference for tapinarof compared with prior AD therapies. Satisfaction with tapinarof is likely to contribute to long-term adherence and improved outcomes for patients with AD.

JANUS KINASE INHIBITOR IN COMBINATION THERAPY IN ATOPIC DERMATITIS

BACKGROUND: Atopic dermatitis (AD) is a chronic recurrent immunoinflammatory skin disease that develops against the background of a genotypic defect in the skin barrier function and innate and adaptive autoimmunity. Currently, there is no specific therapy for AD, so there remains a need to constantly search for effective pathogenetic approaches to its treatment. Today, the Janus kinase type 1 inhibitor abrocitinib is recommended for the treatment of moderate to severe AD. AIMS: to conduct a comparative assessment of the effectiveness of the combination of UVB 311 nm with abrocitinib and UVB 311 nm phototherapy against the background of standard therapy according to indications in the treatment of patients with moderate and severe atopic dermatitis. MATERIALS AND METHODS: During the period from 2023 to 2024, the dermatological status and quality of life were assessed in 40 patients with moderate to severe atopic dermatitis who were prone to frequent relapses. The patients were treated at the clinic for skin and venereal diseases. Depending on the therapy, all patients were divided into two groups. The first group consisted of 20 patients receiving systemic, topical therapy in combination with UVB 311 phototherapy and additionally abrocitinib, at an induction dose of 200 mg followed by a dose of 100 mg. The second group included 20 patients who received systemic, local therapy in combination with UVB 311 phototherapy. Upon admission to the hospital and after two months of therapy, a comparative assessment of the DLQI index and an assessment of the prevalence and intensity of skin lesions in accordance with the SCORAD and IGA index were performed, an assessment of the level of IgE in the blood were performed RESULTS: after the course of therapy, the SCORAD index in patients of the first and second groups decreased statistically significantly (p=0.001) by 2.4 times and 1.6 times, respectively. The DLQI index in patients of the first and second groups after the course of therapy significantly (p=0.001) decreased by 3.2 times, 2.1 times, respectively. CONCLUSIONS: Our study revealed a more significant effectiveness of therapy with abrocitinib in combination with UVB 311 compared with UVB 311 monotherapy in patients with moderate and severe atopic dermatitis.

Atopic Dermatitis-Related Problems in Daily Life, Goals of Therapy and Deciding Factors for Systemic Therapy: A Review

Background/Objectives/Methods: Atopic dermatitis (AD) impacts various aspects of patients’ lives including personal life, psychological aspects/disturbances (e.g., depression, anxiety, or even suicidal thoughts), school, and work-related activities, including career advancement. The aim of this narrative review is to present the latest information available on how to best approach AD patient management, as well as decisions regarding standard/advanced systemic therapy, by gathering evidence from the relevant medical literature (PubMed and other prominent medical databases). Results: Thus, AD patient management and decisions regarding advanced/systemic therapy are complex, requiring the consideration of multiple disease-related factors: age; disease severity; patient medical history and comorbidities; previous topical therapy use and any adverse reactions; treatment efficacy concerns; patient preferences, expectations and fears; pregnancy planning; ability and willingness to adhere to the treatment regimen; impact on related risks; and any associated psychological or psychiatric issues. Current guidelines and systematic reviews support the safety and efficacy of systemic therapy including conventional drugs (cyclosporine, methotrexate, and azathioprine), biologics (dupilumab and tralokinumab), and JAK inhibitors (baricitinib, upadacitinib, and abrocitinib) recommended for treating moderate and severe AD. Recently, additional biologics have been evaluated in clinical trials, including lebrikizumab, nemolizumab, eblasakimab, and OX40/OX40L, among others. Conclusions: The most recently suggested approach to treating AD patients suggests focusing on therapy that targets and achieves minimal disease activity (MDA), where therapy decisions are informed by both the patient and the clinician. Available data also indicate the importance of a personalized, stepwise, and multidisciplinary approach. This type of approach promotes patient compliance, satisfaction with therapy, and increased engagement, which all lead to better patient outcomes.

Pimecrolimus Efficacy and Safety in Management of Children with Atopic Dermatitis

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Early management of AD is crucial for preventing the development of atopic disease such as asthma, allergic rhinitis, etc. Topical glucocorticoids (TGCs) are used as first-line therapy, however, their long-term use poses the risk for patient's health. Despite the rapid clinical response at skin process aggravation, long-term use of TGCs in first-line therapy is associated with various adverse events, including: skin atrophy, hypothalamic-pituitaryadrenal axis suppression, telangiectasis, etc. All together it limits the long-term TGCs use, especially in management of pediatric patients and using such drugs in sensitive regions such as face and intertriginous areas. Due to these limitations TGCs should only be used for a short period of time. Thus, limitations in both treatment duration and number of drugs make TGCs non-optimal for long-term AD treatment. Pimecrolimus (1% cream) is a topical calcineurin inhibitor that is indicated for the treatment of mild to moderate AD. Pimecrolimus does not cause any significant side effects compared to TGCs and it is well tolerated for long-term administration.

Unveiling the Impact of Moderate and Severe Atopic Dermatitis: Insights on Burden, Clinical Characteristics, and Healthcare Resource Utilization in Adult Greek Patients from the APOLO Cross-Sectional Study.

Background: Moderate to severe (M2S) atopic dermatitis (AD) is a chronic condition impacting individuals, society, and healthcare systems. Considering the changing M2S-AD treatment landscape, this study assesses the M2S-AD burden in patients reaching referral centers in Greece. Methods: This was a multicenter, cross-sectional study. Patients aged 12 years or older with clinically diagnosed M2S-AD were enrolled. Data collected included clinical practice assessments and the following validated patient-reported instruments: Dermatology Life Quality Index (DLQI); EuroQol-5 Dimensions-3 Level scale (EQ-5D-3L); Patient Oriented Eczema Measure (POEM); Peak Pruritus Numerical Rating Scale (PP-NRS); and Work Productivity and Activity Impairment: General Health (WPAI:GH). A pain frequency/intensity/cause questionnaire and a sleep disturbance scale were also used. Results: Outcomes of 184 adults (51.1% female) with M2S-AD based on the Eczema Area and Severity Index (EASI) are presented (n = 117 moderate; n = 67 severe). Among the patients, 14.8% were obese, 59.2% had allergic comorbidities, and 88.0% were receiving AD-specific therapy (systemic: 38.6%). The median age, disease duration, body surface area, and total EASI scores were 38.8 years, 11.8 years, 30.0%, and 16.9, respectively. The median DLQI score was 12.0, with 'symptoms/feelings' being the most affected domain. EQ-5D dimensions 'anxiety/depression' and 'pain/discomfort' were also affected (65.2% and 64.1% reporting problems, respectively). The median POEM score was 17.0. Pain, severe pruritus (PP-NRS ≥ 7), and sleep disturbance were reported by 80.4%, 62.0%, and 88.5%, respectively. The median WPAI:GH 'work productivity loss' and 'activity impairment' scores were 23.8% and 30.0%, respectively. Conclusions: Both moderate and severe AD patients reaching Greek specialized centers experience significant symptom burden and impairments in quality of life, sleep, work, and daily activities.

Natural Skin Care Regimen Improves Clinical Parameters and Quality of Life in Children with Atopic Dermatitis

Background: Atopic dermatitis (AD) is a prevalent, chronic inflammatory skin disorder, characterized by xerosis, itching and recurrent eczematous lesions. The condition also has major psychosocial implications for patients and their families. A daily skincare regimen of gentle cleansing and moisturization is an important part of atopic dermatitis therapy. Objective: This study evaluated the tolerability and efficacy of a nature-based shampoo/wash and moisturizer in children with mild to moderate atopic dermatitis Methods: This open-label study involved 23 children (6 months – 13 years) with atopic dermatitis. A daily skin care regimen of nature-based shampoo/wash and moisturizer was used for 4 weeks. The primary endpoint was tolerability assessed through clinical grading of erythema, dryness and roughness. The study pediatrician graded the eczema condition using the Eczema Area and Severity Index (EASI), and assessments of stratum corneum hydration and transepidermal water loss were performed before and after treatment. Parent/guardian completed two validated quality of life questionnaires. Results: Twenty children completed the study. Clinical evaluations showed significant improvement in subjects’ atopic disease with daily use of nature-based regimen. Significant reduction in dryness and roughness was observed, indicating that both products were well-tolerated. Moisture content and transepidermal water loss measurements showed directional improvements in skin barrier function. Parent/guardian reported significant improvements in quality-of-life assessments. Conclusions: The study demonstrated that nature-based skin care regimen was well tolerated and improved quality of life and skin condition in children with atopic dermatitis and can be used either alone or in adjunction with traditional treatment for disease control.

Severe exacerbation of facial dermatitis with swelling following introduction of abrocitinib in a patient with atopic dermatitis

BackgroundAbrocitinib, an oral small-molecule Janus kinase 1 (JAK1) inhibitor, has been widely accepted for the treatment of moderate-to-severe atopic dermatitis (AD). Currently there is a paucity of data on the adverse events (AEs) after abrocitinib treatment, especially on rare events such as exacerbation of facial dermatitis, and their causal relationship and subsequent management remains poorly elucidated.Case presentationA 43-year-old female patient with moderate AD received dupilumab after failure of topical treatments. Facial dermatitis persisted and became refractory after dupilumab treatment, and the patient changed treatment to oral abrocitinib. Fifteen hours after the first dose of abrocitinib, she developed exacerbation of facial dermatitis with swelling. The patient was initially diagnosed as abrocitinib-induced hypersensitivity. However, a score of 3 of the Naranjo adverse drug reaction assessment indicates week correlation between abrocitinib therapy and exacerbation of facial dermatitis, and negative results from subsequent drug provocation test further suggests no causal relationship.ConclusionsThe present case report highlights the necessity of careful determination of abrocitinib-induced hypersensitivity, which should not be diagnosed simply based on the time sequence between drug exposure and symptom occurrence. In addition, caution should be exercised for drug withdrawal, especially when confirmative evidence is absent. Drug provocation test can be helpful and effective treatments could be continued unless severe AEs occur.

Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children

Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates. To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD. Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]). Patients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks. The primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated. Among 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P < .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P < .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P < .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P < .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site. In 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability. ClinicalTrials.gov Identifiers: NCT04773587, NCT04773600.

Roflumilast cream (Zoryve) for atopic dermatitis.

The FDA has approved a 0.15% cream formulation of the phosphodiesterase-4 (PDE4) inhibitor roflumilast (Zoryve – Arcutis) for topical treatment of mild to moderate atopic dermatitis (AD) in patients ≥6 years old. Roflumilast is the second PDE4 inhibitor to be approved in the US for treatment of AD; crisaborole (Eucrisa), which can be used in patients ≥3 months old, was the first.

Prospective Clinical Study: Full-Body Blue Irradiation in the Treatment of Atopic Dermatitis.

Ultraviolet-free (UV-free) blue light phototherapy has emerged as a promising option due to its reported efficacy and minimal adverse effects. This study aims to evaluate the effectiveness of full-body blue light irradiation in both adult and pediatric patients with atopic dermatitis (AD), assessing its impact on skin condition and mood regulation by investigating serum concentrations of serotonin and kynurenine pathway metabolites. 20 patients (age 9-45) with moderate and severe AD were included in the study. Treatment consisted of 10 irradiations with Full Body Blue device (453nm). Serum concentrations of serotonin, quinolinic acid, kynurenic acid, tryptophan, and kynurenine were measured before and after irradiations. After 10 sessions of full blue light therapy (453nm) statistically significant improvements were observed in Eczema Area Severity Index (EASI 13.16 vs. 8.65; p = 0.00016), SCORing Atopic Dermatitis (SCORAD 44.99 vs. 23.73; p < 0.00001), Visual Analogue Scale (VAS 6.53 vs. 3.95; p = 0.00251), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001). Moreover, statistically significant decrease in Dermatology Life Quality Index (DLQI) was noted (14.37 vs. 7.42; p = 0.00351). Additionally, increase in the serum concentration of serotonin was observed after completing 10 irradiation sessions (median 139.77mg/ml vs. 274.92mg/ml; p < 0.00001). Blue light may be a promising and safe treatment in patients with AD. It might also positively influence mood. Further investigations are needed to confirm those findings. ClinicalTrials.gov identifier, NCT06516783.

Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.

Oral Janus Kinase Inhibitors in Pediatric Atopic Dermatitis.

To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi'sabrocitinib (ABRO),baricitinib(BARI), andupadacitinib (UPA),are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10years with moderate-to-severe AD. Fortunately,majorsafety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred.There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.

Efficacy and Safety of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A Meta-Analysis.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder. Topical corticosteroids are the cornerstone of therapy in mild AD, whereas the JAK inhibitor upadacitinib is approved in the United States, Europe, and other countries for treating moderate-severe AD in adults and children over 12 years old whose disease is not adequately controlled with other systemic drugs, including biologics. The objective of this meta-analysis was to assess the overall efficacy and safety of upadacitinib in moderate to severe AD. All randomized controlled trials (RCTs) evaluating the efficacy and safety of upadacitinib in moderate to severe AD were included in the meta-analysis. The pooled analysis revealed a significant proportion of patients achieving Eczema Area and Severity Index-75 (EASI 75) (R.R. = 3.86; 95% CI = 3.12 to 4.78, p < 0.00001), EASI 100 (R.R. = 13.09; 95% CI = 7.40 to 23.17, p < 0.00001), Worst Pruritus Numerical Rating Score (WP-NRS) response (R.R. = 4.44; 95% CI = 3.72 to 5.29, p< 0.00001), and validated Investigator's Global Assessment (v-IGA) (RR = 5.96; 95% CI = 4.79 to 7.41, p < 0. 00001) in the upadacitinib arm compared to the placebo arm. Moreover, the pooled analysis also suggested that treatment-emergent adverse events (TAEs) were relatively higher with upadacitinib than with placebo, but were mild and easily manageable (R.R. = 1.15; 95% CI = 1.09 to 1.23, p<0.00001). This meta-analysis showed that upadacitinib had a significant beneficial effect and tolerable adverse effect profile in patients with moderate and severe AD. Dose regimens of 15 mg and 30 mg seemed to have similar benefits. However, further trials are needed to assess long-term efficacy and safety profile.

Ruxolitinib Cream in Adolescents/Adults with Atopic Dermatitis Meeting Severity Thresholds for Systemic Therapy: Exploratory Analysis of Pooled Results from Two Phase3 Studies.

Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52weeks was assessed in a subset of patients with moderate and/or more extensive disease. This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigator's Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed. Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period: 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week8 (continuous-use), IGA-treatment success (IGA0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use: week8) to 18/23 patients (78.3%; as-needed use: week52) in patients applying ruxolitinib cream from day1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population. Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy. NCT03745638/NCT03745651.

Atopic Dermatitis and Abrocitinib: Unraveling the Therapeutic Potential

Abstract: Atopic dermatitis (AD) is a chronic immune-mediated skin condition seriously affecting both children and adults and impacting their quality of life. This complex condition involves genetic predisposition, immune system impairment, and environmental factors. The Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway plays a key role in AD pathogenesis and progression. Abrocitinib presents a hopeful avenue for managing moderate to severe AD, offering significant symptom relief and potential long-term benefits. Its targeted approach to modulating the JAK-STAT pathway holds promise for improved AD management. This comprehensive review explores AD pathogenesis, the chemistry and clinical pharmacology of Abrocitinib, and its safety and efficacy in various trials.

Combination of a Topical Anti-Inflammatory Drug and a Moisturizer, Both with a Lamellar Structure Containing Synthetic Pseudo-Ceramides, for the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis.

Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis. We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period. Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function. These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function.

Effectiveness of a nurse-led one-to-one education programme in addition to standard care in children with atopic dermatitis: a multicentre randomized control trial.

Therapeutic patient education (TPE) is recommended for children with atopic dermatitis (AD), but no consensus has been reached on the optimal tailoring of delivery. While repeated multidisciplinary group education sessions have shown effectiveness, the benefits of one-on-one educational interventions led by nurses for children with AD have not yet been assessed. To assess the benefits of additional, well-structured, 1-h nurse-led individual TPE interventions in children with AD and their families compared with standard care alone. Children with moderate-to-severe AD and their parents were randomized to receive a 1-h nurse-led education session in addition to standard care vs. standard care alone. The primary outcome was the area under the curve (AUC) of the SCORing of Atopic Dermatitis index (SCORAD) from baseline to week 24 (lower AUC values represent better long-term control of the disease). In our study, 176 patients were randomized across 11 centres, and 153 were included in the full analysis set. The mean (SD) age was 4.47 (4.57) years. By week 24, there were no significant differences in the AUCs of the SCORAD between the two groups (P = 0.3). Secondary outcomes including patient-reported severity and quality of life [AUCs of the patient-oriented SCORAD (PO-SCORAD) and Infants' Dermatitis Quality of Life Index (IDLQI), Children's Dermatitis Quality of Life Index (CDLQI) and Family Dermatitis Quality of Life Index (FDLQI)] were not significantly different between the two groups. The only significant change observed in the intervention group, when compared with the one receiving standard care, was a decrease in topical steroid phobia, as assessed by the topical corticosteroid phobia (TOPICOP) score. Prespecified subgroup analyses showed that disease severity in the intervention group was significantly lower throughout the study, compared with the standard-care group when participants had moderate AD at baseline (n = 47); while participants with severe AD at baseline (n = 106) did not show benefit from the intervention. Participants showed no additional benefit from the intervention regardless of age group. This study did not show any additional effectiveness, in long-term severity control, of a 1-h nurse-led TPE intervention in children with AD treated with standard care, compared with those treated with standard care alone. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for patients in the subgroup with moderate AD.

Efficacy and Safety of Dupilumab in Chinese Elderly Patients with Atopic Dermatitis: A Real-World Study

Introduction: With the aging of the population in China, the prevalence of atopic dermatitis (AD) is high in elderly patients. These patients usually have more comorbidities and they need more effective and safer treatments. Dupilumab is an anti-interleukin-4 (IL-4) receptor monoclonal antibody which was approved for the treatment of moderate-to-severe AD. Methods: Elderly patients (60 years or older) with moderate-to-severe AD who treated with dupilumab were included. Eczema Area and Severity Index (EASI) score, Peak Pruritus Numerical Rating Scale (PP-NRS), EASI-50, EASI-75, and EASI-50 were evaluated. The efficacy in subgroups was also investigated. Results: Fifty-eight patients were enrolled. The EASI score and PP-NRS score were significantly reduced at weeks 4, 16, 28, and 52. 91.2% and 79.4% of the patients achieved EASI-50 and EASI-75 at week 16, respectively. 95.8% and 87.5% patients achieved EASI-50 and EASI-75 at week 52, respectively. Adverse events were reported in 10 (17.2%) patients, and no severe adverse event was reported. Male, older age, and moderate AD (EASI <21) were related to better efficacy. Conclusions: This study demonstrated that dupilumab is effective and safe in elderly patients with AD.

Transcranial electrical stimulation (TES) in patients with atopic dermatitis

BACKGROUND: Atopic dermatitis is the most common diseases in dermatology, among the main pathogenetic mechanisms of development of which a complex interaction of a genetically determined defect in the barrier function of the skin, an overactive state of the immune system is considered, and a neurogenic theory of disease development is not excluded, which is based on the relationship of anxiety-stress reactions and neuropsychiatric stresses with the occurrence of pathological changes on the skin. Modern atopic dermatitis therapy is characterized by the appointment of a large number of medications according to clinical recommendations, and the associated increase in allergic and toxic-allergic reactions dictates the need to search for new non-drug treatments for this disease. In order to prevent the pathological effects of stress, as well as to increase resistance to its damaging effects, activation of opioidergic mechanisms may be useful. AIM: To evaluate the effectiveness and acceptability of the transcranial electrical stimulation technique in patients with atopic dermatitis. MATERIALS AND METHODS: A controlled study was conducted among 60 patients with moderate atopic dermatitis, 33 women (55.0%) and 27 men (45.0%) aged 19 to 72 years. Transcranial electrical stimulation was carried out by a pulsed bipolar electrical stimulator with an acoustic effect "TRANSAIR-07", stimulation was carried out by an electric current with a frequency of 77.5 Hz and a duration of 3.5 ms. Patients underwent 10 procedures, 1 time a day, lasting 30 minutes, with a current of 1−3 mA. SCORAD, EASI, IGA, DLQI, HADS, and BDI scales were used to assess the dynamics of clinical manifestations. The assessment was carried out on the first and last day of treatment. RESULTS: During statistical data processing, when comparing the scales in the first and last days of the procedures, depending on the patient groups: the 1st group was the main one, received transcranial electrical stimulation treatment in combination with therapy, according to clinical recommendations, the 2nd group was the control group, received treatment according to clinical recommendations, without the use of transcranial electrical stimulation, significant improvement of itching indicators, clinical manifestations and improvement of quality of life after 4 weeks of therapy in both groups. A statistically more significant dynamics of the indicators of the main clinical scales in favor of combination therapy was established: according to the SCORAD scale ― in the main group from 47.50±2.25 to 21.00±1.00, in the control group from 47.00±2.00 to 39.00±1.75; DLQI ― in the main group from 8.00±2.00 to 2.00±0.75, in the control group ― from 8.50±1.50 to 5.00±1.00. CONCLUSION: The paper presents the positive results of our own research and presents data confirming the clinical effectiveness of transcranial electrostimulation in patients with atopic dermatitis compared with the traditional drug treatment of this disease, which allows us to recommend the treatment regimen we have proposed for widespread implementation in the practice of a dermatovenerologist.