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Introduction: Patients with moderate-to-severe atopic dermatitis (AD) who are most likely to respond to the Janus kinase (JAK) 1/2 inhibitor baricitinib (BARI) are known to have an impacted body surface area (BSA) ≤ 40% and severe itch (numerical rating scale [NRS] ≥ 7], collectively termed 'BARI itch-dominant' patients. Our objective is to build on our previous work by providing a body region-specific, clinical characterization of the BARI itch-dominant patient at baseline and their response to BARI 4 mg. Methods: BREEZE-AD7 was a phase 3 trial in adults with moderate-to-severe AD receiving placebo or 2 mg or 4 mg BARI in combination with topical corticosteroids. Assessing only data from BARI itch-dominant patients, we summarized the baseline characteristics and conducted body region-specific analyses on Eczema Area and Severity Index (EASI) data in order to report the response to placebo versus BARI 4 mg within this patient subtype. Results: BARI 4 mg was highly effective across all body regions; at week 16, 75% improvement was seen in EASI scores (EASI75), and response rates with BARI 4 mg (head/neck, 58.3%; trunk, 69.2%; upper extremities, 61.5%; lower extremities, 87.5%) all exceeded those with placebo (head/neck: 37.5%; trunk, 40.6%; upper extremities, 18.8%; lower extremities, 40.6%) as well as the overall EASI75 rates of the intent-to-treat (ITT) population (BARI, 48.0%; placebo, 23.0%). At baseline, most BARI itch-dominant patients presented with involvement of all regions (mean regional BSA 22.7%–40.3%), highest in the head and neck, mean EASI region scores of 15.7–24.0, and considerably severe sign ratings (mean EASI sub-scores: 1.4–2.3, out of 3), especially for erythema. Conclusion: BARI itch-dominant patients exhibit AD involvement across all body regions and considerable sign severity, especially erythema. In response to BARI 4 mg, EASI quickly improved across regions, substantially more so in this subtype than in the ITT population. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by itching and skin barrier dysfunction. Moderate to severe AD is often refractory to first-line topical treatments, and systemic immunosuppressants have been shown to be effective but have significant adverse effects. The paucity of basic treatments has contributed to the development of targeted topical and systemic immunotherapies based on the use of small molecules and biologic drugs which can directly interact with AD pathogenetic pathways. They represent a new era of therapeutic innovation. Additional new treatments are desirable since AD is a heterogeneous disease marked by different immunological phenotypes. This manuscript will review the mechanism of action, safety profile, and efficacy of promising new systemic immunological treatments for AD. Since moderate to severe AD can result in poor quality of life, the development of targeted and well-tolerated immunomodulators is a crucial purpose. The introduction of new pharmacological agents may offer new therapeutic options. However, there is the need to evaluate how "narrow-acting" agents, such as individual interleukin inhibitors, will perform under the safety and efficacy profiles compared with "broad-acting" agents, such as JAK inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks. Methods: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment). Results: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1–2 weeks), increased through weeks 4–6, and were maintained through week 16. Conclusions: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD. Trial Registration: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422. Plain Language Summary: Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients' descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 1–2 weeks. The extent of the improvements increased through weeks 4–6 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Pain is a distinctive burden in atopic dermatitis and recognized as an important and highly prevalent symptom. It is unknown if the presence of atopic disease may sensitize children to adverse pain profiles in the long term. We aimed to assess the impact of early-life atopic dermatitis-like symptoms on pain at 10 years of age. We used data from 1302 and 874 participants of the Generation XXI birth cohort evaluated at 6 and 15 months, respectively, and 10 years. Atopy-like symptoms since birth, including atopic dermatitis, were collected at ages 6 and 15 months by interviewing parents. Pain history in the last 3 months at age 10 was collected from parents and children using structured questionnaires. We computed relative risks (RR) and respective 95% confidence intervals of pain features at age 10 according to each atopic-like symptom at 6 and 15 months. Children whose parents reported atopic dermatitis-like symptoms at 6 months and at 15 months had higher risk of reporting any pain (RR 1.75 [1.15–2.66]) and multisite pain, respectively (RR 1.67 [1.18–2.37]) at 10 years of age. Conclusion: Atopic dermatitis symptoms in early life were associated with a higher risk of pain at age 10, suggesting that potential for sensitization during the first decade of life and highlighting the importance of improving the health care of children with atopic dermatitis is worth investigating. What is Known: • Atopic disorders have been associated with many non-atopic comorbidities, including chronic pain. • Pain and atopic dermatitis share common inflammatory pathways. Inflammation, injury to the skin from scratching, fissures, and intolerance to irritants related to atopic dermatitis can cause pain. What is New: • Atopic dermatitis in early life is linked to an increased likelihood of experiencing pain at the age of 10, which suggests that exploring the potential for sensitization is a worthwhile area of investigation. • Our proof-of-concept study highlights the potential benefit of studying management targets and improving itching and relieving skin pain as quickly as possible, avoiding potential long-term consequences of the sensitization process. [ABSTRACT FROM AUTHOR]

Psychological stress and intestinal leakage are key factors in atopic dermatitis (AD) recurrence and exacerbation. Here, we demonstrate the mechanism underlying bacterial translocation across intestinal epithelial barrier damaged due to stress and further aggravation of trimellitic anhydride (TMA)–induced itch, which remain unclear, in AD mice. Immobilization (IMO) stress exacerbated scratching bouts and colon histological damage, and increased serum corticosterone and lipopolysaccharide (LPS). Orally administered fluorescein isothiocyanate (FITC)-dextran and surgically injected (into the colon) Cy5.5-conjugated LPS were detected in the serum and skin after IMO stress, respectively. The relative abundance of aerobic or facultative anaerobic bacteria was increased in the colon mucus layer, and Lactobacillus murinus, E. coli, Staphylococcus nepalensis, and several strains of Bacillus sp. were isolated from the spleens and mesenteric lymph nodes. Oral antibiotics or intestinal permeability blockers, such as lubiprostone (Lu), 2,4,6-triaminopyrimidine (TAP) and ML-7, inhibited IMO stress-associated itch; however, it was reinduced through intradermal or i.p. injection of LPS without IMO stress. I.p. injection of TAK-242 (resatorvid), a TLR4 inhibitor, abrogated IMO stress-associated itch, which was also confirmed in TLR4-KO mice. IMO stress alone did not cause itch in naïve mice. IMO stress-induced itch aggravation in TMA-treated AD mice might be attributed to the translocation of gut-derived bacterial cells and LPS, which activates peripheral TLR4 signaling. [ABSTRACT FROM AUTHOR]

Pain and itch are recognized as antagonistically regulated sensations; pain suppresses itch, whilst pain inhibition enhances itch. The neural mechanisms at the central nervous system (CNS) underlying these pain-itch interactions still need to be explored. Here, we revealed the contrasting role of orexin-producing neurons (ORX neurons) in the lateral hypothalamus (LH), which suppresses pain while enhancing itch neural processing, by applying optogenetics to the acute pruritus and pain model. We also revealed that the circuit of ORX neurons from LH to periaqueductal gray regions served in the contrasting modulation of itch and pain processing using optogenetic terminal inhibition techniques. Additionally, by using an atopic dermatitis model, we confirmed the involvement of ORX neurons in regulating chronic itch processing, which could lead to a novel therapeutic target for persistent pruritus in clinical settings. Our findings provide new insight into the mechanism of antagonistic regulation between pain and itch in the CNS. The optogenetic approach sheds light on the diametric roles of ORX neurons in processing itch and pain. The neural circuit of ORX neurons from LH to the PAG region plays a crucial part in this bidirectional modulation of itch and pain processing. [ABSTRACT FROM AUTHOR]

Introduction: The 2021 US approval of ruxolitinib cream for treatment of atopic dermatitis (AD) in patients aged ≥ 12 years was based on the results of two pivotal phase 3 studies. Currently, real-world data to describe effectiveness of ruxolitinib cream and physician satisfaction with treatment remain limited. Our objective is to describe disease control among adults with mild to moderate AD prescribed ruxolitinib cream and physician satisfaction with treatment. Methods: Data were from the Adelphi AD Disease Specific Programme™, a US real-world, cross-sectional survey of physician-reported data, undertaken between August 2022 and March 2023. For patients aged ≥ 18 years, physicians reported patient demographics, clinical characteristics, treatment patterns, and physician satisfaction with disease control. Descriptive analysis of data for patients with mild to moderate AD prior to the initiation of ruxolitinib cream and treated with ruxolitinib cream for ≥ 1 month was undertaken. Results: Among physician-reported data from 1360 patients with AD, 149 patients had received ruxolitinib cream (in combination or as monotherapy) for ≥ 1 month, including 59 patients receiving monotherapy. Prior to treatment with ruxolitinib cream, 84.6% of patients had moderate AD (Investigator's Global Assessment, IGA of 3), whereas after treatment (median duration, 26 weeks), only 21.5% had an IGA of 3, with 48.3% of patients having clear or almost clear skin (IGA of 0/1). For these patients, 81.2% were not currently experiencing a flare, and physicians were satisfied with disease control for 87.3%. Results were similar in patients receiving monotherapy. The most frequent physician-reported reasons for prescribing ruxolitinib cream included relieving itch, improving lesion redness/thickness, achieving disease control, and reducing/controlling flares. Conclusions: These real-world findings demonstrate effective disease control and physician satisfaction with ruxolitinib cream for the treatment of AD in adults in a clinical practice setting. Outcomes were similar whether ruxolitinib cream was prescribed as monotherapy or in combination regimens, suggesting a role for ruxolitinib cream across the spectrum of disease. Plain Language Summary: Atopic dermatitis (AD) is a disease in which skin can be itchy, inflamed, and cracked. Traditional therapies for mild to moderate AD can be limited by side effects and long-term safety issues. After US approval of ruxolitinib cream for the treatment of mild to moderate AD in 2021, the goal of this study was to describe disease control and doctor satisfaction with ruxolitinib cream in a real-world setting. The Adelphi AD Disease Specific Programme™ surveyed 159 doctors who treated people with AD between August 2022 and March 2023. Doctors reported records from 1360 patients with mild to moderate AD. In these patients, ruxolitinib cream was used for at least 1 month in 149 patients and was used alone in 59 patients. Before the use of ruxolitinib cream, nearly 85% of the 149 patients had moderate AD. After the use of ruxolitinib cream, about 20% had moderate AD, with half having clear or almost clear skin. About 80% were not currently experiencing flares. Doctors were satisfied with disease control in more than 85% of patients. Patients applying ruxolitinib cream alone had similar results. Doctors most often prescribed ruxolitinib cream for itch relief, disease control, and to reduce or control flares. In summary, when ruxolitinib cream was used by patients, it provided good disease control, and doctors were satisfied with results. Outcomes were similar in patients who applied ruxolitinib cream alone or with another treatment. This suggests that ruxolitinib cream may be useful for patients with AD of differing levels of severity. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the "atopic march" and disrupting the "itch–scratch" cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Clinical Drug Investigation. It discusses the real-world effectiveness and safety of a drug called baricitinib in patients with atopic dermatitis (AD). AD is a chronic inflammatory skin disease that affects both children and adults. Baricitinib is a medication that inhibits certain cytokines involved in AD pathophysiology. The letter describes a retrospective multicenter study conducted in Portugal, which evaluated the effectiveness and safety of baricitinib over a 24-week period in patients with moderate-to-severe AD. The study found that baricitinib showed positive outcomes in terms of reducing AD severity and improving quality of life for patients. No serious adverse events were reported, and the drug was generally well-tolerated. This document discusses the effectiveness and safety of baricitinib, a medication used to treat moderate-to-severe atopic dermatitis (AD). The study found that baricitinib showed similar effectiveness to clinical trials in reducing itch and skin inflammation in patients with AD. Patients who had not received prior treatment with dupilumab, another medication for AD, showed better effectiveness with baricitinib. The study also indicated a favorable tolerability and safety profile for baricitinib. However, further real-world studies with larger patient populations are needed to gather more comprehensive evidence. [Extracted from the article]

Background and Objective: Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2. Methods: This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16. Results: Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%). Conclusions: Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available] Clinical Trial Registration: NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. 6QcTdZHHiWG8xHjHtHEVo6 Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB) [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. Objective: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. Methods: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. Results: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4–6, and 10 were associated with 0 days, 3–4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0–1, 4–5, and 10 were associated with 0–10%, 20–30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. Conclusion: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. Clinical Trial Registration: NCT03575871 Plain Language Summary: Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that bleach baths improve atopic dermatitis (AD) severity; however, the effects on itch, skin barrier, and cutaneous microbial composition are less clear. We examined whether bleach baths reduce itch, normalize skin barrier function, reduce S. aureus absolute abundance, and increase microbial diversity in adults with AD who were colonized with S. aureus on their non-lesional skin. This was an open label, non-randomized, controlled trial performed at a single academic center. Fifteen AD and five non-atopic healthy controls (NA) were instructed to take two bleach baths (0.005% NaClO; 5–10 min duration) per week for a total of 12 weeks as add-on therapy. Adults 18 to 65 years (inclusive) with mild to severe AD were recruited with EASI score > 6.0, S. aureus culture positivity, access to a bathtub, and ability and willingness to maintain current topical or systemic treatments. They were evaluated at baseline (before bleach baths), 6 weeks, and 12 weeks after the intervention of twice-weekly bleach baths. Efficacy measurements included EASI as well as 5-D Pruritus and ItchyQoL™. Transepidermal water loss (TEWL) and stratum corneum (SC) integrity assay were performed to assess the skin barrier. Skin dysbiosis was measured by S. aureus cultivation, S. aureus abundance (qPCR of thermonuclease gene), and V1-V3 16S rRNA gene sequencing on non-lesional and lesional AD skin. After 12 weeks of bleach baths, 8/15 (53.3%) AD subjects achieved an EASI50 and a significant reduction in itch as measured by 5-D pruritus and Itchy QoL. Eighty-seven percent reported improvements in sleep quality. At study entry, AD subjects had higher non-lesional TEWL values than NA subjects, and only AD subjects experienced a reduction with bleach baths (p = 0.006). Similarly, SC integrity improved as early as 6 weeks after bleach baths in AD subjects. Notably, bleach baths had no significant effect on S. aureus culture-positivity, qPCR absolute abundance, or microbial diversity. The addition of twice-weekly bleach baths improves investigator-assessed AD severity, patient-reported pruritus and sleep as well as physiological measures of skin barrier function in adult AD subjects while having no effect on qualitative and quantitative measures of cutaneous S. aureus. Trial Registration: ClinicalTrials.gov Identifier: NCT01996150, Date of registration: November 27th, 2013. [ABSTRACT FROM AUTHOR]

The Harmonising Outcome Measures for Eczema (HOME) initiative established a core outcome set (COS) for atopic eczema (AE) clinical trials in 2019. This set encompasses four core outcome domains and corresponding measurement instruments: clinical signs (EASI), patient-reported symptoms (POEM and NRS 11 point for worst itch over the last 24 h), quality of life (DLQI/CDLQI/IDQoLI), and long-term control (Recap or ADCT). Following its roadmap, the HOME initiative is now focused on supporting implementation of the COS. To identify barriers and facilitators to implementation of the COS, and to guide the effort to promote COS uptake, a virtual consensus meeting was held over 2 days (September 25–26, 2021) attended by 55 participants (26 healthcare professionals, 16 methodologists, 5 patients, 4 industry representatives, and 4 students). Implementation themes were identified by a pre-meeting survey distributed to HOME members, presentations, and whole-group discussion. Participants were divided into five multi-professional small groups which ranked their top 3 most important themes, followed by whole-group discussion and anonymous consensus voting (consensus criteria: < 30% disagreement). Three most important implementation themes were identified and agreed upon: (1) awareness and stakeholder engagement, (2) universal applicability of the COS, and (3) ensuring minimum administrative burden. Working groups to address these issues are now a priority for the HOME initiative. The results from this meeting will inform the development of a HOME Implementation Roadmap in an effort to support other COS groups planning for effective implementation of their core sets. [ABSTRACT FROM AUTHOR]

Introduction: Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. Methods: A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. Results: A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Conclusion: Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs. Plain Language Summary: The assessment of treatment response is important in determining treatment value in atopic dermatitis (AD). This study aimed to identify which outcome measures and criteria are used to determine treatment response in clinical trials and health technology assessments (HTAs). The psychometric performance of identified outcome measures and criteria was then systematically reviewed to understand which perform best in capturing patient-relevant symptoms and treatment benefits in AD. The review identified and included the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and Peak Pruritus Numerical Rating Scale (PP-NRS) as response measures. Lack of consistency in how response is assessed across clinical trials and HTAs makes it difficult for clinicians and payers to compare the efficacies and cost-effectivenesses of different treatments and to make optimal treatment decisions. The review found that content validity (the extent to which a measure covers those symptoms and treatment benefits which are important to patients) was not assessed for EASI and IGA. EASI and IGA are often used to assess response in clinical trials and HTAs, but they miss key elements of the patient-relevant disease impact and treatment benefit, including itch. Treatments leading to improvements in missed symptoms (e.g. itch) will be undervalued using EASI and IGA, decreasing the chances of regulatory approval and reimbursement. Moreover, response criteria used in clinical trials and HTAs are sometimes adopted in prescriber settings. Here, if response assessment does not capture patient-relevant benefit, patients' access to tailored treatment may be restricted due to the perceived non-response. [ABSTRACT FROM AUTHOR]

Background: For children aged 6–11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. Objectives: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). Methods: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required. Results: Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response. Conclusions: Consistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6–11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit. Trial Registration: ClinicalTrials.gov Identifier NCT02612454. Plain Language Summary: Atopic dermatitis (AD) is a chronic disease that causes recurrent inflamed and rough skin rashes with itching and often soreness. In children with AD, treatment with a medication called dupilumab has shown improvements in their disease and quality of life. But most clinical trials of dupilumab in children have only lasted for 16 weeks. We investigated the effect of dupilumab in children treated for a longer time. The 321 children (aged 6–11 years) who were included in this study had taken part in a clinical trial of dupilumab because they had severe AD. They were treated with either dupilumab or a placebo (a dummy treatment) for 16 weeks. When that trial ended, they were then all treated with dupilumab for up to a year. Their average AD severity continued to get steadily better over a year of extended treatment, with almost all children reaching 50% skin improvement compared with their AD before treatment. Many children reached a point where their skin was clear or almost clear of AD for a period, and following the rules of the study they stopped taking dupilumab. In many of them, their AD slowly returned without treatment. But if they started to take dupilumab again, their AD improved, and some could even achieve skin clearance again. Over the longer term, the safety of dupilumab was similar to what was seen with short-term treatment. This study showed that children with AD aged 6–11 years benefited from receiving dupilumab for a longer period of time. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Bristol Stool Form Scale (BSFS) is a widely used stool scoring method that could indirectly reflect intestinal function. Objectives: To evaluate the associations of AD with BSFS. Methods: This was a population-based cross-sectional study of freshmen in five universities of China. AD diagnosis was performed by dermatologists according to the guideline from the American Academy of Dermatology. BSFS and covariates were collected through an online questionnaire survey. Chronic itch scores were assessed by the numeric rating scales and grouped into quartiles (Q). Mixed logistic regression models were used. Subgroup analysis was conducted by covariates. P value < 0.05 was considered statistically significant. Results: The prevalence of hard stools and loose stools were 8.9% and 7.6%, respectively (20,049 participants). After adjusting covariates, AD was significantly associated with hard stools (OR = 1.38, P < 0.001) and loose stools (OR = 1.24, P = 0.037). In subgroup analysis of hard stool, a stronger effect was observed in intake of milk (> 3 days/week), yogurt (> 3 days/week), pork (< 1 day/week), and higher itch scores (Q4). Conclusion: This study found the relationship between AD and abnormal stool forms, and the association with hard stools might be modified by dietary factor. [ABSTRACT FROM AUTHOR]

Introduction: This real-world, cross-sectional study compared sociodemographic, clinical and treatment characteristics, and patient-reported outcomes (PROs) among racial/ethnic groups in patients with atopic dermatitis (AD) who are candidates for systemic therapy. Methods: This study included adults with dermatologist- or dermatology practitioner-diagnosed AD enrolled in the CorEvitas AD Registry (July 2020–July 2021). All patients initiated systemic therapy within 12 months prior to or at enrollment or had moderate-to-severe AD (vIGA-AD® ≥ 3 and Eczema Area and Severity Index [EASI] ≥ 12) at enrollment. Patients were categorized into five mutually exclusive racial/ethnic groups: non-Hispanic White, Black, Asian, Other/Multiracial, and Hispanic (any race). Patient, clinical, and treatment characteristics were captured at enrollment. Differences in means or proportions of characteristics among racial/ethnic groups were descriptively summarized using effect sizes. Adjusted prevalence ratios and mean differences were estimated (White race/ethnicity group as the reference category) with 95% confidence intervals (CI). Results: Among 1288 patients, 64% (n = 822) were White, 13% (n = 167) Black, 10% (n = 129) Asian, 8% (n = 97) Hispanic, and 6% (n = 73) Other/Multiracial. In adjusted analyses, statistically more severe EASI lichenification was noted among Black compared with White patients at the head and neck (mean difference, 0.21, [95% CI 0.06, 0.36]; p = 0.01), trunk (0.32, [0.17, 0.47]; p < 0.001), upper extremities (0.27, [0.09, 0.44]; p = 0.008), and lower extremities (0.39, [0.21, 0.57]; p < 0.001). Statistically more severe EASI lichenification was observed among Asian vs White patients in certain areas (mean difference, head and neck, 0.22 [0.04, 0.39], p = 0.01; trunk, 0.25 [0.07, 0.43], p < 0.001; lower extremities, 0.22 [0.01, 0.43], p < 0.001) and SCORing for AD lichenification (mean difference: 0.34 [0.15, 0.52]; p < 0.001). Significantly higher mean pruritus over the past 7 days for Black (mean difference: 0.63 [0.01, 1.26] and Hispanic patients (0.60 [0.11, 1.09]; p = 0.03) vs White patients was observed. Among AD clinical features, the prevalence of facial erythema was significantly lower among Black compared with White patients (prevalence ratio = 0.38, [0.22, 0.67]; p = 0.007). Conclusion: Racial/ethnic differences exist in sociodemographic, clinical and treatment characteristics, disease severity, and PROs among real-world AD patients who are candidates for systemic therapy. Recognizing these variations may be of critical importance for dermatologists for the design and delivery of targeted/personalized medicine approaches. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) can require long-term therapy. Few real-world studies have evaluated long-term effectiveness from the patients' perspective. The aim of this study was to evaluate patient-reported outcomes (PROs) during long-term dupilumab treatment. Methods: Adults with moderate-to-severe AD who initiated dupilumab through the US manufacturer patient support program and participated in RELIEVE-AD (a prospective patient survey study with a 12-month follow-up) were recontacted 30–36 months post-initiation regardless of current dupilumab use. The online questionnaire consisted of PROs, including the Atopic Dermatitis Control Tool (ADCT), use of concomitant AD therapies, satisfaction with current therapy, global change in itch relative to before dupilumab initiation, non-itch skin symptoms (skin pain/soreness, hot/burning feeling, and sensitivity to touch), flares, Dermatology Life Quality Index, sleep problems, and the AD-specific Work Productivity and Activity Impairment Questionnaire. Results: Of 698 patients who initiated dupilumab (baseline) and were recontacted, 425 completed the 30–36-month survey. Significant reductions from baseline were reported in concomitant AD therapy use (P < 0.05); 54.4% reported not using other AD medications vs. 12.8% at baseline. At 30–36 months, all results (non-itch skin symptoms, flares, sleep problems, health-related quality of life work/activity impairment, disease control, and treatment satisfaction) were similar to or incrementally better than the 12-month timepoint, with significant improvements vs. baseline (P < 0.001). Global change in itch was reported as "very much better" by 75.3% of respondents. Adequate disease control (score < 7 on ADCT) was reported by 80.7% of respondents, and 86.8% were satisfied with the treatment. Conclusions: In clinical practice settings, patient-reported benefits of dupilumab were maintained in survey respondents during long-term treatment up to 36 months while the use of concomitant AD therapies reduced. Plain Language Summary: Atopic dermatitis (also known as eczema) is a chronic skin disease that can have a profoundly negative effect on patients' quality of life. To control disease symptoms, patients often need long-term treatment. Dupilumab is a treatment that has shown benefits in adults with moderate-to-severe atopic dermatitis (AD) when used in long-term (under 4 years) clinical trials; however, few studies have evaluated patients' experiences of long-term dupilumab treatment outside of a clinical trial setting. This study was conducted to do so: 425 adults with moderate-to-severe AD who received dupilumab through a US manufacturer patient support program filled in an online questionnaire 30–36 months after starting treatment. The questionnaire included items on use of additional AD therapies, AD symptoms, quality of life, disease control, and satisfaction with treatment. Patients' responses showed that, at 30–36 months after starting dupilumab treatment, 54% of patients reported not using any other medications for AD vs. 13% of patients when starting dupilumab treatment. In addition, since starting dupilumab, 75% of patients reported one of the most burdensome AD symptoms, itch, as being "very much better" vs. before starting treatment; 81% reported control of AD symptoms; 85% reported a meaningful improvement in quality of life; and 76% were "extremely" or "very" satisfied with the treatment. In summary, this study showed that long-term dupilumab treatment provides continued improvement in symptoms, treatment satisfaction, disease control, and quality of life in adults with moderate-to-severe AD while reducing the need for other AD treatments. 3iG3PGa9W2P2LdjPJWXwbt Video abstract: How do patients with atopic dermatitis perceive long-term dupilumab treatment in the real world? (MP4 31888 kb) [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease. Cognitive dysfunction was recently demonstrated to be increased in adults and children with AD. However, little is known about the longitudinal course of cognitive impairment in AD and its relationship with pruritus. To investigate the longitudinal course and predictors of cognitive impairment in AD a prospective dermatology practice-based study was performed using questionnaires and evaluation by a dermatologist (n = 210). Patients with ≥ 2 visits were included (mean follow-up time: 318 days). Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8-item Short-Form. At baseline, 20.85% of patients had PROMIS T scores ≤ 45, indicating cognitive impairment (CI). Among patients with CI at baseline, 34.09% had persistent CI, 47.72% had a fluctuating course, and 18.18% had sustained improvement of cognitive function. In repeated-measures regression models, cognitive function scores declined overtime in patients with worse AD severity [SCORing Atopic Dermatitis (SCORAD): p = 0.01, Atopic Dermatitis Severity Index: p = 0.001], increased itch (p = 0.01), skin pain (p = 0.001), and sleep disturbance (p = 0.001). In multivariable logistic regression models, persistent CI was associated with female gender and depressive symptoms [moderate-to-severe Patient Health Questionnaire-9 score (PHQ9)]. Latent class analysis identified two classes of cognitive dysfunction: normal cognition (77.23%), moderate dysfunction (16.21%) and severe impairment (6.55%). Black/African-American race (p = 0.02), moderate-to-severe SCORAD (p = 0.03), dermatology life quality index (p < 0.0001), PHQ9 (p < 0.0001), itch (p = 0.02) and skin pain (p < 0.0001) were more likely to experience moderate dysfunction or severe cognitive impairment. AD is associated with a heterogeneous longitudinal course of cognitive function in adults, with some patients experiencing persistent CI over time. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease. Lebrikizumab, a monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in previous Phase 3 trials: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), and ADhere (NCT04250337). We report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open-label study of lebrikizumab in adolescent patients with moderate-to-severe AD. The primary endpoint was to describe the proportion of patients who discontinued from study treatment because of adverse events (AEs) through the last treatment visit. Methods: Adolescent patients (N = 206) (≥ 12 to < 18 years old, weighing ≥ 40 kg) with moderate-to-severe AD received subcutaneous lebrikizumab 500 mg loading doses at baseline and Week 2, followed by 250 mg every 2 weeks (Q2W) thereafter. Safety was monitored using reported AEs, AEs leading to treatment discontinuation, vital signs, growth assessments, and laboratory testing. Efficacy analyses included Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Body Surface Area (BSA), (Children's) Dermatology Life Quality Index ((C)DLQI), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. Results: 172 patients completed the treatment period. Low frequencies of SAEs (n = 5, 2.4%) and AEs leading to treatment discontinuation (n = 5, 2.4%) were reported. Overall, 134 patients (65%) reported at least one treatment-emergent AE (TEAE), most being mild or moderate in severity. In total, 62.6% achieved IGA (0,1) with ≥ 2-point improvement from baseline and 81.9% achieved EASI-75 by Week 52. The EASI mean percentage improvement from baseline to Week 52 was 86.0%. Mean BSA at baseline was 45.4%, decreasing to 8.4% by Week 52. Improvements in mean change from baseline (CFB) to Week 52 were observed in DLQI (baseline 12.3; CFB − 8.9), CDLQI (baseline 10.1; CFB − 6.5), PROMIS Anxiety (baseline 51.5; CFB − 6.3), and PROMIS Depression (baseline 49.3; CFB − 3.4) scores. Conclusions: Lebrikizumab 250 mg Q2W had a safety profile consistent with previous trials and significantly improved AD symptoms and quality of life, with meaningful responses at Week 16 increasing by Week 52. Trial registration: ClinicalTrials.gov identifier, NCT04250350. Plain Language Summary: Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis Atopic dermatitis is a chronic relapsing inflammatory skin disease that affects up to 15% of adolescents worldwide, with up to 50% suffering from moderate-to-severe disease. Signs and symptoms include dry, cracked skin; redness; itching; and painful lesions, which can negatively affect quality of life and lead to complications, including skin infections. Adolescents also report increased rates of anxiety and stress. Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, the key cytokine in atopic dermatitis, blocking the downstream effects of IL-13 with high potency. Lebrikizumab has been shown previously to improve symptoms of atopic dermatitis, including itch, skin clearance, and quality of life in ADvocate1, ADvocate2 and ADhere. The ADore study aimed to evaluate the safety and efficacy of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. Investigators recruited patients ≥ 12 to < 18 years old, weighing ≥ 40 kg, from Australia, Canada, Poland, and the US who were diagnosed with moderate-to-severe atopic dermatitis. These patients received a loading dose of 500 mg of lebrikizumab at Weeks 0 and 2, followed by 250 mg every 2 weeks for 52 weeks. The safety profile of lebrikizumab was consistent with previously published reports, with mostly mild or moderate adverse events, which did not lead to treatment discontinuation. Lebrikizumab improved skin clearance; 62.6% of patients had clear or almost clear skin by the end of the trial. Lebrikizumab also improved the patients' quality of life. These safety and efficacy results support lebrikizumab's role in treating adolescents with moderate-to-severe atopic dermatitis. D_n9HEaRPQDPZd1tfRjK-9 Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study (MP4 44681 KB) [ABSTRACT FROM AUTHOR]

Chronic eczematous eruptions of aging (CEEA) refers to a heterogenous group of longstanding, pruritic eczematous dermatoses with an unidentified etiology, or those which do not meet strict disease criteria. The literature has not yet established a single ubiquitous disease or term for these eruptions in adults over the age of 65 years. Instead, CEEA is attributed various names, including immunologic eruption of aging, and eruption of immunosenescence. Atopic dermatitis in the elderly, eczema in the elderly, and late- or adult-onset atopic dermatitis or eczema likely also fall under the umbrella of CEEA, given that older patients often do not meet strict criteria for atopic dermatitis. As a reflection of such terminological heterogeneity, CEEA does not have a standardized workup algorithm. This lack of uniformity can obscure the ability to study and understand appropriate treatments for this condition. Yet, as providers become increasingly aware of CEEA and more comfortable in making this diagnosis in older adults, it is necessary that dermatologists understand the safety and efficacy of common CEEA treatments in this population. Here, we discuss special considerations, challenges, and recommendations for treating older adults with CEEA with topical and systemic therapeutics. We provide an overview of therapeutic strategies and potential barriers to treatment and discuss the essential role of shared decision making when caring for this patient population. [ABSTRACT FROM AUTHOR]

Dupilumab is the first human monoclonal antibody that treats atopic dermatitis (AD) by blocking interleukin 4 (IL-4) and interleukin 13 (IL-13), which can suppress the Th2 inflammatory reaction. Effective treatments for pediatric AD patients are limited; therefore, we aimed to assess the efficacy and safety of dupilumab in pediatric AD patients. Fifteen pediatric patients diagnosed with moderate to severe AD and treated with dupilumab were enrolled in this study. SPSS was used to analyze data and obtain the average values of Eczema Area and Severity Index (EASI), SCORing AD (SCORAD), and Children's Dermatology Life Quality Index (CDLQI). GRAPHPAD was used to analyze and plot the statistics. The average EASI values were 19.23 ± 3.03 and 1.69 ± 0.54 at baseline and at following up for 6 months after standardized treatment protocol, respectively. The average SCORAD values were 43.27 ± 4.63 and 6.13 ± 1.41 at baseline and at following up for 6 months after standardized treatment protocol, respectively. The average CDLQI value at baseline was 13.53 ± 2.88 and following up for 6 months after standardized treatment protocol was 1.60 ± 0.63. The most frequent adverse event was conjunctivitis. No serious adverse events occurred during the treatment period. Dupilumab could reduce symptoms and improve pruritus in pediatric AD patients, and the frequent adverse events were reversible. It has a definite therapeutic effect on AD; nevertheless, further studies should be conducted to obtain information on its the long-term efficacy and safety. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD), with its signs and symptoms of pruritus, dryness, and erythema, severely reduces the quality of life (QOL) of affected patients. We investigated the impact of nemolizumab 60 mg on QOL in Japanese patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus, using data derived from patient-reported outcome (PRO) measures. Methods: PROs were the Insomnia Severity Index (ISI), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and Work Productivity and Activity Impairment: Atopic Dermatitis questionnaire (WPAI-AD). Correlations between PRO scores and symptom severity, assessed by the pruritus visual analog scale (VAS) and the Eczema Area and Severity Index (EASI), were explored. Results: The mean percent change (standard error) from baseline in the pruritus VAS and EASI scores at week 16 was, respectively, −45.6% (2.7) and −46.0% (3.2) in the nemolizumab group, and −24.1% (3.7) and −33.2% (4.9) in the placebo group. By week 16, significantly more patients in the nemolizumab group versus the placebo group had an ISI score of 0 for difficulty falling asleep (41.6% versus 13.1%, nominal p < 0.01) or difficulty staying asleep (45.4% versus 10.9%; nominal p < 0.01). Similarly, more nemolizumab- than placebo-treated patients had a DLQI score of 0 for interference with shopping, or home/garden activities (45.2% versus 18.6%, nominal p < 0.01), and 0 days per week of nighttime sleep disturbance (50.8% versus 16.9%, nominal p < 0.01) or bleeding skin (43.4% versus 7.5%, nominal p < 0.01) measured by POEM at week 16. Based on WPAI-AD scores, long-term administration of nemolizumab also improved the ability to conduct work activities. Conclusions: Subcutaneous administration of nemolizumab ameliorated pruritus and skin signs, and thereby produced improvement in patient QOL across multiple PRO measures, including sleep, interpersonal relationships, and the ability to conduct social or work activities. Clinical Trial Registration: JapicCTI-173740 (registered 20 October 2017). [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic, relapsing–remitting illness. In moderate-to-severe instances, recommendations urge patient-centered systemic therapy. Existing standards lack long-term treatment success requirements. A treat-to-target methodology was proposed for systemic therapy patients that requires global improvements to prompt decisions about treatment. Methods: We conducted an observational study between May 2021 and June 2022 in three Ecuadorian patients with severe AD who were treated with dupilumab to assess the clinical evolution and behavior of the subdomains evaluated by clinimetric tools. Results: Patients A and C satisfied disease-domain response criteria to dupilumab at 12 and 24 weeks, but B did not complete the algorithm objectives. Nonetheless, patient A improved AD severity, itching, bleeding, desquamation, sleep, daily activities, mood, emotions, sexual troubles, clothing, and sports subdomains. Patient B experienced reduced symptomatology, AD aggravation, daily activities impact, and work/study impairment. Patient C improved from severe to mild desquamation, itching, exudate, lichenification, and rough/dry skin. Sleep, shame, and study subdomains improved the most. Conclusion: We provide a new operational construct for analyzing current patient-reported outcome measures (PROMs) and clinician-reported outcome measures (CROMs) based on subdomains to widen our understanding of the state of disease activity and make clinical decisions when the treat-to-target strategy is not attained. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is an inflammatory disease causing severe skin itching. Data on patient–physician disconnect on treatment satisfaction in patients with AD in Japan are limited. We investigated patient–physician disconnect on treatment satisfaction in AD and if it influences treatment patterns, clinical characteristics, and patient-reported outcomes (PROs). Methods: Data were drawn from the Adelphi AD Disease Specific Programme (DSP), a real-world, point-in-time survey of physicians and patients with AD conducted in Japan from April to July 2019. Patients and physicians were grouped according to level of treatment satisfaction ("extremely satisfied" to "extremely dissatisfied"); with any level of dissatisfaction recorded as "less than satisfied." Data were collected on treatment patterns, clinical characteristics, and PROs including the Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), EQ-5D-3L questionnaire, and Work Productivity and Activity Impairment (WPAI) questionnaire. Results: Data were provided by 184 patients with AD and 56 physicians; 72.8% of patient–physician pairs reported a fair (kappa coefficient: 0.40) level of agreement on treatment satisfaction, 51.6% of patient–physician pairs were both satisfied, and 21.2% were both less than satisfied. Satisfied physicians prescribed a mean 1.2 fewer treatments than dissatisfied physicians (p < 0.05). Cases where both physician and patient were less than satisfied or where patients were less satisfied than their physicians reported the worst PROs, DLQI (both less than satisfied: mean 10.7 versus patient less satisfied than physician: 10.6 versus overall: 7.9), POEM (19.5 versus 17.3 versus 17.0), EQ-5D-3L (0.82 versus 0.81 versus 0.87) (all, p < 0.05). Work impairment was highest when both patient and physician were less than satisfied (p < 0.05). Physicians cited treatment efficacy and patients cited efficacy and usability as main reasons for dissatisfaction. Conclusion: Overall, 12.0% of patients were less satisfied with their AD treatment than the physician, demonstrating some of the worst PROs, suggesting unmet need that could be improved by better patient–physician communication. [ABSTRACT FROM AUTHOR]

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch. Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS). Results: A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112. Conclusion: UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents. Trial Registration: ClinicalTrials.gov identifier, NCT03661138. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral Janus kinase 1 inhibitor, provided significant itch relief by week 2 in patients with moderate-to-severe atopic dermatitis (AD) in the phase III JADE COMPARE trial. Objectives: This post-hoc analysis of JADE COMPARE aimed to further characterize itch response and determined whether early itch relief could predict subsequent improvements in AD severity. Methods: JADE COMPARE was a randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (aged ≥ 18 years) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200 mg or 100 mg once daily, subcutaneous dupilumab 300 mg every other week (after a 600-mg loading dose), or placebo, plus medicated topical therapy for 16 weeks. Assessments were ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) from days 2 to 15, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA) response, and Dermatology Life Quality Index (DLQI) scores at week 12. Association between week 2 PP-NRS4 and efficacy at week 12 was evaluated by chi-squared tests. The predictive value of early response for later efficacy was assessed by area under the receiver operating characteristic curve. Results: As early as day 4 after treatment, a significantly greater proportion of patients achieved PP-NRS4 response with abrocitinib 200 mg (18.6%) versus dupilumab (5.6%; p < 0.001) and placebo (6.0%; p < 0.003). A similar trend was observed with abrocitinib at the 100-mg dose, with significantly greater PP-NRS4 response rates versus placebo as early as day 9. With both doses of abrocitinib, week 12 IGA 0/1, EASI-75, EASI-90, and DLQI 0/1 response rates were greater in week 2 PP-NRS4 responders than nonresponders; no differences were observed between week 2 PP-NRS4 responders and nonresponders in the dupilumab and placebo groups. Early improvement in PP-NRS at week 2 was associated with skin clearance at week 12 in abrocitinib-treated patients. Conclusions: Abrocitinib resulted in rapid relief from itch in patients with moderate-to-severe AD, with significant improvement in itch as early as day 4 after treatment with abrocitinib 200 mg compared with dupilumab and placebo. Abrocitinib-induced itch relief by week 2 was associated with subsequent improvements at week 12. [Video abstract available.] Trial registration: ClinicalTrials.gov identifier: NCT03720470. 2fQ_82bhGurT9XTD9WAh-8 Early itch response with abrocitinib is associated with later efficacy outcomes in patients withmoderate-to-severe atopic dermatitis: subgroup analysis of the randomized phase III JADE COMPARE trial (MP4 335,375kb) Plain Language Summary: An investigation into whether quick relief from itch with abrocitinib, a new medicine for atopic dermatitis, leads to later improvements in skin rash Atopic dermatitis (AD), also called atopic eczema, is a skin disease that affects people throughout their lives. About 10% of adults worldwide have AD. Itch is the most bothersome symptom reported by people with AD and scratching this itch can damage the skin, resulting in painful sores. It is unknown if relief from itch can influence other symptoms of AD. We analyzed data from the JADE COMPARE study, which included 837 people who received treatment with abrocitinib, dupilumab or placebo. We studied how fast itch relief occurred after people received these treatments. We also wanted to study if rapid itch relief was associated with improvement in other signs of AD later on with continued treatment. We found that as early as 4 days after treatment, abrocitinib 200 mg provided significant relief from itch compared with dupilumab or placebo. People who had rapid itch relief within 2 weeks of treatment with abrocitinib were more likely to have clear or almost clear skin and improved quality of life after 12 weeks of continued treatment with abrocitinib. Rapid itch relief did not appear to increase the likelihood of clear skin at week 12 in people who received dupilumab. Larger studies are needed to confirm this result. This study provides important evidence for physicians as they analyze itch relief and determine treatment options for people with AD. [ABSTRACT FROM AUTHOR]

Introduction: Three patient-reported outcome (PRO) questionnaires—Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)—were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation. Methods: Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate–severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups. Results: The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1–2 with minimal, 3 with mild, 4–7 with moderate, and 8–10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3–6 with moderate, and 7–10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0–1 was associated with absent, 2–11 with minimal, 12–22 with mild, 23–47 with moderate, and 48–70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1–3 with minimal, 4–6 with mild, 7–20 with moderate, and 21–30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1–2 with minimal, 3–7 with mild, 8–25 with moderate, and 26–40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1–2 with minimal, 3–8 with mild, 9–22 with moderate, and 23–30 with severe. Conclusions: These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice. Trial Registration Number: NCT03568318. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a relatively common inflammatory skin disease marked by eczematous lesions and pruritus often leading to significant morbidity and quality of life impairment for those affected. Recent studies have shown that patients with skin of color (SOC) carry a larger disease burden than patients of European descent. In the USA, these disparities are partly due to structural, environmental, and interpersonal racism. From a global perspective, there is a paucity of research on the burden of atopic dermatitis and other inflammatory skin diseases experienced by the record numbers of refugees, migrants, and asylum seekers around the world. Although it is still unclear whether the true prevalence of AD in displaced communities is higher compared with the general population, those who are displaced suffer from unique risk factors that render them especially vulnerable. In this review, we outline a number of factors contributing to AD susceptibility and/or aggravation in displaced communities. These include poor living conditions, climate change events, psychological stress, and lack of access to medical care and health-related behaviors. [ABSTRACT FROM AUTHOR]

Introduction: Adults with atopic dermatitis (AD) commonly report adult-onset disease. AD is associated with different genetics, lesion morphology and distribution, and symptoms by age of onset. Yet little is known about possible differences in treatment efficacy between adults with adult-onset or childhood-onset AD. Methods: We evaluated the efficacy of dupilumab by age of AD onset in adults with moderate-to-severe AD, using pooled data from the LIBERTY AD SOLO 1 and 2 studies (NCT02277743, NCT02277769). Results were stratified based on self-reported age of AD onset, divided into four age subgroups: 0–4, 5–9, 10–19, and over 20 years. Results: This analysis included 460 patients treated with placebo and 457 treated with dupilumab 300 mg every 2 weeks (q2w), with a mean patient age of 38 years. Most patients (53.2%) reported AD onset at 0–4 years, with 14% at 5–9 years, 13.4% at 10–19 years, and 18.5% at 20 years or older. Dupilumab significantly improved AD signs and symptoms over 16 weeks compared with placebo, regardless of age of onset. Dupilumab treatment resulted in a significantly greater proportion of patients achieving Eczema Area and Severity Index (EASI)-50, EASI-75, and EASI-90 (50%, 75%, and 90% improvement from baseline EASI, respectively), and clear or almost clear skin (Investigator's Global Assessment score 0 or 1) across all age-of-onset subgroups compared with placebo. In addition, EASI improvements were significant across all anatomical regions in all subgroups. Weekly average peak pruritus Numerical Rating Scale and Dermatology Life Quality Index also improved consistently and significantly with dupilumab versus placebo, regardless of age of onset. Conclusion: Despite possible differences in presentation and progression of AD linked to age of onset, dupilumab showed similar significant and sustained improvements in AD signs, symptoms, and quality of life in adults compared with placebo, over 16 weeks of treatment. Trial Registration: LIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769. Infographic available for this article. Plain Language Summary: Atopic dermatitis (AD, also known as eczema) is a skin disease with itchy, red rashes. AD often develops during childhood, but can also start in adulthood. Depending on the age it starts, AD may have different triggers and appearance, and might require different treatment. A medicine called dupilumab, which targets two proteins that cause inflammation, has provided benefit in children and adults with AD. We wanted to know if the age at which AD starts (during infancy, childhood, adolescence, or adulthood) impacts the improvement of dupilumab in adult patients. We looked at 917 adults, who participated in two studies taking dupilumab or a dummy treatment (placebo) every 2 weeks for 4 months. We compared four groups of patients with different ages of AD onset. The results showed that dupilumab compared with the placebo reduced skin lesions, relieved itch, and improved quality of life in a similar way in all adults, regardless of whether their disease started earlier or later in life. In the four groups, dupilumab reduced skin lesions across all areas of the body. Together with the previously reported safety data, our results support the use of dupilumab in adults with moderate-to-severe AD, irrespective of age of disease onset. Infographic: [ABSTRACT FROM AUTHOR]

Introduction: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6–11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. Methods: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6–11 years with severe AD. These included test–retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. Results: The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. Conclusions: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6–11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3–4-point change in the Worst Itch Scale score. Trial Registration: NCT03345914. AJhHpBhQDRLsLFeB17Gfds Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings? [ABSTRACT FROM AUTHOR]

Background: There is a clear link between skin disease and psychological factors and this relationship works both ways: skin diseases can cause psychological distress and psychological issues can worsen skin disease. There are a number of therapies that approach this problem from the psychological side and may be useful, especially as adjunctive therapies in select patients. Objective: The aim of this review was to determine the efficacy of various psychological therapies and mind–body techniques in the management of common dermatologic diseases in individuals of all ages. Methods: A systematic review of PubMed, Elsevier, and Wiley was performed for studies investigating psychological and mind–body interventions in the management of various skin diseases. Both physical and non-physical treatment outcomes were considered. Studies were evaluated for both risk of bias and overall quality of evidence. Results: A total of 40 articles studying unique sets of dermatological patients receiving psychological therapies or mind–body interventions were identified. Of the 40 included articles encompassing 3112 patients, 18 investigated these interventions in psoriasis management while 15 focused on atopic dermatitis. The remaining studies investigated vitiligo (2), pruritus (2), acne vulgaris (2), and acne excoriée (1). Conclusions: Based on the analysis of included studies and an assessment of their quality of evidence, the most promising interventions are cognitive behavioral therapy, mindfulness-based interventions, and habit reversal therapy. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that is triggered by intense pruritus, impaired skin barrier function, and immune responses to allergenic substances. Break-through therapies for AD include molecular-targeted drugs and the effective management of severe symptoms of AD. However, patients with clinical improvements may continue scratching owing to the influence of psychological stress, which might lead to quick relapses of stressors and subsequent intensive scratching. New drugs may be ineffective because of such scratching behavior caused by stressors. Therefore, it may be useful to consider adjunctive treatment options that focus on external stressors as triggers of deterioration of AD. We hypothesized that improvement of psychological stress by relieving cervical muscle tension would reduce pruritus and atopic symptoms. Methods: Overall, 21 patients with moderate-to-severe AD were treated to relieve cervical muscular tension using Spineliner SA201, which assists in osteopathic manipulative treatment. We assessed the subjective and objective symptoms of AD, cervical muscle tension, which was evaluated using cervical range of motion (ROM), and psychological burden. Only moisturizers were applied topically during the study period, and no topical corticosteroid therapy was used. Results: Twenty patients who completed the treatment demonstrated improvement in the symptoms of AD: changes on the visual analog scale (VAS) for pruritus were −44.2%, Eczema Area and Severity Index (EASI) was −67.9%, thymus and activation-regulated chemokine (TARC) was −56.2%, Hospital Anxiety and Depression Scale (HADS) was −27.2%, sleep disturbance was −49.7%, and Dermatology Life Quality Index (DLQI) was −46.7%. Additionally, the cervical muscle tension improved significantly: changes in cervical ROM were 14.7%. Conclusions: Release of cervical muscle tension may improve psychological stress and have an effect on moderate-to-severe AD. Plain Language Summary: Atopic dermatitis is a chronic relapsing inflammatory skin disease triggered by intense pruritus, impaired skin barrier function, and immune responses. Standard dermatological therapies for patients with atopic dermatitis include topical glucocorticoid treatments. In some cases, scratching and inflammation could not be adequately controlled, a relapse could not be prevented after remission, and their efficacy is limited. Break-through therapies for atopic dermatitis include new molecular biological drugs, which have demonstrated significantly improved and effective management of severe atopic symptoms. However, patients with clinical improvements may continue scratching owing to psychological stress, which might lead to quick relapses of stressors and subsequent intensive scratching. New drugs may be ineffective owing to such scratching behavior caused by stressors. Therefore, it may be useful to consider adjunctive treatment options focusing on external stressors as triggers for worsening atopic dermatitis. We hypothesized that improvement of psychological stress by relieving cervical muscle tension would reduce pruritus and atopic symptoms. Overall, 21 patients with moderate-to-severe atopic dermatitis were treated to relieve cervical muscular tension using Spineliner SA201, which assists in osteopathic manipulative treatment. We assessed the subjective and objective atopic symptoms, cervical muscle tension, and psychological burden. Only moisturizers were applied topically during the study period, and no topical corticosteroid therapy was used. Twenty patients completed the treatment, atopic symptoms improved significantly, cervical muscular tension improved, and the psychological burden decreased with the treatment. Release of cervical muscle tension may improve psychological stress and affect moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic pruritic skin disease that can have a profound negative impact on patients' quality of life, especially in cases of inadequate disease control. Dupilumab, a dual inhibitor of IL-4 and IL-13 signaling, is approved in the United States for the treatment of moderate-to-severe AD in adults (≥ 18 years old) and in children (≥ 6 years old). In this review, we present results from phase 3 trials evaluating dupilumab's efficacy and safety in adults, adolescents, and children. These trials demonstrate that dupilumab provides rapid improvements (in as little as 1 week) and sustained efficacy (up to 4 years) when used as a treatment for moderate-to-severe AD. Dupilumab not only improves skin signs and symptoms, but also provides multiple health benefits beyond the skin, including improvements in quality of life, itch, sleep disturbances, and pain/discomfort. Dupilumab is generally well tolerated, has a favorable safety profile in adults, adolescents, and children, has no serious drug–drug interactions, does not require routine laboratory testing, and is not an immunosuppressant. Taken together, phase 3 trials demonstrate that dupilumab provides rapid and sustained efficacy and is generally well tolerated for the treatment of moderate-to-severe AD across age groups. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex and multifactorial skin disease characterized by skin inflammation and intense pruritus. There are many commercially available treatments such as topical corticosteroids and immunosuppressants to treat of AD, but their effectiveness is limited, and frequent use of these treatments can cause serious side effects. Therefore, the development of new therapeutic agents is necessary for the treatment of AD. Hence, an alternative agent that was derived from natural products that are effective and safe for AD treatment was investigated using experimental models. The biological activity of euscaphic acid has anti-inflammatory, anticoagulant, and antioxidant effects. Despite the various biomedical properties of euscaphic acid, its therapeutic effects on AD have not been well studied. In this study, we investigated the effects of euscaphic acid on skin inflammation and pruritus in AD mouse model. The effects of euscaphic acid were investigated in activated human epidermal keratinocytes and leukemia T lymphoblast cell lines, and Dermatophagoides farina extract and 2,4-dinitrochlorobenzene-induced AD mouse model. Euscaphic acid ameliorated AD properties, such as the expression of inflammatory cytokines and activation of transcription factors. In addition, euscaphic acid reduced critical factors for pruritus such as immunoglobulin E hyperproduction, mast cell invasion, and interleukin-33 expression. Taken together, euscaphic acid could be a potent therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

Chronic pruritus carries a significant burden of disease and is associated with a negative impact on quality of life. African Americans are disproportionately burdened by chronic pruritic disorders, including but not limited to atopic dermatitis, prurigo nodularis, inflammatory scalp dermatoses, pathologic scarring, and HIV-related dermatoses. Racial differences in skin structure and function may contribute to the pathogenesis of itch in African Americans. Itch perception and response to treatment in African Americans remain understudied and not well understood. As such, there is a large unmet need with regard to the knowledge and management of pruritus in African Americans. This review highlights notable differences in the epidemiology, pathophysiology, genetic predisposition, clinical presentation, and response to treatment for select pruritic skin conditions. By addressing itch as an unmet need in African Americans, we hope to improve patient outcomes and lessen disparities in dermatologic care. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic inflammatory skin condition which impacts psychological wellbeing and social relationships. There have been studies of AD's impact on quality of life (QoL) in Western countries, but these findings cannot be directly extrapolated to Asian populations with genetic, environmental and cultural differences. Therefore, we aimed to systematically review the literature pertaining to QoL impairment in AD in East and Southeast Asia to characterize the impact of AD on patients and their families, and to identify the factors affecting the degree of QoL impairment. A search of English language papers was conducted on MEDLINE, EMBASE, PSYCInfo, Global Health and Web of Science. Observational studies measuring QoL using single or multi-item instruments in people with self-reported or physician diagnosed atopic dermatitis were included. 27 studies from 29 articles were included and synthesized. There is data documenting QoL impairment in AD sufferers and their families, across a wide range of Asian countries, healthcare settings and ages. Aspects of QoL impacted to a greater extent included symptoms of itch, feelings of embarrassment, and sleep disturbance. Severity of disease affects the degree of impairment of QoL, but there is no apparent link between QoL impairment and patient demographic factors, or other medical factors such as age at diagnosis or duration of illness. Our findings also highlighted the need for clinicians to actively explore the impact of patient's symptoms, especially in an Asian context where healthcare communications are traditionally doctor-centric. [ABSTRACT FROM AUTHOR]

Introduction: While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch. Methods: From Modernizing Medicine's Electronic Medical Assistant dermatology-specific electronic medical records, adults (≥ 18 years) were identified with a diagnosis of AD and ≥ 1 dupilumab prescription (index event) between 1 April 2017 and 31 January 2019. Three cohorts were identified based on 3-month pre-index (1) Investigator Global Assessment (IGA) score ≥ 3, (2) an itch severity numerical rating scale (NRS) score ≥ 3, and (3) body surface area (BSA) affected ≥ 10%. Changes from pre-index on the outcome within each cohort were evaluated at 4 months post-index. Patients were also stratified for evaluation of outcomes by baseline demographic (sex, age) and prior AD treatments (topical therapy only or no treatment, any systemic therapy). Results: More than 70% of the 435 AD patients with baseline IGA score ≥ 3 improved to an IGA score of ≤ 2 at month 4 post-dupilumab initiation, including 42.8% who achieved IGA 0/1 (clear/minimal). Among 112 patients with a pre-index itch severity NRS ≥ 3, scores were reduced from mean (SD) 7.0 (2.4) pre-index to 2.8 (2.8) at month 4 (p < 0.0001); 70.5% of patients had a reduction ≥ 3 points. In the BSA cohort (n = 387), affected BSA was significantly reduced from a pre-index mean (SD) of 39.3% (26.1%) to 16.3% (21.2%) at month 4 (p < 0.0001). Significant improvements in IGA, itch NRS, and BSA were observed regardless of demographic (age and sex) or clinical characteristics such as treatment history (all p < 0.0001 compared with pre-index). Conclusions: Consistent with outcomes observed in clinical trials, patients treated with dupilumab in real-world clinical settings achieved clinically meaningful improvements in severity and extent of AD and severity of itch comparable to those reported in clinical trials at a similar time point. [ABSTRACT FROM AUTHOR]

Introduction: As research continues, new drugs will no doubt be added to the current pool of treatments for moderate-to-severe atopic dermatitis (AD). This raises the need for studies to determine prescriber preferences for different pharmacological options and the factors that influence their choice of treatment. Here we aim to explore physician preferences in the systemic treatment of moderate-to-severe AD, identify the sociodemographic characteristics that can influence physician preferences, and evaluate their satisfaction with current AD therapies. Methods: A discrete-choice experiment (DCE) survey was administered to physicians treating patients with AD in Spain. Results were analyzed using a conditional logit model to estimate the relative importance of each attribute and the maximum risk accepted to achieve therapeutic benefit. Results: A total of 28 respondents completed the DCE survey (67.9% female, mean age 45.9 years). Participants identified objective clinical efficacy and risk of severe adverse events (AEs) as the most important attributes, followed by improvement in sleep and pruritus and faster onset of action from the start of the treatment. Respondents gave less importance to mode of administration and therapeutic benefit in other atopic conditions. Respondents were willing to accept an increased risk of severe AEs and mild-to-moderate AEs leading to treatment discontinuation due to intolerance in order to obtain improvements in efficacy, sleep, and pruritus, and long-term clinical benefit. Conclusion: Our findings can help prescribers choose the most appropriate systemic AD therapy. [ABSTRACT FROM AUTHOR]

Tralokinumab (tralokinumab-ldrm) [Adbry™ (USA); Adtralza® (EU)], a human IgG4 monoclonal antibody that binds specifically to interleukin (IL)-13, is an effective and generally well tolerated treatment option for adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy. In pivotal phase III trials, subcutaneous tralokinumab improved the clinical signs and symptoms of atopic dermatitis as well as quality of life (QOL). In ECZTRA 1 and 2, tralokinumab monotherapy was superior to placebo in the first 16 weeks of treatment, with improvements in pruritus and sleep scores seen as early as week 1. Many patients who met the criteria for clinical response at week 16 maintained this response at week 52. Tralokinumab was also more effective than placebo when used in combination with 'as needed' topical corticosteroids (TCS) in ECZTRA 3 and 7; most tralokinumab recipients used no or very little amounts of TCS. In an open-label extension trial, tralokinumab provided consistent symptom control over the longer term (up to 2 years). The majority of adverse events with tralokinumab, including injection-site reactions and conjunctivitis, were of mild to moderate severity. The tolerability profile of tralokinumab longer term was consistent with that in the phase III trials. Plain Language Summary: Atopic dermatitis is an ongoing inflammatory skin condition that causes dryness, itching and redness. Standard first-line treatments include moisturizers and medical ointments that are applied directly to the skin. However, topical treatments often fail to adequately control symptoms in patients with moderate to severe disease. More recently, biological therapies have been developed that target the different inflammatory proteins involved in atopic dermatitis. Tralokinumab [Adbry™ (USA); Adtralza® (EU)] is a human monoclonal antibody that targets IL-13, a key protein involved in driving the signs and symptoms of atopic dermatitis. When given alone or together with topical corticosteroids, subcutaneous tralokinumab improves the signs and symptoms of atopic dermatitis in adults with moderate to severe disease and provides consistent long-term disease control. Patients treated with tralokinumab also report improvements in health-related quality of life. Adverse events seen with tralokinumab are generally mild or moderate in severity. Thus, subcutaneous tralokinumab offers a new effective and generally well-tolerated treatment option for adults with moderate to severe atopic dermatitis who require systemic therapy. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric atopic dermatitis (AD) leads to a considerable reduction in quality of life for patients and their families. Therapeutic options for pediatric patients with moderate-to-severe disease are limited and treatment is challenging. As little is understood about physician perceptions of pediatric AD in countries with emerging healthcare, we conducted a questionnaire-based study to identify treatment patterns and gaps. Methods: Physicians treating children (aged 6–11 years) and adolescents (aged 12–17 years) with AD in 11 emerging economy countries were interviewed regarding their beliefs and behaviors relating to the disease. Physicians gave an initial assessment of patient disease severity and control, which was then compared with patient records and pre-specified criteria to assess concordance and discordance between physician perception and recorded patient presentation. Results: A total of 574 physicians completed the study, with an assessment of 1719 patients. Only 51% of patients whose disease criteria matched 'severe disease' to pre-specified criteria and SCORing Atopic Dermatitis scores (SCORAD) were also initially identified by physicians as having severe disease. Patients with moderate-to-severe disease experienced flares for an average of 263 days in the preceding year. Ninety and 74% of patients experienced chronic flares and unpredictable flares, respectively. Control of flares could only be achieved within 7 days in 14% (n = 153) of patients. Most physicians listed elimination of skin symptoms as their primary treatment goal, and for moderate and severe cases, 59% and 33% of physicians reported that they were able to achieve this respectively. Nearly 24% and 40% of physicians were slightly dissatisfied with the treatment options for moderate disease and severe disease and severe disease, respectively. Conclusions: AD severity of children (aged 6–11 years) and adolescents (aged 12–17 years) appears to be underestimated by physicians in emerging economy countries. Practical, easy-to-use, and validated objective measures for assessment of disease severity and control, as well as effective use of novel therapies, are essential to ensure that patients are appropriately managed. Plain Language Summary: Atopic dermatitis (AD) is a common childhood disease that occurs in up to 30% of individuals under 18 years of age. Although most forms are mild, more severe disease forms of AD including symptoms such as pruritus, xerosis, lichenification, and excoriation of the skin can cause significant problems, such as lack of sleep, lack of productivity, poor self-image, and mental health disorders among patients. It also places a burden on patients' families, which affects home, school, and work life. In children with moderate-to-severe disease, treatment options are limited especially since doctors may not be keen to prescribe high-dose treatments to children such as potent and super-potent topical corticoid steroids and progress to systemic therapies. Relatively little is understood about how doctors determine whether the disease is mild, moderate, or severe and what they consider to be the best treatment options for patients. Therefore, we conducted a series of interviews with doctors in 11 countries with emerging healthcare to better understand their beliefs and behaviors about treating childhood AD. Our results indicated that doctors tended to underestimate the severity of a patient's disease. Additionally, 59% of doctors felt that they were able to successfully eliminate itching and skin syndrome frequently (that is, in 70% or more of their patients) in patients with moderate disease and 33% of doctors for their patients with severe disease. These results suggest that there are many unmet needs in the treatment of children and adolescents with AD in emerging economies, whose treatment could be further optimized. Improving how doctors measure the severity of a patient's disease should help them select the most appropriate and effective treatments for their patients. [ABSTRACT FROM AUTHOR]

Introduction: Emollients reduce the severity of dermatitis-associated symptoms. Antioxidant supplementation may be helpful to control inflammatory processes and consequential skin damage. The clinical performance and safety of an emollient medical device for topical treatment enriched with antioxidant ingredients in adults with mild-to-moderate dermatitis is presented in this manuscript. Methods: We performed a monocenter, open‐label, uncontrolled clinical trial. Participants applied the product twice a day for 28 days. No other medication or moisturizer was allowed. Changes in dermatitis severity were assessed at days 14 and 28 by study investigators. Subjects self-assessed pruritus, Dermatology Life Quality Index, and product satisfaction. At the end of the study, a global evaluation of the product was done both by patient-reported outcomes and investigators' evaluations. Results: Forty subjects were enrolled in the study (mean age 35 years). Treatment success was achieved in 87.5% of subjects (p < 0.0001) after 28 days. Mean Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) scores decreased at days 14 and 28 (p < 0.0001). Subjects reported a reduction in pruritus severity and improvement of quality of life (p < 0.0001), along with satisfaction with the product. At the end of the study, skin condition improved in more than 90% of subjects. No safety issues were identified. Conclusion: The medical device studied for topical use in this clinical trial is considered safe and reduces pruritus in adults with atopic and contact dermatitis. [ABSTRACT FROM AUTHOR]

Itch is a complex symptom that is both common and burdensome in atopic dermatitis (AD). Yet, little is known about the longitudinal course of itch in AD. A prospective, dermatology practice-based study was performed of adults with AD (n = 463). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. Itch was assessed using Numeric Rating Scale (NRS) average and worst-itch scores, and frequency of itch in the past week. Repeated-measures regression models were constructed to examine itch over time. Overall, 31.5% and 22.5% had moderate (4–6) or severe (7–10) NRS average-itch scores; 27.4% and 36.4% had moderate (4–6) or severe (7–10) NRS worst-itch scores; 12.7% and 62.0% had itch from eczema 3–4 and ≥ 5 days in the past week; 27.4% and 45.1% reported sometimes and often/almost always having itch, respectively. Among patients with baseline moderate (4–6) or severe (7–10) NRS average-itch scores, 21.2% and 16.3% continued to have moderate or severe scores at ≥ 1 follow-up visits. In repeated-measures regression models, persistent NRS average-itch scores were associated with baseline NRS average-itch [adjusted β (95% CI): 0.75 (0.68, 0.82)] and food allergy [− 0.45 (− 0.84, − 0.07)]. Persistent NRS worst-itch was associated with baseline worst-itch NRS [0.73 (0.66, 0.80)] and Medicaid insurance [1.06 (0.17, 1.94)]. AD patients had a heterogeneous longitudinal course with fluctuating and complex overlapping patterns of average- and worst-itch intensity, and frequency. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory skin diseases are a significant burden on affected patients. Inflammation is caused by various stress factors to the epidermis resulting in, e.g., dryness, redness, and pruritus. Emollients are used in basic therapy to restore the natural skin barrier and relieve symptoms. A systematic review was performed to evaluate the efficacy and safety of ectoine-containing topical formulations in inflammatory skin diseases characterized by an impaired skin barrier. Methods: A systematic review was carried out in PubMed, the Cochrane Library, and Microsoft Academic up to October 2021. Inclusion criteria were ectoine-containing topical formulations (creams, emollients) used for (adjuvant) therapy of inflammatory skin diseases. Clinical studies of any design published in any language were included. Results: A total of 230 references were screened for eligibility, of which six were selected for inclusion in the review (five studies on atopic dermatitis and one study on prevention and management of retinoid dermatitis). The application of topical formulations containing 5.5–7.0% ectoine positively influenced skin dryness and, consequently, pruritus and dermatitis-specific scores in patients with atopic dermatitis. Especially in infants and children, who belong to the most frequently affected group, the formulations were well-tolerated when applied for up to 4 weeks. In studies where ectoine was used as an adjuvant therapy, application was associated with a decreased need for pharmacological therapy and also improved the effectiveness of, e.g., topical corticosteroids. In patients undergoing isotretinoin therapy, ectoine was as effective as dexpanthenol in reducing retinoid dermatitis or improving symptoms. Conclusion: Ectoine is an effective natural substance with an excellent tolerability and safety profile, representing a beneficial alternative as basic therapy or to increase the efficacy of the pharmacological treatment regimen for patients with inflammatory skin diseases, including infants and children. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5. Methods: Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder. Results: At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10–50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints. Conclusion: Baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy. Clinical Trial Registration: NCT03435081. Plain Language Summary: Baricitinib is a medication that helps a dysregulated immune system readjust. This leads to improvements in the inflammatory disease atopic dermatitis (AD). Baricitinib is approved for adults with moderate-to-severe AD in over 40 countries. In the ongoing study BREEZE-AD5, baricitinib 2 mg improved moderate-to-severe AD in patients who previously did not respond to or could not tolerate topical corticosteroids. Understanding which patients are likely to benefit most from a medication can improve patient experience with treatment. It can also ensure that only patients who are likely to benefit from a medication are exposed to it. This analysis aimed to identify patients who are most likely to benefit from baricitinib 2 mg in BREEZE-AD5, using an approach based on baseline body surface area (BSA) affected and early clinical improvement. We showed that patients with moderate-to-severe AD affecting between 10% and 50% of their BSA account for the majority of patients who respond to baricitinib 2 mg after 16 weeks of treatment. Clinical assessment of skin inflammation or itch in patients after 4–8 weeks of initiation of baricitinib 2-mg treatment further improved the ability to identify patients who are most likely to benefit from long-term therapy. This proposed clinical tailoring approach of baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may allow for the treatment of patients who are most likely to respond to therapy, and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg. [ABSTRACT FROM AUTHOR]

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD), a predominantly type 2 inflammatory skin disease, affects approximately 2–5% of adults, with a high burden of disease. In moderate-to-severe AD, lesions can be extensive and pruritus intense with patients experiencing skin pain, sleep and mental health disturbances, and diminished quality of life (QoL). Methods: The objective of this study was to evaluate the efficacy of dupilumab for the treatment of AD from the patients' perspective using patient-reported outcome data from four clinical trials (CHRONOS, SOLO 1&2, and CAFÉ) in patients (N = 1553) receiving either the approved 300 mg q2w dupilumab with/without topical corticosteroids (TCS) dose or control (placebo or placebo + TCS). Patient Global Assessment of Disease Status (PGADS) was used to measure patients' well-being and Patient Global Assessment of Treatment Effect (PGATE) was used to measure treatment efficacy. Patients were asked "Considering all the ways in which your eczema affects you, indicate how well you are doing" to assess their perception of well-being and "How would you rate the way your eczema responded to the study medication?" to assess their perception of treatment effect. Possible responses for both metrics included poor, fair, good, very good, and excellent. Results: In all four studies, a significantly higher proportion of dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" disease status from week 2 through study end versus control (CHRONOS, 52 weeks: 69.8% vs. 25.1%; SOLO 1&2, 16 weeks: 59.5% vs. 24.6%; CAFÉ, 16 weeks: 84.1% vs. 45.4%; all P < 0.0001), and significantly more dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" treatment efficacy versus control (CHRONOS: 72.6% vs. 24.8%; SOLO 1&2: 65.0% vs. 21.1%; CAFÉ, 16 weeks: 85.0% vs. 36.1%; all P < 0.0001). Conclusion: Adult patients with AD perceived that dupilumab with/without concomitant TCS was highly efficacious and improved overall disease status and well-being as early as week 2 and throughout treatment periods up to 1 year. 54JKTqmo75hYgJCC19i13y Video Abstract (MP4 90521 kb) [ABSTRACT FROM AUTHOR]

Normally, an obvious antagonism exists between pain and itch. In normal conditions, painful stimuli suppress itch sensation, whereas pain killers often generate itch. Although pain and itch are mediated by separate pathways under normal conditions, most chemicals are not highly specific to one sensation in chronic pathologic conditions. Notably, in patients with neuropathic pain, histamine primarily induces pain rather than itch, while in patients with atopic dermatitis, bradykinin triggers itch rather than pain. Accordingly, repetitive scratching even enhances itch sensation in chronic itch conditions. Physicians often prescribe pain relievers to patients with chronic itch, suggesting common mechanisms underlying chronic pain and itch, especially peripheral and central sensitization. Rather than separating itch and pain, studies should investigate chronic itch and pain including neuropathic and inflammatory conditions. Here, we reviewed chronic sensitization leading to chronic pain and itch at both peripheral and central levels. Studies investigating the connection between pain and itch facilitate the development of new therapeutics against both chronic dysesthesias based on the underlying pathophysiology. [ABSTRACT FROM AUTHOR]