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Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease with a high disease burden, is one of the most common dermatological conditions in Japan. Herein, we report the disease profiles and current AD treatment during 2-year management of Japanese adults with moderate-to-severe AD. ADDRESS-J was a prospective, longitudinal, observational study that evaluated real-world effectiveness and safety of current AD treatments of adult patients with moderate-to-severe AD (Investigator's Global Assessment score 3 or 4) in Japan. The maximum follow-up period was 2 years. Among 300 patients enrolled, 288 had ≥1 post-baseline evaluation and were analyzed (mean age, 35.5 years; 60.1% male). Almost all patients (99.7%) received topical therapy; the most commonly used therapy was topical corticosteroids of the second-highest potency (86.5%) (e.g., 0.1% mometasone furoate) followed by medium-potency topical corticosteroids (50.3%) (e.g., 0.05% clobetasol butyrate). At month 12 of the study, 10.4% of patients had Investigator's Global Assessment 0/1, similarly at month 24 (10.8%). A total of 132 patients (45.8%) had ≥1 AD flare-up during the observation period, with the majority of first flares occurring within the first year of the study. Various physician- and patient-reported outcomes improved considerably during the first 3 months of the study, with only minor changes after this time. In this cohort, 16.7% of patients had skin infections requiring treatment; 7.3% had adverse events (AE) potentially related to treatment; 1.7% had serious AE; and 1.0% had treatment discontinuations due to AE. Limitations include missing data at later timepoints and the inclusion criteria limiting generalizability. In summary, this analysis of the ADDRESS-J study showed that some patients with moderate or severe AD respond to conventional therapies, while others do not. For those with inadequately controlled moderate-to-severe AD, the newly emerged systemic agents, such as biologics, may provide a potential strategy for long-term disease management.

Atopic dermatitis (AD, also called atopic eczema) is a long-term skin disease that causes intensely itchy, red skin. Healthcare providers can prescribe medicated creams and ointments to reduce the signs and symptoms of AD. However, these treatments are not always enough to provide relief. A new medicine called abrocitinib, which is taken every day as a tablet, reduces part of the body’s immune response that happens in AD. The clinical study described in this plain language summary, called JADE COMPARE, investigated how well and how safely 16 weeks of treatment with abrocitinib worked in adults with AD compared to placebo (‘dummy treatment’) and a medicine that is already approved for AD, called dupilumab. The study showed that abrocitinib was better than placebo in improving the signs and symptoms of AD after 16 weeks. In addition, patients who were taking abrocitinib 200 mg for 2 weeks experienced greater relief from itch than patients who were taking abrocitinib 100 mg, placebo, or dupilumab. More people who took abrocitinib 200 mg reported side effects than those taking abrocitinib 100 mg, placebo, or dupilumab, but most of these side effects were mild or moderate. ClinicalTrials.gov NCT number: NCT03720470 .

Introduction Previous drug survival studies of dupilumab in atopic dermatitis (AD) show that many patients continue treatment through 1 year, suggesting that patients experience clinically relevant benefits with long-term treatment. Methods This post hoc analysis included data through week 100 from 391 adult patients from the dupilumab open-label extension (OLE) study who had not achieved the endpoints of at least 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) or an Investigator’s Global Assessment (IGA) score of 0 or 1 with short-term (16 weeks, 300 mg qw or q2w) dupilumab treatment in the parent SOLO 1 or 2 studies. All patients received dupilumab 300 mg qw in the OLE study, irrespective of whether they received qw or 2qw dosing in the parent study. Results Among those who had not achieved EASI-75 or IGA 0/1 during the 16-week parent study, the proportion of patients achieving EASI-75 by week 100 was 91%. The proportion achieving IGA 0 or 1 at week 100 was 45% for patients initially on q2w week dosing and 49% for those on initial qw dosing. Conclusion Long-term dupilumab treatment may be associated with improvement in AD in patients with suboptimal responses during the initial 16 weeks of treatment. Clinical Trial Registration LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743; EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769; EudraCT 2014-002619-40. LIBERTY AD OLE: ClinicalTrials.gov Identifier NCT01949311; EudraCT 2013-001449-15. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00643-4.

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. Most patients have an atopic predisposition. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution of the eczema; and (iii) chronic and chronically relapsing course. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Background: Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized.\ud \ud Objective: To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL.\ud \ud Methods: Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness.\ud \ud Results: Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 (p

Background: Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Objectives: To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety. Methods: A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo. Results: Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–

Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the T-helper 2 chemokine family. In Japan, serum TARC level has been commercially measured since 2008. After years of experience, we realized that TARC is an extremely useful clinical biomarker for atopic dermatitis (AD) treatment. Usually, physicians conduct a visual examination to determine whether their treatment has been successful; however, the visual examination results may not always be accurate; in such cases, serum TARC levels should be measured to eliminate any ambiguity regarding the treatment outcome. When the waning and waxing of eczema and fluctuations in the serum TARC levels were considered, we frequently found that AD does not follow a natural course but follows non-regulated inflammatory floating caused by insufficient intermittent topical treatment. Serum TARC is a promising biomarker for remission and can be used for accurately monitoring proactive treatment for long-term control. Abnormally high serum TARC levels indicate accelerated pathogenesis of cutaneous inflammation. Rapid normalization and maintaining normal serum TARC levels using appropriate topical treatment is a reasonable strategy for alleviating inflammation without upregulating cytokine expression. Observing serum TARC levels during early intervention for severe infantile AD is worthwhile to determine initial disease activity and evaluate treatment efficacy. Appropriate control of severe early-onset infantile AD is important for improving prognosis of eczema and for preventing food allergies. Additionally, this biomarker is useful for improving patient adherence. Dermatologists will be able to make great progress in treating AD by adopting biomarkers such as TARC for accurately assessing non-visible subclinical disorders.

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Itch (pruritus) is an unpleasant sensation that leads to the desire to scratch (1). Pruritus may compromise quality of life and sleep in affected individuals. Pruritus is simi -lar to pain, in being a subjective symptom; assessment of its intensity is a key issue in evaluating severity and therapeutic outcome of patients with pruritic disorders of diverse origins (cutaneous, systemic, neuropathic, psychogenic) (2). Various types of rating scales have been used and validated in the study of clinical itch, including the visual analogue scale (VAS), numerical rating scale, verbal rating scale, and behavioural rating scale (2–4). Among these measurement tools, the VAS seems to be one of the most commonly used methods of assessing pruritus severity, as it provides an easy and rapid estima -tion of itch (3, 4). The VAS is a 10-cm long line, oriented horizontally or vertically, on which patients indicate the intensity of pruritus by marking the line at the point that corresponds to the severity of their pruritus, where the beginning of the scale refers to no pruritus (0 point) and the end of the scale to the most severe pruritus (10 points) (3, 4). On behalf of the International Forum for the Study of Itch (IFSI), we discussed methodological problems of the VAS in clinical settings. During our discussion we identified that it is necessary to clarify the verbal expres-sion of the 10-point end, because it varies from study to study. It includes expressions such as “worst imaginable itch”, “the most severe pruritus they can imagine”, “most intense sensation imaginable”, “maximal itch”, “severe itching” and “unbearable pruritus” (3–8). In this report, we propose to consolidate the verbalization of extremes of VAS for “itch intensity” and “sleep disturbance (noc-turnal itch)”.CONSENSUS STATEMENTMembers of the Japanese Society for Dermatoallergo -logy and Contact Dermatitis (JSDACD) (MF, TE, AI, ST, YK, KT, TS, and HS) discussed possible core items for evaluating pruritus in clinical settings, including clinical trials, in Japan. Nine items were proposed and we evaluated the importance of each item by assigning a weight score (maximum points, 10) to each. The 2 highest-ranked items were “itch intensity” (score, 10