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Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives: To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study -demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods: The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged =12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results: Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion: Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab was equally effective among all racial subgroups in clinical trials, but a direct comparison in daily practice is lacking. Objectives: To investigate the effectiveness of dupilumab in patients with atopic dermatitis (AD) in the Netherlands and Japan over 80 weeks of treatment. Methods: A longitudinal comparative cohort study was conducted in patients with AD who were treated with dupilumab in daily practice. We used linear mixed‐effects models to determine changes over time. Results: We found statistically significant differences in sex, disease onset, body mass index and therapeutic history between Dutch (n = 208) and Japanese (n = 153) patients. The baseline Eczema Area and Severity Index (EASI) score was higher in Japanese patients (23·8 vs. 14·8), while baseline Patient‐Reported Outcome Measures (PROMs) were higher in Dutch patients. EASI scores decreased quickly to a level indicating 'mild disease' (EASI < 7), and remained low in both countries. However, PROMs showed different trajectories with better scores in Japan. Conclusions: Dupilumab showed significant, comparable and sustained improvement of EASI scores in Japanese and Dutch patients. However, we found striking differences in the effect on PROMs between the countries, with a better outcome in Japanese patients. What is already known about this topic?In clinical trials, dupilumab was found to be equally effective among all racial subgroups; however, a direct comparison in daily practice between patients with atopic dermatitis (AD) in Japan and the Netherlands is currently lacking.Although phenotypical and immunological differences between races are described for AD, literature about the racial differences in coping mechanisms and the perception of disease in AD is lacking. What does this study add? This study showed a significant improvement of disease severity in both Japanese and Dutch patients with AD during dupilumab treatment in daily practice.In addition to racial disease‐specific differences, healthcare system‐ or culture‐related characteristics might contribute to differences in physician‐ and patient‐reported outcome measures (PROMs) between countries. What are the clinical implications of the work? Consideration of PROMs and healthcare system‐ or culture‐related characteristics, in addition to disease severity measures including the Eczema Area and Severity Index, is of added value in the evaluation of treatment effectiveness in clinical studies and in daily practice. Linked Comment: A. Taïeb and N. Katoh. Br J Dermatol 2021; 185:479–480. [ABSTRACT FROM AUTHOR]

Dear Editor, Fish allergy (FA) is the second most frequent type of food allergy in Japan.[1] Fish allergens listed in the database of the World Health Organization include parvalbumin, which is known to be the major allergen, -enolase, aldolase A, vitellogenin and tropomyosin.[2] Patients with atopic dermatitis (AD) have an increased risk for sensitization to allergens because of their increased skin barrier permeability.[3] Here, we enrolled six patients with FA, who had also been diagnosed with AD according to the diagnostic criteria of the Japanese guidelines.[4] A table summarizing the clinical details of the patients and controls is available on request from the authors. All the patients showed immediate-type responses, such as urticaria or anaphylaxis, upon eating fish and had positive results on skin prick tests and/or serum IgE reactivity with CAP for fish allergens. The expected allergen recognized by the patient's IgE but not by the control IgE was a protein of approximately 230 kDa at a I pI i of 4-5-6-0 (Fig. b, c). [Extracted from the article]

Linked Article:de Wijs et al. Br J Dermatol 2021; 185:555–562. [ABSTRACT FROM AUTHOR]

Linked Article: Kabashima et al. Br J Dermatol 2022; 186:642–651. Atopic dermatitis is an inflammatory skin condition that affects up to 25% of children and 5% of adults worldwide. Itch is a common symptom of atopic dermatitis. The itch–scratch cycle associated with atopic dermatitis affects sleep and daily activities, and causes extreme distress to patients. Nemolizumab is a new drug that has been shown to reduce the severity of itch when given in combination with topical treatments (treatments that are applied directly to the skin). This study, from Japan, aimed to find out if nemolizumab can continuously reduce itch over a long period of time (more than 1 year). Information obtained from patients enrolled in two clinical trials of nemolizumab was examined. Patients in both trials continued to use their usual skin ointments/creams throughout. We found that nemolizumab was able to reduce itch and the symptoms of eczema for up to 68 weeks. Sleep and quality of life were also improved. Importantly, in the 8 weeks after stopping treatment, most patients did not report acute itchiness or a flare up of their atopic dermatitis. In addition, this study shows that nemolizumab was safe to use over this long treatment period. The results support the long‐term use of nemolizumab in patients with atopic dermatitis who have not been able to get adequate relief using topical treatment or oral antihistamines. Linked Article: Kabashima et al. Br J Dermatol 2022; 186:642–651. [ABSTRACT FROM AUTHOR]

Background Mutations in the gene encoding filaggrin ( FLG) have been shown to predispose to atopic eczema (AE). Objectives Further to establish population genetics of FLG mutations in the Japanese population and to elucidate effects of FLG mutations to filaggrin biosynthesis in skin of patients with AE. Methods We searched for FLG mutations in 19 newly recruited Japanese patients with AE. We then screened 137 Japanese patients with AE and 134 Japanese control individuals for a novel mutation identified in the present study. In addition, we evaluated FLG mRNA expression by real-time reverse transcription–polymerase chain reaction and profilaggrin/filaggrin protein expression by immunohistochemical staining in the epidermis of the patients carrying the novel mutation. Results We identified a novel FLG nonsense mutation c.12069A>T (p.Lys4021X) in one patient with AE. Upon further screening, p.Lys4021X was identified in four patients with AE (2·9% of all the patients with AE). In total, there are at least eight FLG variants in the Japanese population. Here we show that about 27% of patients in our Japanese AE case series carry one or more of these eight FLG mutations and these variants are also carried by 3·7% of Japanese general control individuals. There is a significant statistical association between the eight FLG mutations and AE (χ2 P = 6·50 × 10−8). Interestingly, the present nonsense mutation is in the C-terminal incomplete filaggrin repeat and is the mutation nearest the C-terminal among previously reported FLG mutations. Immunohistochemical staining for filaggrin revealed that this nonsense mutation leads to remarkable reduction of filaggrin protein expression in the patients’ epidermis. Conclusions We clearly demonstrated that FLG mutations are significantly associated with AE in the Japanese population. The present results further support the hypothesis that the C-terminal region is essential for proper processing of profilaggrin to filaggrin. [ABSTRACT FROM AUTHOR]

Although there have been several reports on the prevalence of atopic dermatitis (AD) in Japanese schoolchildren based on questionnaires, there has been no nation-wide study of the frequency of this condition diagnosed by dermatologists in regular health check-ups of schoolchildren.The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check-ups by dermatologists.In 2001/2, elementary schoolchildren: first graders (age 6–7 years) and sixth graders (age 11–12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700 × 4 × 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease.The point prevalence of AD was 11·2% overall (2664 of 23 719) ranging from 7·4% (Iwate) to 15·0% (Fukuoka) in the eight areas. Seventy-four per cent, 24%, 1·6% and 0·3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11·8% vs. 10·5%,P < 0·01). There was no apparent difference in prevalence between urban and rural districts, or between boys and girls.The prevalence of AD in Japanese elementary schoolchildren was about 10%, three-quarters of those being mildly affected. This is the first nation-wide study made of Japanese elementary schoolchildren examined by dermatologists to evaluate the frequency of AD. [ABSTRACT FROM AUTHOR]

Summary Background The incidence of atopic dermatitis (AD) has increased in Japan, along with the number of patients with severe and treatment-resistant AD in urban and industrial areas. We hypothesize that these changes could be due to increased reactive oxygen species (ROS) generated from environmental pollution and solar radiation. Objectives To demonstrate whether direct oxidative protein damage of the stratum corneum of the biopsied skin from AD patients is increased when compared with controls. Patients and methods Carbonyl moieties in skin biopsies from 75 patients with AD were assessed using both spectrophotometric and immunohistochemical detection of the formation of dinitrophenylhydrazone (DNP) from dinitrophenylhydrazine (DNPH). These were compared with diseased and normal controls. Lipid peroxidation was also assessed by staining with antibody to 4-hydroxy-2-nonenal (4-HNE), an aldehyde product of oxidized ω-6-fatty acids. In addition, the activity of superoxide dismutase (SOD), an effective scavenger of ROS, was assessed and compared with controls. Results The level of protein carbonyl moieties in patients' skin was elevated and correlated directly with the severity of the disease. In contrast, DNP formation was not significantly increased in diseased controls, when compared with healthy volunteers, and no statistical significance was found between the two control groups. SOD activity was increased except for those with extra-severe disease. Positive staining with anti-DNP antibody and anti-4-HNE antibody were found in the most superficial layers of the stratum corneum. Conclusions This study has found an association between AD severity and markers of ROS-associated damage, adding weight to the hypothesis that environmentally generated ROS may induce oxidative protein damage in the stratum corneum, leading to the disruption of barrier function and exacerbation of AD. [ABSTRACT FROM AUTHOR]

Summary Background Adult atopic dermatitis (AD) in Japan has become a significant social problem, with as many as one-third of adult patients with severe AD absenting themselves from work or classes due to aggravation of the disease. Reports of such patients have become increasingly common in recent years. Despite the pressing need for epidemiological studies to clarify the prevalence and distribution of AD and to determine its aetiology, no previous research has been carried out on the prevalence of AD within the adult population in Japan. Objectives To clarify the prevalence of adult AD in Japan, using the U.K. Working Party's diagnostic criteria. Methods The subjects of this study were mostly government officials or their family members visiting the Medical Center of Health Science, Toranomon Hospital in Tokyo for annual health check-ups in the period from September 1997 to August 1998. Questionnaires completed by 10 762 persons (8076 men and 2686 women) aged 30 years or above were analysed. The questionnaire consisted of 14 questions on allergic disease. The U.K. Working Party's diagnostic criteria were used after translation into Japanese. Three types of prevalence were used as indicators of prevalence: point, 1-year and lifetime prevalence. Results The point prevalence, 1-year prevalence and lifetime prevalence of AD in Japanese adults were 2·9%, 3·0% and 3·3%, respectively. No significant statistical differences were observed between the sexes or among age groups within each sex. The survey indicated that 88·6% of those who had ever had AD were currently affected by active AD, while 93·4% of those who had had at least one episode of AD in the past had experienced an episode over the previous year. Conclusions This study gives the first indication of the prevalence of adult AD among the Japanese, based on the U.K. criteria. Both the internal and external validity of this study are believed to be high; it would be safe to conclude... [ABSTRACT FROM AUTHOR]

Background The authors have carried out questionnaire surveys of health symptoms in school children (aged 7–12 years) in Osaka Prefecture, Japan. In this study, the geographical distribution of and trends in the prevalence of atopic dermatitis were evaluated. Objectives To assess the relationship between the prevalence of atopic dermatitis in children and the environmental factors, and to estimate future changes of the prevalence of atopic dermatitis. Methods A total of seven population surveys were carried out at 2-year intervals between 1985 and 1997 in a total of about 4 million primary school children (460 000–740 000 per survey). Results The lifetime prevalence of atopic dermatitis increased from 15·0% in 1985 to 24·1% in 1993 but levelled off thereafter. According to the school year, the prevalence was higher in lower-year pupils. However, the prevalence stopped rising earlier in lower-year pupils and began to decrease in 1997 in first- to third-year pupils. The prevalence according to areas was significantly correlated negatively with air pollution and positively with the income index. According to the income classes, the prevalence increased until 1993 but levelled off thereafter in all classes, which reduced the differences among the classes. Conclusions The increase of the prevalence of atopic dermatitis in school children stopped in 1993 in Osaka Prefecture, Japan. It is conceivable that the prevalence had reached the saturation level. [ABSTRACT FROM AUTHOR]

Focuses on the polymorphisms related to adult atopic dermatitis (AD) in Japan. Association of Gln551arg with AD; Importance of including interleukin-4 receptor α chain as candidate gene for AD; Etiology of the disease.

Linked Article: Thomas et al. Br J Dermatol 2021; 185:139–146. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international collaboration involving people with eczema, health professionals, researchers, regulators and industry representatives. The collaboration is working globally to agree a defined list of aspects of eczema that should be measured in all future eczema clinical trials and systematic reviews. At previous international consensus meetings, collaborators have agreed what aspects of eczema (also called dermatitis) are important to capture, and how clinical signs of eczema and eczema symptoms should be measured. The HOME VII consensus meeting, held in Japan in April 2019, involved 74 participants from around the world and aimed to agree how best to measure quality of life, long‐term eczema control and itch intensity. Following whole and small group discussions and anonymous keypad voting over 3 days, agreement was reached on the preferred measurement instruments to be used to capture patient‐reported outcomes of quality of life, eczema control and itch intensity. For now, the core outcome set for clinical trials in atopic eczema is complete and can be used by researchers around the world to improve consistency in clinical trial design and allow evidence to be combined from different studies more easily. This should help ensure that clinical care is based on the best available evidence. Linked Article: Thomas et al. Br J Dermatol 2021; 185:139–146. [ABSTRACT FROM AUTHOR]

The article presents a retrospective study of patients with moderate to severe atopic dermatitis (AD) who were treated and followed up in the Division of Allergy, National Center for Child Health and Development in Tokyo, Japan. It aims to investigate whether proactive treatment, the long-term, low-dose intermittent application of anti-inflammatory agents to previously affected skin together with daily application of emollients, changes serum immunoglobulin (Ig) E levels.

Atopic dermatitis (AD), a long‐lasting skin disease characterized by intense itching and dry, red, swollen and cracked skin, affects between 2% and 10% of Japanese adults. In Japan, patients with moderate‐to‐severe or very severe AD have limited treatment options, most with unwanted side effects. There is a need for therapies that provide safe and effective long‐term control. The underlying mechanism of AD may differ between Asian and Western patients, and this study aimed to evaluate dupilumab, a drug that blocks key molecules that cause AD, in Japanese patients with moderate‐to‐severe AD. The authors studied Japanese patients from three international, placebo‐controlled clinical trials of dupilumab. Of the 1,597 adults with moderate‐to‐severe AD in those trials ("all patients"), 250 were Japanese. The investigators measured the effects of dupilumab treatment for 16 weeks or one year on the signs (what a clinician observes) and symptoms (what a patient feels) of AD. At the start of each trial, Japanese patients generally had more severe AD than all patients. Nevertheless, dupilumab significantly improved signs and symptoms of AD (including itch) compared with placebo (dummy drug) in the Japanese patients and was as well tolerated in the Japanese patients as in all patients; dupilumab was more likely than placebo to be associated with injection‐site reaction or conjunctivitis ("pinkeye"). Compared with placebo, dupilumab reduced the amount of substances in the blood that are generally increased in patients with AD. The investigators concluded that, similar to all patients, dupilumab is effective and well tolerated in Japanese patients with moderate‐to‐severe AD. Linked Article: Katoh et al. Br J Dermatol 2020; 183:39–51. [ABSTRACT FROM AUTHOR]

Analyzes the dermatological manifestations of HIV seropositive patients in Japan. Skin diseases associated with HIV; Decrease in the number of eosinophils in the peripheral blood; Criteria for the diagnosis of atopic dermatitis.

Criticizes a study on incidence of hypertension in a Japanese adult population with atopic dermatitis. Determination of the annual costs of illness; Identification of patients through claims histories.