二村 昌樹

Clinical remission in asthma has gained prominence as both a therapeutic goal and a research endpoint, although its operational definitions have varied. To harmonize Japanese practice with emerging global frameworks, the Japanese Society of Allergology (JSA) conducted a two-round modified Delphi survey to establish a consensus definition for inclusion in the 2024 Asthma Prevention and Management Guidelines (JGL 2024). In Round 1 (January 2024), 81 JGL 2024 guideline committee members representing adult and pediatric specialties were invited. Seventy-four percent agreed that clinical remission should be defined, and 50 % supported including both on- and off-treatment remission. Four core components emerged: absence of exacerbations, well-controlled symptoms, no continuous oral corticosteroid use, and optimization of pulmonary function. Round 2 refined operational thresholds for symptom control, adopting ACT ≥23 (C-ACT ≥23 for children) and ACQ ≤0.75, consistent with JGL's long-standing goal of achieving a truly symptom-free state without reliever use. Pulmonary function was defined as "optimization," encompassing normalization where achievable and stabilization when normalization is unlikely (e.g., airway remodeling), which received strong agreement. Collaboration between adult and pediatric experts affirmed clinical remission as a milestone toward off-treatment remission and potential cure, broadening its applicability across severities and age groups. This review further summarizes evidence supporting remission as an outcome of biologic therapy, its key predictors (e.g., smoking, obesity, disease duration), pediatric perspectives, and future directions. JGL 2024 formally adopts these criteria, providing a rigorous and pragmatic framework to advance patient-centered asthma care and reframe management toward disease modification and eventual cure.

Topical molecular targeted therapies have recently emerged for the treatment of atopic dermatitis (AD), but their efficacy and safety, particularly in children, remain underexplored. This systematic review and meta-analysis aim to evaluate the efficacy and safety of topical targeted therapies in children with AD. We conducted a comprehensive search of the CENTRAL, MEDLINE, Embase, and ICHUSHI databases for articles published up to January 7, 2023, based on a protocol registered in PROSPERO (CRD42022366449). Randomized controlled trials (RCTs) investigating new topical targeted therapies in children (≤18 years) with AD were included. The primary outcomes were the Eczema Area and Severity Index (EASI) scores and treatment-related adverse events. Secondary outcomes included additional efficacy and safety analyses. A meta-analysis was performed using Revman 5.4, with bias risk assessed via the RoB 2 tool. Nine studies (reported in eight articles) involving 2182 patients were included, with 1469 children treated with Janus kinase inhibitors (ruxolitinib and delgocitinib) and phosphodiesterase-4 inhibitors (crisaborole, lotamilast, and difamilast). These interventions significantly improved EASI scores, with the least square mean change (mean difference: -56.67%; 95% confidence interval [-59.16% to -54.18%]). Additionally, topical targeted therapies did not increase the incidence of treatment-emergent adverse events (risk difference: 0.00; 95% confidence interval [-0.02 to 0.02]). The risk of bias was low across all outcomes. New topical targeted therapies administered over 4 weeks are effective and safe for children with atopic dermatitis aged ≤18 years. Further studies are needed to establish their long-term safety and efficacy.

BACKGROUND: In recent years, several targeted therapeutic options have become available for the management of atopic dermatitis in children. In this systematic review and meta-analysis, we assessed the efficacy and safety of systemic targeted therapies for atopic dermatitis in children. METHODS: A systematic review of literature available in CENTRAL, MEDLINE, Embase, and ICHUSHI databases until January 7, 2023, was performed. Randomized controlled trials of systemic targeted therapies (biologics and small molecules) on children aged 18 years or younger with atopic dermatitis were included. The primary outcomes were the eczema area and severity index (EASI) and adverse events. Other efficacy and safety outcomes were also used for meta-analysis and risk of bias analysis. RESULTS: We included 10 studies reported in 11 articles involving three agents (dupilumab, abrocitinib, and upadacitinib) and 1760 children. Systemic targeted therapies significantly improved eczema severity with an EASI-75 response (risk ratio, 2.99; 95 % confidence interval [CI], 2.66-3.37). However, systemic targeted therapies were associated with treatment-emergent adverse events (risk difference, 0.05; 95 % CI, 0.01-0.09), particularly among small molecules in subgroup analysis, while no such trend was observed with biologics. Systemic targeted therapy also significantly improved other efficacy outcomes, and no significant association was found in the other safety outcomes. There was no risk of bias in any of the outcomes. CONCLUSIONS: Our findings indicate that systemic targeted therapies are effective and relatively safe for treating atopic dermatitis in children, although small molecules may pose a slightly higher risk of adverse events.

BACKGROUND: This study examined the relationship between the disciplinary diversity of research teams and research output (RO) in allergy and immunology programs funded by the National Institutes of Health (NIH) in the United States, Medical Research Council (MRC) in the United Kingdom, and Japan Society for the Promotion of Science (JSPS). METHODS: Using a dataset containing 1243, 3645, and 1468 articles funded by the NIH, MRC, and JSPS, respectively, we analyzed the correlation between disciplinary diversity and RO in allergy and immunology programs that received grants from 2017 to 2021. Diversity was measured using All Science Journal Classification codes counts, Shannon-Wiener index, and newly developed Omnidisciplinary index (o-index). The impact of diversity on RO was evaluated Normalized Paper Count (reflecting research quantity), Normalized Top 1% Paper Count (reflecting research excellence), and Normalized Top 10% Paper Count (reflecting research substantiality). RESULTS: There were no significant differences in diversity between the funding agencies, indicating a marginal relationship between team composition and RO (p = 0.641 for Shannon-Winner index). RO was positively correlated with team diversity in NIH- and MRC-funded programs and positively correlated with the degree of specialization in JSPS-funded programs. CONCLUSIONS: These results underscore the complexity of the relationship between research team diversity and RO and the influence of contextual factors such as country-specific characteristics and grant program objectives. Specifically, the analysis of JSPS-funded groups suggests that the degree of specialization has a greater impact on RO than disciplinary diversity. This study contributes to ongoing efforts to optimize team composition to improve RO in allergy and immunology programs.

BACKGROUND: Hay fever (HF) presents with various symptoms, including allergic conjunctivitis and rhinitis, and requires cross-organ treatment. This study assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HF treatment trends. METHODS: This retrospective cohort study utilized data from the JMDC database collected between January 2018 and May 2021. Patients with HF were identified based on the relevant International Classification of Diseases 10th Revision diagnosis codes and the prescription of HF-related medications. The treatment approaches were compared during the cedar and cypress pollen allergy season (January to May in Japan) before and during the COVID-19 pandemic (2018 and 2019, and 2020 and 2021, respectively). RESULTS: This study included 2,598,178 patients with HF. The numbers of prescribed HF-related claims in 2018, 2019, 2020, and 2021 were 3,332,854, 3,534,198, 2,774,380, and 2,786,681 times, respectively. Oral second-generation antihistamine prescriptions decreased by >10% from 2019 to 2020, with a <10% change in the subsequent year. Anti-allergic eye drop prescriptions also decreased by >10% from 2019 to 2020 but increased by >10% from 2020 to 2021. Compared with 2018, 2019, and 2020, the number of claims in the rhinitis symptoms dominant group was significantly decreased in 2021 (p < 0.001, all). In contrast, the number of claims in the eye symptoms dominant group and the rhinitis and eye symptoms dominant group increased in 2021 compared with that in 2018, 2019, and 2020 (p < 0.001, all). CONCLUSION: Changes in HF treatment and related outcomes could be attributed to lifestyle modifications resulting from the COVID-19 pandemic. Measures, such as limiting outdoor activities and adopting mask-wearing practices may have influenced HF symptoms, preventive behaviors, and the overall approach to treating HF.

BACKGROUND: In the enhancement of allergy care involving multidisciplinary and multiple medical departments, there is a perceived need for education that targets not only specialists but also non-specialists. However, research on the need for and methods of such education remains inadequate. OBJECTIVE: To design a remote allergy care education program for all medical practitioners and to validate its necessity and utility. METHODS: The Empowering Next Generation Allergist/immunologist toward Global Excellence Task Force (ENGAGE-TF), supported by the Japanese Society of Allergology, initiated a virtual educational program called 'Outreach Lectures' in collaboration with Keio University and Fukui University. This initiative was widely promoted through social media and various institutions, and a survey was conducted through its mailing list. RESULTS: 1139 responses were obtained. More than half were physicians from non-allergy specialties, representing a diverse range of healthcare professions. Over 70% expressed being 'very satisfied,' and over 60% found the difficulty level 'appropriate.' Free-form feedback revealed differences in learning focus based on profession and learning approach based on years of experience. CONCLUSION: The high participation rate (90%) of non-specialist physicians underscores the demand for addressing allergic conditions in primary care. The effectiveness of virtual / recurrent education, particularly for healthcare professionals with over 11 years of experience, was implied. Further follow-up investigation focusing on quantitative and objective assessment of educational effectiveness is indispensable.

BACKGROUND: In 2022, the "New Capitalism Grand Design and Implementation Plan" was adopted in Japan, emphasizing the promotion and environmental development of startups. Given this context, an investigation into the startup and investment landscape in the allergy sector, both domestically and internationally, becomes imperative. METHODS: We analyzed 156 allergy-related startups from Japan, the US, and Europe from 2010 to 2021. Data on corporate information and investment trends were extracted from databases and VC websites. RESULTS: The total investment reached approximately 7.2 billion USD, with a ratio of 20:6:1 for the US, Europe, and Japan, respectively. The US showed a decline post its peak from 2016-2018, while Europe and Japan experienced growth. Notably, the US primarily invested in biopharmaceuticals for atopic dermatitis and food allergies, Europe in asthma-related apps, and Japan in healthcare apps and cross-border startups. DISCUSSION AND CONCLUSION: While Japan's investment environment in the allergy sector remains in its nascent stages and has room for development, the US and Europe are evidently ahead. Considering the rise of startups and funding limitations in Japan, external funding from regions like the US becomes a potential avenue. These findings are anticipated to contribute to the strategic activation of startups in allergy research and development.

Abstract Background Atopic dermatitis (AD) is a chronic, inflammatory skin condition affecting up to one-quarter of children. Uncontrolled pruritus associated with childhood AD, and the accompanying scratching, negatively impacts quality of life (QoL), sleep and development. The humanized monoclonal antibody nemolizumab, used concomitantly with topical agents, was shown to reduce pruritus and improve QoL in patients with AD aged ≥ 13 years. However, data relating to its efficacy and safety in younger children (aged &amp;lt; 13 years) have been lacking. Objectives To evaluate the efficacy and safety of nemolizumab, administered concomitantly with topical agents, in Japanese paediatric patients (aged 6–12 years) with AD and inadequately controlled moderate-to-severe pruritus. Methods This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre, 16-week, phase III study. Patients aged ≥ 6 and &amp;lt; 13 years, with confirmed AD, and an inadequate pruritic response despite treatment with topical agents and oral antihistamines were randomly assigned (1 : 1) to receive nemolizumab 30 mg or placebo every 4 weeks (Q4W). The primary efficacy endpoint was the change in the weekly mean 5-level itch score from baseline to week 16; secondary efficacy endpoints were related to pruritus, indicators for AD and QoL. Safety was assessed via adverse events (AEs) and laboratory test results. Results In total, 89 patients were enrolled, received either nemolizumab 30 mg (n = 45) or placebo (n = 44) Q4W, and completed the study. The mean patient age was 9.1 (SD 1.9) years, and mean duration of AD was 8.5 (2.7) years. The change in 5-level itch score from baseline to week 16 showed a statistically significant difference in the nemolizumab treatment group (−1.3) compared with placebo (−0.5; least-squares mean difference −0.8, 95% confidence interval −1.1 to −0.5; P &amp;lt; 0.0001). Improvements with nemolizumab were observed from the second day of administration. Secondary endpoints were in favour of nemolizumab. No AEs resulted in discontinuation, and the overall safety profile in patients aged 6–12 years was comparable with that in older patients (aged ≥ 13 years) with AD. Conclusions Nemolizumab is a potential new treatment option for paediatric patients with AD whose pruritus has not been sufficiently improved with topical treatments and antihistamines.

IMPORTANCE: Egg introduction in infants at age 4 to 6 months is associated with a lower risk of immunoglobulin E-mediated egg allergy (EA). However, whether their risk of EA at age 12 months is affected by maternal intake of eggs at birth is unknown. OBJECTIVE: To determine the effect of maternal egg intake during the early neonatal period (0-5 days) on the development of EA in breastfed infants at age 12 months. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, single-blind (outcome data evaluators), randomized clinical trial was conducted from December 18, 2017, to May 31, 2021, at 10 medical facilities in Japan. Newborns with at least 1 of 2 parents having an allergic disease were included. Neonates whose mothers had EA or were unable to consume breast milk after the age of 2 days were excluded. Data were analyzed on an intention-to-treat basis. INTERVENTIONS: Newborns were randomized (1:1) to a maternal egg consumption (MEC) group, wherein the mothers consumed 1 whole egg per day during the first 5 days of the neonate's life, and a maternal egg elimination (MEE) group, wherein the mothers eliminated eggs from their diet during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was EA at age 12 months. Egg allergy was defined as sensitization to egg white or ovomucoid plus a positive test result in an oral food challenge or an episode of obvious immediate symptoms after egg ingestion. RESULTS: Of the 380 newborns included (198 [52.1%] female), 367 (MEC: n = 183; MEE: n = 184) were followed up for 12 months. On days 3 and 4 after delivery, the proportions of neonates with ovalbumin and ovomucoid detection in breast milk were higher in the MEC group than in the MEE group (ovalbumin: 10.7% vs 2.0%; risk ratio [RR], 5.23; 95% CI, 1.56-17.56; ovomucoid: 11.3% vs 2.0%; RR, 5.55; 95% CI, 1.66-18.55). At age 12 months, the MEC and MEE groups did not differ significantly in EA (9.3% vs 7.6%; RR, 1.22; 95% CI, 0.62-2.40) or sensitization to egg white (62.8% vs 58.7%; RR, 1.07; 95% CI, 0.91-1.26). No adverse effects were reported. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, EA development and sensitization to eggs were unaffected by MEC during the early neonatal period. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000027593.

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of 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. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. 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.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of 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. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. 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.