特应性皮炎（AD）前沿文献精读特辑（J Allergy Clin Immunol Pract / J Dermatol / Allergy / Dermatol Ther (Heidelb)）

The integration of research discoveries into routine clinical care is often slow and resource-intensive, particularly in allergy and immunology, where advances in biologics, immunotherapy, precision diagnostics, and guideline-driven management continue to evolve rapidly. Implementation science provides a structured approach to understand and address the gaps between research discovery and real-world patient care. In asthma, food allergy, atopic dermatitis, drug allergy, and primary immune disorders, variation in clinician knowledge, health system infrastructure, reimbursement models, patient demographics, and staffing patterns contribute to inconsistent uptake of evidence-based interventions. Implementation science offers tools to systematically evaluate these contextual factors and develop strategies that improve adoption, fidelity, sustainability, and equity in allergic and immunologic care. By offering theory-informed frameworks to design, adapt, and evaluate interventions across diverse clinical settings, implementation science advances the study of evidence-to-practice care gaps in allergy and immunology. When applied thoughtfully, these methods enhance implementation of specialty guidelines, practice parameters, and emerging therapies, while addressing multilevel determinants of care delivery. With the rapidly growing application of precision medicine and augmented intelligence to allergy and immunology practice, the study of how to best apply technological and research discovery to clinical practice will be needed to promote equitable uptake of evidence-based care.

BACKGROUND: Atopic dermatitis (AD) is characterized by microbial dysbiosis, notably an overabundance of Staphylococcus species. This study aimed to evaluate the effects of abrocitinib, a Janus kinase 1-selective inhibitor, on the skin microbiome and clinical outcomes in patients with moderate-to-severe AD. METHODS: Patients enrolled in JADE MOA (NCT03915496) were randomly assigned to receive once-daily abrocitinib (100 or 200 mg) or placebo for 12 weeks. Skin swabs collected at baseline and Weeks 2, 4, and 12 underwent 16S rRNA gene amplicon sequencing to determine microbial composition. Disease severity was assessed at the same time points using established clinical metrics. Associations between microbial abundance and clinical metrics, as well as inflammatory and skin barrier markers, were investigated. RESULTS: Data from 43 patients were included. Alpha diversity increased significantly at Week 12 of treatment with abrocitinib 200 mg. Beta diversity analysis revealed clustering of the abrocitinib groups away from placebo as early as Week 2; divergence continued through Week 12. Staphylococcus and S. aureus relative abundance decreased in a dose-dependent manner from Week 2 through Week 12 of abrocitinib treatment. Changes in skin microbial composition corresponded with improvements in clinical metrics of disease severity as well as immune markers of AD. CONCLUSIONS: Abrocitinib treatment is associated with beneficial changes in the skin microbiome, notably a reduction in S. aureus and increased microbial diversity. These findings provide insight into the mechanism of action of abrocitinib and the interplay of immunomodulation and the skin microbiome in AD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03915496.

INTRODUCTION: Baseline severity of atopic dermatitis (AD) may influence treatment response. The objective of this analysis was to assess short- and long-term abrocitinib efficacy and safety by baseline AD severity. METHODS: A post-hoc analysis of patients (aged ≥ 12 years) with moderate-to-severe AD receiving abrocitinib 100 mg or 200 mg or placebo in two studies-JADE COMPARE (ClinicalTrials.gov ID: NCT03720470) and JADE EXTEND (NCT03422822)-was performed. Baseline severity was assessed by several measures, including the Investigator's Global Assessment (IGA) and the Eczema Area and Severity Index (EASI). Efficacy and safety endpoints were stratified by baseline severity. RESULTS: Higher proportions of patients with moderate or severe baseline AD achieved IGA score 0/1 (clear/almost clear) with abrocitinib at week 16 (moderate: 40.8% [100 mg], 50.0% [200 mg]; severe: 19.1% [100 mg], 43.2% [200 mg]) versus placebo (moderate: 18.0%; severe: 2.8%). At week 112, IGA 0/1 was achieved by high proportions of patients receiving abrocitinib with moderate (60.2% [100 mg], 64.3% [200 mg]) or severe (38.6% [100 mg], 54.5% [200 mg]) disease. Response rates were similar with other measures, including co-achievement of EASI-90 (90% improvement from baseline score) and Peak Pruritus Numerical Rating Scale 0/1 (no itch/mild itch). There were no new safety signals. CONCLUSION: Abrocitinib demonstrated early and sustained improvement in skin clearance and itch through week 112 in adult and adolescent patients, and sustained responses were observed in patients in the moderate and severe baseline AD subgroups. CLINICAL TRIALS REGISTRATION: This study was a pooled analysis of data from the phase 3 JADE COMPARE (NCT03720470) and JADE EXTEND (NCT03422822) trials.