期刊
ALLERGY
卷 78, 期 6, 页码 1554-1569出版社
WILEY
DOI: 10.1111/all.15647
关键词
atopic dermatitis; biomarker; endotype; interleukin-13; tralokinumab
This study found that many patients with mild-to-moderate atopic dermatitis have elevated levels of biomarkers, suggesting a systemic impact of skin inflammation. Identifying different patient subtypes can better predict their response to specific treatments.
BackgroundThe heterogeneous (endo)phenotypes of atopic dermatitis (AD) require precision medicine. Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI) >= 16. Previous studies have demonstrated an improved treatment response to the anti-interleukin (IL)-13 antibody tralokinumab in AD subgroups with elevated levels of the IL-13-related biomarkers dipeptidyl-peptidase (DPP)-4 and periostin. MethodsHerein, 373 AD patients aged >= 12 years were stratified by IL-13(high), periostin(high) and DPP-4(high) endotypes using cross-sectional data from the ProRaD cohort Bonn. High was defined as >80th quantile of 47 non-atopic controls. We analyzed endotype-phenotype associations using machine-learning gradient boosting compared to logistic regression. ResultsAtopic dermatitis severity and eosinophils correlated with IL-13 and periostin levels. Correlations of IL-13 with EASI were stronger in patients with increased (rs = 0.482) than with normal (rs = 0.342) periostin levels. We identified eosinophilia >6% and an EASI range of 5.5-17 dependent on the biomarker combination to be associated with increasing probabilities of biomarker(high) endotypes. Also patients with mild-to-low-moderate severity (EASI < 16) featured increased biomarkers (IL-13(high): 41%, periostin(high): 48.4%, DPP-4(high): 22.3%). Herthoge sign (adjusted Odds Ratio (aOR) = 1.89, 95% Confidence Interval (CI) [1.14-3.14]) and maternal allergic rhinitis (aOR = 2.79-4.47) increased the probability of an IL-13(high)-endotype, dirty neck (aOR = 2.83 [1.32-6.07]), orbital darkening (aOR = 2.43 [1.08-5.50]), keratosis pilaris (aOR = 2.21 [1.1-4.42]) and perleche (aOR = 3.44 [1.72-6.86]) of a DPP-4(high)-endotype. ConclusionsA substantial proportion of patients with EASI < 16 featured high biomarker levels suggesting systemic impact of skin inflammation already below the current cut-off for systemic therapy. Our findings facilitate the identification of patients with distinct endotypes potentially linked to response to IL-13-targeted therapy.
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