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Dupilumab is prescribed in one dosage across adult atopic dermatitis patients. Differences in drug exposure may explain variation in treatment response. Investigating the clinical relevance of dupilumab serum concentration in atopic dermatitis in real-world practice. In two centers (Netherlands, UK), adults treated with dupilumab for atopic dermatitis were evaluated for effectiveness and safety pretreatment and at 2, 12, 24, and 48 weeks; trough serum samples were analyzed for dupilumab concentration at corresponding time points. In 149 patients, median dupilumab levels during follow-up ranged from 57.4 to 72.4 μg/mL. Levels showed high inter-patient and low intra-patient variability. No correlation was found between levels and ΔEASI. At 2 weeks, levels of ≥64.1 μg/mL predict EASI ≤7 at 24 weeks (specificity:100%, sensitivity:60%; p =.022). At 12 weeks, ≤32.7 μg/mL predicts EASI >7 at 24 weeks (sensitivity:95%, specificity:26%; p =.011). Inverse correlations were found between baseline EASI and levels at 2, 12, and 24 weeks (r = −0.25 to 0.36; p ≤.023). Low levels were particularly observed in patients with adverse events, treatment interval deviation, and discontinuation. At the on-label dosage, the measured range of dupilumab levels does not seem to yield differences in treatment effectiveness. However, disease activity does seem to influence dupilumab levels - higher baseline disease activity results in lower levels at follow-up. [ABSTRACT FROM AUTHOR]

Elderly-onset atopic dermatitis (AD) is a remarkable subtype and has been put on the agenda owing to its difficulty to control. Understanding the influence of genetic and environmental exposures is crucial to preventing elderly-onset AD. To explore the association between genes and air pollution on incident elderly-onset AD. This study was based on UK Biobank that recruited over 500,000 participants. The genetic risks were categorized into low, intermediate, and high groups according to tertiles of polygenic risk scores. Mixed exposure to various air pollutants was assessed using the weighted quantile sum (WQS) and also categorized based on tertiles. Within each genetic risk group, whether air pollutant mixture was associated with incident elderly-onset AD was estimated. 337,910 participants were included in the final analysis, and the mean age was 57.1. The median years for follow-up were 12.0, and the incident cases of AD were 2545. The medium and high air pollution mixture was significantly associated with incident AD compared with the low pollution group, with HRs of 1.182 (P = 0.003) and 1.359 (P < 0.001), respectively. In contrast, HR for medium and high genetic susceptibility was only 1.065 (P = 0.249) and 1.153 (P = 0.008). The population-attributable fraction of air pollution and genetic risk was 15.5 % (P < 0.001) and 6.4 % (P = 0.004). Additionally, compared with low genetic risk and low air pollution, high genetic risk and high air pollution was significantly associated with the incidence of elderly-onset AD with a HR of up to 1.523 (P < 0.001). There were no interactive effects between each group of genetic risks and air pollution. When grouped by sex, females could observe a stronger effect by genetic and air pollutant mixture exposure. Air pollution and genetics both independently enhance the risk of newly developed AD, and the effect of air pollutants is stronger than the investigated genes. • The effect of air pollutant mixtures on incident AD was examined. • Exposure to air pollutants has a larger contribution than genetic variants. • Air pollution is associated with AD independent of genetic susceptibility. [ABSTRACT FROM AUTHOR]