The clinical relevance of dupilumab serum concentration in patients with atopic dermatitis: a two-center prospective cohort study

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%; <i>p</i> = .022). At 12 weeks, ≤32.7 μg/mL predicts EASI &gt;7 at 24 weeks (sensitivity:95%, specificity:26%; <i>p</i> = .011). Inverse correlations were found between baseline EASI and levels at 2, 12, and 24 weeks (<i>r</i> = −0.25 to 0.36; <i>p</i> ≤ .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.

度普利尤单抗（dupilumab）为成人特应性皮炎患者的统一给药剂量方案。药物暴露量的差异或可解释治疗应答的异质性。本研究旨在探讨真实世界临床实践中，dupilumab血清浓度在特应性皮炎患者中的临床相关性。
本研究在荷兰、英国两家医学中心开展，纳入接受dupilumab治疗的成人特应性皮炎患者，于治疗前及治疗第2、12、24、48周评估其临床疗效与安全性，并在对应时间点采集谷浓度血清样本以分析dupilumab的血清浓度。
本研究共纳入149例患者，随访期间dupilumab的中位血清浓度介于57.4~72.4 μg/mL之间。患者间药物浓度差异显著，而个体内变异度较低，未观察到血清浓度与湿疹面积和严重程度指数变化值（ΔEASI）存在相关性。
治疗第2周时，血清浓度≥64.1 μg/mL可预测患者在第24周时的湿疹面积和严重程度指数（EASI）评分≤7（特异性100%，敏感性60%，*p*=0.022）；治疗第12周时，血清浓度≤32.7 μg/mL可预测患者在第24周时的EASI评分＞7（敏感性95%，特异性26%，*p*=0.011）。
基线EASI评分与治疗第2、12、24周的血清药物浓度呈负相关（*r*=-0.25~-0.36，*p*≤0.023）。在出现不良事件、治疗间隔偏离方案及提前停药的患者中，dupilumab血清浓度尤其偏低。
在说明书推荐剂量下，本研究测得的dupilumab血清浓度范围似乎未对治疗疗效产生显著影响。然而，疾病活动度确实会影响dupilumab的血清浓度——基线疾病活动度越高，随访期间的药物浓度越低。