Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
JAMA Dermatol. 2023 Mar 1;159(3):255-266. doi: 10.1001/jamadermatol.2022.6192.
Erythrodermic atopic dermatitis (AD) is a severe AD subtype defined by extensive skin involvement, leading to complications and sometimes hospitalization.
To assess dupilumab's efficacy and safety in patients with erythrodermic AD in clinical trials.
DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis included patients enrolled in 6 multicenter, multinational, randomized, double-blind, placebo-controlled trials. Patients included in this analysis met erythrodermic AD criteria of 90% or greater body surface area (BSA) affected by AD and Global Individual Sign Score for erythema of 1 or higher. Data analyses for this post hoc analysis were conducted between March 5, 2019, and October 24, 2020.
Dupilumab once weekly or every 2 weeks, or placebo, either as monotherapy or with concomitant topical corticosteroids (TCS).
Efficacy (BSA, Eczema Area and Severity Index [EASI] score, Peak Pruritus Numerical Rating Scale [PP-NRS] score), changes in serum biomarkers (thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase), and safety (incidence of adverse events) at week 16. Data were pooled within each regimen; monotherapy and concomitant TCS results are shown separately.
Of 3075 randomized patients, 209 met criteria for erythrodermic AD at baseline, with the median age being 31 and 39 years in the monotherapy and concomitant TCS trials, respectively, similar to the overall populations (34 and 36 years, respectively); 71.3% (n = 97) and 74.0% (n = 54) of patients, respectively, were male (compared with 58.7% and 60.6% in the overall populations). In patients with erythrodermic AD, dupilumab once weekly and every 2 weeks vs placebo significantly improved percentage of BSA affected by AD (least squares mean percent change [SE]) with monotherapy (-42.0% [7.7%] and -39.9% [6.5%] vs -17.2% [11.0%]; P = .03) and concomitant TCS (-63.2% [6.7%] and -56.1% [9.1%] vs -14.5% [7.3%]; P < .001); EASI score with monotherapy (-58.5% [9.0%] and -58.3% [7.9%] vs -22.3% [12.4%]; P = .004 and P = .003, respectively) and concomitant TCS (-78.9% [7.8%] and -70.6% [10.1%] vs 19.3% [8.2%]; P < .001); and PP-NRS score in monotherapy (-45.9% [7.8%] and -33.9% [6.6%] vs -0.6% [9.4%]; P < .001) and concomitant therapy (-53.0% [8.1%] and -55.7% [10.8%] vs -26.0% [8.8%]; P = .006 and P = .01, respectively). Nominally statistically significant improvement was seen as early as week 1 (EASI and PP-NRS scores with monotherapy). Biomarker levels were significantly reduced vs placebo. The most frequent adverse events in dupilumab-treated patients were injection-site reaction, conjunctivitis, and nasopharyngitis.
In this post hoc analysis of 6 randomized clinical trials, treatment with dupilumab resulted in rapid, sustained improvements in AD signs and symptoms with acceptable safety in patients with erythrodermic AD, similar to those in the trials' overall patient population.
ClinicalTrials.gov Identifiers: NCT01859988, NCT02277743, NCT02277769, NCT03054428, NCT02260986, NCT02755649.
重要性：红皮病型特应性皮炎（AD）是一种严重的 AD 亚型，其特征为广泛的皮肤受累，导致并发症，有时需要住院治疗。
目的：评估度普利尤单抗在临床试验中对红皮病型 AD 患者的疗效和安全性。
设计、地点和参与者：本事后分析包括 6 项多中心、多国、随机、双盲、安慰剂对照试验中入组的患者。符合红皮病型 AD 标准的患者，体表面积（BSA）受累≥90%，红斑全球个体评分（EASI）为 1 或更高。这项事后分析的数据于 2019 年 3 月 5 日至 2020 年 10 月 24 日之间进行分析。
干预措施：度普利尤单抗每周或每 2 周 1 次，或安慰剂，单药治疗或联合局部皮质类固醇（TCS）。
主要结果和措施：第 16 周时的疗效（BSA、EASI 评分、瘙痒峰值数字评定量表 [PP-NRS] 评分）、血清生物标志物（胸腺和激活调节趋化因子、总免疫球蛋白 E、乳酸脱氢酶）的变化，以及不良事件（发生率）。每个方案内汇总数据；分别显示单药治疗和联合 TCS 的结果。
结果：在 3075 名随机患者中，209 名患者在基线时符合红皮病型 AD 的标准，单药治疗和联合 TCS 试验的中位年龄分别为 31 岁和 39 岁，与总体人群（分别为 34 岁和 36 岁）相似；分别有 71.3%（97 名）和 74.0%（54 名）的患者为男性（而总体人群中分别为 58.7%和 60.6%）。在红皮病型 AD 患者中，与安慰剂相比，度普利尤单抗每周和每 2 周 1 次治疗可显著改善 AD 受累 BSA 的百分比（最小二乘均数变化 [SE]），单药治疗时为-42.0%（7.7%）和-39.9%（6.5%），安慰剂为-17.2%（11.0%）（P=0.03）；联合 TCS 时为-63.2%（6.7%）和-56.1%（9.1%），安慰剂为-14.5%（7.3%）（P<0.001）；EASI 评分在单药治疗时为-58.5%（9.0%）和-58.3%（7.9%），安慰剂为-22.3%（12.4%）（P=0.004 和 P=0.003），联合 TCS 时为-78.9%（7.8%）和-70.6%（10.1%），安慰剂为 19.3%（8.2%）（P<0.001）；PP-NRS 评分在单药治疗时为-45.9%（7.8%）和-33.9%（6.6%），安慰剂为-0.6%（9.4%）（P<0.001），联合 TCS 时为-53.0%（8.1%）和-55.7%（10.8%），安慰剂为-26.0%（8.8%）（P=0.006 和 P=0.01）。在单药治疗时，EASI 和 PP-NRS 评分在第 1 周就出现了显著改善。生物标志物水平显著降低。度普利尤单抗治疗患者中最常见的不良事件是注射部位反应、结膜炎和鼻咽炎。
结论和相关性：在这项 6 项随机临床试验的事后分析中，在红皮病型 AD 患者中，与安慰剂相比，度普利尤单抗治疗可迅速、持续改善 AD 体征和症状，安全性可接受，与试验总体患者人群相似。
试验注册：ClinicalTrials.gov 标识符：NCT01859988、NCT02277743、NCT02277769、NCT03054428、NCT02260986、NCT02755649。
