Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials
Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials
复制标题
三项随机、安慰剂对照 3 期试验中 Dupilumab 对中度至重度特应性皮炎成人不同种族亚组的疗效
DOI：
--
复制
发表时间：
2019
影响因子：
1.5
通讯作者：
M. Ardeleanu
中科院分区：
文献类型：
--
作者：
A. Alexis;M. Rendon;J. Silverberg;D. Pariser;B. Lockshin;C. Griffiths;J. Weisman;A. Wollenberg;Zhen Chen;John D. Davis;Meng Li;L. Eckert;A. Gadkari;B. Shumel;A. Rossi;N. Graham;M. Ardeleanu
Dupilumab是一种单抗，可以阻断白介素4和白介素13的共同受体亚单位，目前被批准用于治疗成人中重度特应性皮炎(AD)。DUPILUMA在种族亚群中治疗AD的有效性和安全性尚不清楚。这项来自三个第三阶段试验的事后分析根据种族亚组(白人、亚洲人、黑人/非裔美国人)评估了dupilumab与安慰剂的疗效和安全性。来自Liberty AD SOLO 1(NCT02277743)、SOLO 2(NCT02277769)和CHRONOS(NCT02260986)的数据被汇集在一起。结果包括从基线到第16周的关键治疗领域湿疹面积和严重指数(EASI)、峰值瘙痒数字评定量表(NRS)、皮肤病生活质量指数(DLQI)和以患者为导向的湿疹测量的平均和百分比变化，以及调查者的全球评估和欧洲生活质量-5维度3级问卷评估的疼痛或不适。
共有2,058名患者(白人n=1,429，亚裔n=501，黑人/非裔美国人n=128)被纳入本次分析。在治疗组和种族亚组之间，基线人口统计学和疾病特征是平衡的。在这三个试验中，dupiumab
在白人和亚洲亚组中，与安慰剂相比，显著(P<；0.0001)改善了所有评估结果。在规模较小的黑人/非裔美国人亚组中，Dupilumab显著(P<；0.0001)改善了EASI终点，与安慰剂相比，峰值瘙痒NRS和DLQI的平均变化，积极的数字趋势有利于所有其他终点的Dupilumab。
DUPILUMA总体上耐受性良好，在所有种族亚组中都具有可接受的安全性。服用安慰剂的患者发生严重不良事件的频率更高；在所有治疗组中，由于不良事件而中断治疗的情况都很少见。
在白人、亚洲人和黑人/非裔美国人种族亚群中，通过局部药物治疗未能充分控制中到重度AD的患者，使用dupilumab治疗可以显著改善临床状况，并获得良好的益处-风险曲线。
ClinicalTrials.gov标识：NCT02277743、NCT02277769、NCT02260986
Dupilumab, a monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, is currently approved for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis (AD). The efficacy and safety of dupilumab for AD among racial subgroups is unknown. This post hoc analysis from three phase 3 trials assessed the efficacy and safety of dupilumab vs placebo by racial subgroup (White, Asian, Black/African American). Data from LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02277769), and CHRONOS (NCT02260986) were pooled. Outcomes included mean and percent change from baseline to week 16 in the key therapeutic domains Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure, as well as Investigator’s Global Assessment and pain or discomfort assessed by the European Quality of Life-5 Dimensions 3 level questionnaire.
A total of 2,058 patients (White n=1,429, Asian n=501, Black/African American n=128) were included in the current analysis. Baseline demographics and disease characteristics were balanced between treatment groups and racial subgroups. In the three trials, dupilumab
significantly (P<0.0001) improved all assessed outcomes compared with placebo in the White and Asian subgroups. In the smaller Black/African American subgroup, dupilumab significantly (P<0.0001) improved EASI endpoints and mean changes in Peak Pruritus NRS and DLQI vs placebo, with positive numeric trends favoring dupilumab in all other endpoints.
Dupilumab was generally well tolerated, with an acceptable safety profile in all racial subgroups. Serious adverse events occurred more frequently with placebo; treatment discontinuations due to adverse events were rare in all treatment groups.
Significant clinical improvement and a favorable benefit-risk profile can be achieved with dupilumab treatment in patients of White, Asian, and Black/African American racial subgroups with moderate-to-severe AD inadequately controlled with topical medications.
ClinicalTrials.gov identifiers: NCT02277743, NCT02277769, NCT02260986