Department of Dermatology, Preventive Medicine and Medical Social Sciences, Northwestern University Feinberg School of Medicine, NMH/Arkes Family Pavilion Suite, 1600, 676 N. Saint Clair, Chicago, IL, 60611, U.S.A.
Department of Dermatology, Oregon Health & Science University, Portland, OR, U.S.A.
Br J Dermatol. 2019 Jul;181(1):80-87. doi: 10.1111/bjd.17791. Epub 2019 Apr 11.
In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab.
To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life.
LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769.
At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36·0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (-48·9% vs. -11·3%, P < 0·001), pruritus NRS (-35·2% vs. -9·1%, P < 0·001), affected BSA (-23·1% vs. -4·5%, P < 0·001), POEM score ≥ 4-point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4-point improvement (59·3% vs. 24·4%, P < 0·001).
In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.
在美国，针对特应性皮炎（AD）的注册临床试验，监管结局的标准衡量指标是研究者全球评估（IGA）评分≤1（即清除或几乎清除皮肤），包括支持最近批准度普利尤单抗的临床试验。
使用其他验证的 AD 体征、症状和生活质量的评估措施，评估度普利尤单抗治疗 IGA＞1 的患者在治疗结束时的治疗效果。
LIBERTY AD SOLO 1 和 2 是两项为期 16 周、随机、双盲试验，纳入了中度至重度 AD（IGA≥3）、经局部治疗控制不佳的成年患者。我们对接受度普利尤单抗 300mg 每 2 周（q2w）或安慰剂治疗的患者进行了一项事后分析。IGA＞1 的患者的评估措施包括湿疹面积和严重程度指数（EASI）、瘙痒数字评分量表（NRS）、受累体表面积（BSA）、患者导向湿疹测量（POEM）和皮肤病生活质量指数（DLQI）。这些试验在 ClinicalTrials.gov 注册：NCT02277743 和 NCT02277769。
在 449 名接受度普利尤单抗 q2w 治疗的患者中，有 278 名（中位年龄 36.0 岁）和 443 名接受安慰剂治疗的患者在第 16 周时 IGA＞1。在第 16 周 IGA＞1 的患者中，与安慰剂相比，度普利尤单抗显著改善了多项评估措施：EASI（-48.9% vs.-11.3%，P＜0.001）、瘙痒 NRS（-35.2% vs.-9.1%，P＜0.001）、受累 BSA（-23.1% vs.-4.5%，P＜0.001）、POEM 评分≥4 分改善（57.4% vs.21.0%，P＜0.001）和 DLQI 评分≥4 分改善（59.3% vs.24.4%，P＜0.001）。
在第 16 周 IGA＞1 的患者中，与安慰剂相比，度普利尤单抗诱导了在多个验证的评估措施中具有统计学意义的获益。IGA≤1 的终点显著低估了度普利尤单抗治疗的临床相关效果。
