Silverberg Jonathan I, Thyssen Jacob P, Lazariciu Irina, Myers Daniela E, Güler Erman, Chovatiya Raj
Department of Dermatology The George Washington University School of Medicine and Health Sciences Washington District of Columbia USA.
Department of Dermatology Bispebjerg Hospital University of Copenhagen Copenhagen Denmark.
Skin Health Dis. 2024 May 5;4(4):e382. doi: 10.1002/ski2.382. eCollection 2024 Aug.
Patients with atopic dermatitis (AD) exhibit heterogeneous clinical phenotypes, reflecting different combinations of itch and lesional severity. AD with severe itch but clear-moderate lesions, also known as itch-dominant AD, is a common clinical phenotype.
To evaluate abrocitinib efficacy in patients with moderate-to-severe AD who have itch-dominant AD.
This post hoc analysis includes pooled data from clinical trials of patients with moderate-to-severe AD receiving abrocitinib (100 or 200 mg) as monotherapy (phase 2b; phase 3 JADE MONO-1 and JADE MONO-2) or in combination with topical therapy (phase 3 JADE COMPARE). Data from the ongoing long-term JADE EXTEND trial (data cutoff April 2020) were also evaluated. Itch-dominant AD was defined as baseline Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7-10 and Investigator's Global Assessment of 0-3 or Eczema Area and Severity Index of 0‒21. Assessments included a ≥4-point improvement in PP-NRS (PP-NRS4), PP-NRS score of 0 (no itch) or 1 (little itch) in patients with PP-NRS score ≥2 at baseline, ≥4-point improvement from baseline in Patient-Oriented Eczema Measure (POEM-4), Patient Global Assessment (PtGA) of clear or almost clear, and Dermatology Life Quality Index (DLQI) score of 0 or 1 (no impact or little impact of AD on quality of life [QoL]).
In the pooled monotherapy trials, 37% of patients had itch-dominant AD at baseline. As early as Week 2, more patients with itch-dominant AD achieved PP-NRS4 with abrocitinib 100 mg (35%) and abrocitinib 200 mg (57%) versus placebo (7%); 6% and 22% versus 0%, respectively, achieved PP-NRS 0/1. More patients achieved a PtGA of clear/almost clear at Week 12 with abrocitinib 100 mg (28%) and abrocitinib 200 mg (45%) than placebo (9%). Additionally, abrocitinib led to clinically meaningful improvements in POEM and DLQI. Most patients with itch-dominant AD experienced itch improvement over time with abrocitinib monotherapy or with concomitant topical therapy; 86%-87% and 62%-67% of patients had no itch-moderate itch and clear-moderate lesions by weeks 24 and 48, respectively.
Abrocitinib is highly efficacious in patients with itch-dominant AD, demonstrating rapid, deep, and sustained improvements in itch and clinically meaningful improvements in patients' QoL.
NCT02780167; NCT03349060; NCT03575871; NCT03720470; NCT03422822.
特应性皮炎(AD)患者表现出异质性临床表型,反映了瘙痒和皮损严重程度的不同组合。严重瘙痒但皮损为轻至中度的AD,也称为瘙痒主导型AD,是一种常见的临床表型。
评估阿布昔替尼对瘙痒主导型中重度AD患者的疗效。
这项事后分析纳入了接受阿布昔替尼(100或200mg)单药治疗(2b期;3期JADE MONO-1和JADE MONO-2)或联合局部治疗(3期JADE COMPARE)的中重度AD患者临床试验的汇总数据。还评估了正在进行的长期JADE EXTEND试验(数据截止于2020年4月)的数据。瘙痒主导型AD定义为基线时瘙痒峰值数字评定量表(PP-NRS)评分为7-10,研究者整体评估为0-3或湿疹面积和严重程度指数为0-21。评估指标包括PP-NRS改善≥4分(PP-NRS4)、基线时PP-NRS评分≥2的患者PP-NRS评分为0(无瘙痒)或1(轻微瘙痒)、患者导向性湿疹测量指标(POEM)较基线改善≥4分(POEM-4)、患者整体评估(PtGA)为清除或几乎清除,以及皮肤病生活质量指数(DLQI)评分为0或1(AD对生活质量[QoL]无影响或影响极小)。
在汇总的单药治疗试验中,37%的患者基线时为瘙痒主导型AD。早在第2周,与安慰剂组(7%)相比,100mg阿布昔替尼组(35%)和200mg阿布昔替尼组(57%)有更多瘙痒主导型AD患者实现了PP-NRS4;实现PP-NRS 0/1的患者分别为6%、22%和0%。在第12周时,100mg阿布昔替尼组(28%)和200mg阿布昔替尼组(45%)实现PtGA为清除/几乎清除的患者多于安慰剂组(9%)。此外,阿布昔替尼使POEM和DLQI有临床意义的改善。大多数瘙痒主导型AD患者通过阿布昔替尼单药治疗或联合局部治疗,瘙痒随时间推移得到改善;在第24周和第48周时,分别有86%-87%和62%-67%的患者无瘙痒-中度瘙痒且皮损为清除-中度。
阿布昔替尼对瘙痒主导型AD患者高度有效,在瘙痒方面显示出快速、深度和持续的改善,并使患者的QoL有临床意义的改善。
NCT02780167;NCT03349060;NCT03575871;NCT03720470;NCT03422822。