Silverberg Jonathan I, Bunick Christopher G, Hong H Chih-Ho, Mendes-Bastos Pedro, Stein Gold Linda, Costanzo Antonio, Ibrahim Nadia, Sancho Cristina, Wu Xiaoqiang, Han Yu, Levy Gweneth, Altman Kathy, Calimlim Brian, Eyerich Kilian
Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Department of Dermatology and Program in Translational Biomedicine, Yale University, New Haven, CT, USA.
Br J Dermatol. 2024 Dec 23;192(1):36-45. doi: 10.1093/bjd/ljae404.
Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients with AD continue to experience flares and substantial clinical burden, despite ongoing systemic treatment.
To assess the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) as per its label, and present the week 16 primary analysis results.
Level Up is a phase IIIb/IV global randomized open-label efficacy assessor-blinded study evaluating UPA vs. DUPI in adolescents and adults with moderate-to-severe AD who had an inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (period 1). Patients on UPA were started on 15 mg and dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥ 4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on or after week 4, or an EASI reduction of at least 75% (EASI 75) on or after week 8. The primary endpoint was simultaneous achievement of an EASI reduction of at least 90% (EASI 90) and WP-NRS 0/1 at week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study.
Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at week 16 was demonstrated with UPA vs. DUPI (19.9% vs 8.9%, respectively; P < 0.001). UPA showed superiority over DUPI for all ranked secondary endpoints, with post hoc analyses exhibiting higher itch response rates as early as day 2. No new safety signals were identified in this period.
Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose-escalated based on clinical response, demonstrated superiority over DUPI per its label for the primary endpoint of simultaneous achievement of near-complete skin clearance (EASI 90) and little-to-no itch (WP-NRS 0/1) at week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. No new safety signals were identified vs. the previously reported safety profiles of UPA and DUPI.
特应性皮炎（AD）是一种慢性皮肤病，其特征为剧烈瘙痒和湿疹样皮肤病变。尽管进行了持续的全身治疗，但一些AD患者仍会出现病情发作并承受巨大的临床负担。
评估每日一次服用乌帕替尼（UPA）（起始剂量为15mg，并根据临床反应将剂量递增至30mg）与按照其标签使用的度普利尤单抗（DUPI）相比的疗效和安全性，并展示第16周的主要分析结果。
“升级”研究是一项IIIb/IV期全球随机开放标签疗效评估者设盲研究，在对全身治疗反应不佳或不宜使用全身治疗的中度至重度AD青少年和成人中评估UPA与DUPI。患者被随机分配至UPA或DUPI组进行16周的治疗（第1阶段）。服用UPA的患者起始剂量为15mg，如果在第4周及以后未实现湿疹面积和严重程度指数（EASI）降低至少50%（EASI 50）或最差瘙痒数字评定量表（WP-NRS）改善≥4分，或在第8周及以后未实现EASI降低至少75%（EASI 75），则将剂量递增至30mg。主要终点是在第16周同时实现EASI降低至少90%（EASI 90）和WP-NRS为0/1。排序后的次要终点包括不同反应水平和时间点的皮肤和瘙痒反应。在整个研究过程中评估安全性指标。
与DUPI相比，UPA在第16周实现EASI 90和WP-NRS 0/1同时反应方面显示出更高的疗效（分别为19.9%和8.9%；P<0.001）。在所有排序后的次要终点上，UPA均显示出优于DUPI，事后分析显示早在第2天瘙痒反应率就更高。在此期间未发现新的安全信号。
对于中度至重度AD患者，起始剂量为15mg并根据临床反应递增剂量的UPA治疗，在第16周实现接近完全的皮肤清除（EASI 90）和几乎无瘙痒（WP-NRS 0/1）这一主要终点方面，显示出优于按照其标签使用的DUPI，所有排序后的次要终点在不同的皮肤和瘙痒反应水平及时间点均显示出优势。与先前报道的UPA和DUPI安全性概况相比，未发现新的安全信号。
