Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
J Eur Acad Dermatol Venereol. 2023 Dec;37(12):2558-2568. doi: 10.1111/jdv.19391. Epub 2023 Aug 26.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic eczematous lesions. The effect of treatment withdrawal after response to upadacitinib oral treatment is not fully characterized.
Assess the effect of upadacitinib withdrawal on skin clearance and itch improvement in adult patients with moderate-to-severe AD and evaluate the kinetics of recovery on rescue treatment.
Data from a phase 2b randomized, placebo-controlled trial (NCT02925117) of upadacitinib in patients with moderate-to-severe AD were analysed. Patients were randomized 1:1:1:1 to receive upadacitinib 7.5 mg, 15 mg, 30 mg or placebo, and then at Week 16, patients were re-randomized 1:1 to receive the same dose of upadacitinib (upadacitinib 30 mg for patients initialized to placebo) or placebo. From Week 20, those who experienced loss of response defined as Eczema Area and Severity Index <50% improvement from baseline (EASI 50) received rescue treatment with upadacitinib 30 mg.
Patients who withdrew from upadacitinib experienced a rapid loss of skin clearance response, while those who switched from placebo to upadacitinib gained response. Loss of skin clearance response occurred within 4 weeks and worsening of itch occurred within 5 days. In patients who originally received placebo or a lower dose of upadacitinib leading to a loss of EASI response, rescue treatment with upadacitinib 30 mg resulted in rapid recovery or improvement of both skin and itch responses; most patients who were re-randomized to placebo achieved EASI 75 and IGA 0/1 by 8 weeks of rescue treatment. No new safety risks were observed.
Continuous treatment with upadacitinib is suggested to maintain skin clearance and antipruritic effects.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其特征为瘙痒性湿疹样皮损。在对乌帕替尼口服治疗有反应后停止治疗的效果尚未完全确定。
评估乌帕替尼停药对中重度 AD 成年患者皮肤清除和瘙痒改善的影响，并评估在接受补救治疗时的恢复动力学。
对乌帕替尼治疗中重度 AD 的 2b 期随机、安慰剂对照试验（NCT02925117）的数据进行分析。患者以 1:1:1:1 的比例随机分配接受乌帕替尼 7.5mg、15mg、30mg 或安慰剂，然后在第 16 周，患者再次以 1:1 的比例随机分配接受相同剂量的乌帕替尼（对初始接受安慰剂的患者给予乌帕替尼 30mg）或安慰剂。从第 20 周开始，那些经历应答丧失（从基线 EASI 改善<50%定义为 EASI 50）的患者接受乌帕替尼 30mg 补救治疗。
从乌帕替尼停药的患者迅速失去皮肤清除应答，而从安慰剂转为乌帕替尼的患者获得应答。皮肤清除应答的丧失发生在 4 周内，瘙痒恶化发生在 5 天内。在最初接受安慰剂或较低剂量乌帕替尼导致 EASI 应答丧失的患者中，乌帕替尼 30mg 补救治疗导致皮肤和瘙痒应答迅速恢复或改善；大多数重新分配至安慰剂的患者在 8 周的补救治疗后达到 EASI 75 和 IGA 0/1。未观察到新的安全风险。
建议持续使用乌帕替尼治疗以维持皮肤清除和止痒效果。
