Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC.
National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, Netherlands.
J Allergy Clin Immunol. 2022 Mar;149(3):977-987.e14. doi: 10.1016/j.jaci.2021.07.036. Epub 2021 Aug 14.
Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis.
We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks.
Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19).
Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years).
Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.
正在进行的 3 期、双盲 AD Up 研究（NCT03568318）的主要（第 16 周）结果表明，乌帕替尼联合局部皮质类固醇（TCS）在中重度特应性皮炎患者中具有积极的获益风险比。
我们通过 52 周评估了乌帕替尼的疗效和安全性。
年龄在 12 至 75 岁之间的慢性中重度特应性皮炎（≥10%的身体表面积受影响，湿疹面积和严重程度指数[EASI]≥16，特应性皮炎验证性研究者全球评估[vIGA-AD]≥3，以及最严重瘙痒数字评分量表[WP-NRS]评分≥4）患者随机分为 1:1:1 接受每日一次乌帕替尼 15 mg+TCS、乌帕替尼 30 mg+TCS 或安慰剂（PBO）+TCS（第 16 周重新随机分组至乌帕替尼+TCS）。通过第 52 周评估安全性和疗效，包括 EASI-75 改善≥75%的患者比例（EASI-75）、vIGA-AD 改善≥2 级且为清晰/几乎清晰（vIGA-AD 0/1）和 WP-NRS 改善≥4 的患者比例。由于 COVID-19，缺失数据主要通过非应答插补处理，对于缺失值采用多重插补。
在 901 例患者中，300 例患者随机分配至乌帕替尼 15 mg+TCS 组，297 例患者随机分配至乌帕替尼 30 mg+TCS 组，304 例患者随机分配至 PBO+TCS 组。所有终点均显示，乌帕替尼 15 mg+TCS 和乌帕替尼 30 mg+TCS 在第 16 周的疗效在第 52 周时得到维持。第 52 周时，乌帕替尼 15 mg+TCS 和乌帕替尼 30 mg+TCS 治疗的患者中，EASI-75 的比例分别为 50.8%和 69.0%；vIGA-AD 0/1 的比例分别为 33.5%和 45.2%；WP-NRS 改善≥4 的比例分别为 45.3%和 57.5%。乌帕替尼+TCS 在 52 周内耐受性良好；未观察到超出当前标签的新的重要安全性风险。未报告死亡事件；主要不良心血管事件和静脉血栓栓塞事件罕见（≤0.2/100 患者年）。
第 52 周的结果表明，乌帕替尼+TCS 在中重度 AD 患者中具有长期的疗效维持和良好的安全性。
