Background

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.

Objective

We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks.

Methods

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).

Results

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).

Conclusions

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.

中文翻译：

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Upadacitinib 加外用皮质类固醇治疗特应性皮炎：AD 第 52 周 Up 研究结果

背景

正在进行的 3 期双盲 AD Up 研究 (NCT03568318) 的主要（第 16 周）结果表明， upadacitinib + 局部皮质类固醇 (TCS) 在中度至重度特应性皮炎患者中具有积极的获益-风险特征。

客观的

我们在 52 周内评估了 upadacitinib + TCS 的疗效和安全性。

方法

患有慢性中度至重度特应性皮炎的 12 至 75 岁患者（≥10% 的体表面积受影响，湿疹面积和严重性指数 [EASI] ≥16，经验证的研究人员对特应性皮炎的全球评估 [vIGA-AD] ≥3和最差瘙痒数值评定量表 [WP-NRS] 评分≥4）按 1:1:1 随机分配至每日一次 upadacitinib 15 mg + TCS、upadacitinib 30 mg + TCS 或安慰剂 (PBO) + TCS（每周重新随机分组） 16 对 upadacitinib + TCS）。安全性和有效性，包括 EASI (EASI-75) 改善≥75%、vIGA-AD 清除/几乎清除且改善≥2 级 (vIGA-AD 0/1) 和 WP-NRS 改善≥4 的患者比例，通过第 52 周进行评估。缺失数据主要通过无响应插补处理，其中包括对 2019 年冠状病毒病 (COVID-19) 导致的缺失值的多重插补。

结果

在 901 名患者中，300 名被随机分配至 upadacitinib 15 mg + TCS，297 名被随机分配至 upadacitinib 30 mg + TCS，304 名被随机分配至 PBO + TCS。对于所有终点，upadacitinib 15 mg + TCS 和 upadacitinib 30 mg + TCS 在第 16 周的疗效维持至第 52 周。在第 52 周，接受 upadacitinib 15 mg + TCS 和 upadacitinib 30 mg + TCS 治疗的患者比例EASI-75 分别为 50.8% 和 69.0%；分别有 33.5% 和 45.2% 的人经历过 vIGA-AD 0/1；分别有 45.3% 和 57.5% 的 WP-NRS 改善≥4。Upadacitinib + TCS 在 52 周内耐受良好；没有观察到超出当前标签的新的重要安全风险。没有死亡报告；主要不良心血管事件和静脉血栓栓塞事件很少发生（≤0.2/100 患者年）。

结论

通过 52 周的结果表明 upadacitinib + TCS 在中度至重度 AD 患者中的疗效和良好的安全性长期维持。