Armstrong April W, Hong H Chih-Ho, Calimlim Brian M, Buessing Marric G, Crowell Marjorie M, Silverberg Jonathan I
Division of Dermatology, University of California Los Angeles, Los Angeles, CA, USA.
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
Dermatol Ther (Heidelb). 2024 Sep;14(9):2457-2465. doi: 10.1007/s13555-024-01240-x. Epub 2024 Jul 30.
Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30 mg and upadacitinib 15 mg against placebo, while Heads Up assessed efficacy of upadacitinib 30 mg in a head-to-head trial against dupilumab 300 mg. A head-to-head trial of upadacitinib 15 mg against dupilumab 300 mg has not been conducted. Network meta-analysis has shown that upadacitinib 30 mg and upadacitinib 15 mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes.
A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation.
Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24.
For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15 mg and then dupilumab 300 mg.
在包括“Measure Up 1”（NCT03569293）、“Measure Up 2”（NCT03607422）和“Heads Up”（NCT03738397）在内的试验中评估了乌帕替尼的疗效。“Measure Up 1”和“Measure Up 2”评估了30毫克乌帕替尼和15毫克乌帕替尼对比安慰剂的疗效，而“Heads Up”在一项头对头试验中评估了30毫克乌帕替尼对比300毫克度普利尤单抗的疗效。尚未进行15毫克乌帕替尼对比300毫克度普利尤单抗的头对头试验。网络荟萃分析表明，30毫克乌帕替尼和15毫克乌帕替尼是最有效的靶向全身治疗药物之一，但之前的间接比较未评估更严格的结局。
使用来自“Measure Up 1”、“Measure Up 2”和“Heads Up”的事后个体患者数据进行人群校正间接比较，通过调整患者水平协变量来估计如果15毫克乌帕替尼纳入“Heads Up”试验其表现如何。针对以下结局估计第4周、第16周和第24周的绝对缓解率：无/轻微瘙痒[最差瘙痒数字评定量表（WP-NRS）评分为0/1]、湿疹面积和严重程度指数（EASI）评分≤3（EASI≤3）、EASI改善100%（EASI 100）、EASI改善≥90%且WP-NRS为0/1、EASI≤3且WP-NRS为0/1，以及EASI 100且WP-NRS为0/1。该分析针对成年患者进行，与临床试验的意向性治疗人群一致，并采用无反应者插补法。
在所有评估的结局中，估计的绝对缓解率以30毫克乌帕替尼最高，其次是15毫克乌帕替尼，然后是度普利尤单抗。在第4周、第16周和第24周均观察到这种模式。
对于中度至重度特应性皮炎成人患者，30毫克乌帕替尼似乎是在多个时间点实现更严格和综合结局方面最有效的治疗方法，其次是15毫克乌帕替尼，然后是300毫克度普利尤单抗。
