Efficacy of Upadacitinib and Dupilumab on Achieving Stringent and Composite Skin and Itch Outcomes: an Indirect Comparison of Adults with Moderate-to-Severe Atopic Dermatitis.

IF 3.5 3区医学 Q1 DERMATOLOGY Dermatology and Therapy Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI:10.1007/s13555-024-01240-x

April W Armstrong, H Chih-Ho Hong, Brian M Calimlim, Marric G Buessing, Marjorie M Crowell, Jonathan I Silverberg

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Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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中重度特应性皮炎患者的间接比较：Upadacitinib 和 Dupilumab 对实现严格和综合皮肤与瘙痒结果的疗效。

简介：包括Measure Up 1 (NCT03569293)、Measure Up 2 (NCT03607422)和Heads Up (NCT03738397)在内的试验对高达替尼的疗效进行了评估。Measure Up 1和2评估了达达替尼30毫克和达达替尼15毫克对安慰剂的疗效，而Heads Up则评估了达达替尼30毫克在头对头试验中对杜比鲁单抗300毫克的疗效。目前尚未进行奥达替尼 15 毫克与杜比鲁单抗 300 毫克的头对头试验。网络荟萃分析表明，达帕替尼 30 毫克和达帕替尼 15 毫克是疗效最好的系统性靶向治疗药物，但之前的间接比较并未评估更严格的结果：利用Measure Up 1和2以及Heads Up的个别患者数据进行了人群调整后间接比较，通过调整患者层面的协变量来估计如果将upadacitinib 15 mg纳入Heads Up，其疗效会如何。针对以下结果估算了第4、16和24周的绝对应答率：无痒/微痒[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%（EASI 90）和WP-NRS 0/1、EASI≤3和WP-NRS 0/1、EASI 100和WP-NRS 0/1。分析对象为成年患者，与临床试验的意向治疗人群一致，并采用非应答者归因法：结果：在所有评估结果中，达帕替尼 30 毫克的估计绝对应答率最高，其次是达帕替尼 15 毫克，然后是杜匹单抗。这一模式在第4周、第16周和第24周均有观察到：结论：对于中重度AD成人患者来说，在多个时间点获得更严格的综合疗效方面，奥达替尼30毫克似乎是最有效的治疗方法，其次是奥达替尼15毫克，然后是杜比鲁单抗300毫克。

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来源期刊

Dermatology and Therapy Medicine-Dermatology

CiteScore

6.00

自引率

8.80%

发文量

187

审稿时长

6 weeks

期刊介绍： Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.