Silverberg Jonathan I, Hong H Chih-Ho, Thyssen Jacob P, Calimlim Brian M, Joshi Avani, Teixeira Henrique D, Collins Eric B, Crowell Marjorie M, Johnson Scott J, Armstrong April W
Department of Dermatology, The George Washington University School of Medicine and Health Sciences, 2150 Pennsylvania Ave NW, Ste 2B-425, Washington, DC, 20037, USA.
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
Dermatol Ther (Heidelb). 2022 May;12(5):1181-1196. doi: 10.1007/s13555-022-00721-1. Epub 2022 Apr 18.
The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.
The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis.
Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily.
Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment.
Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD.
尚未利用近期的3期数据系统评估靶向全身治疗对中度至重度特应性皮炎（AD）的疗效。这项网状Meta分析评估了在不添加外用糖皮质激素（TCS）和/或外用钙调神经磷酸酶抑制剂（TCI）的情况下，靶向全身治疗对中度至重度AD成人患者的相对疗效。
系统文献综述检索了截至2021年5月17日的3/4期试验，这些试验将乌帕替尼、白细胞介素-4（IL-4）、白细胞介素-13（IL-13）或JAK抑制剂与安慰剂或活性干预措施进行比较，受试对象为对TCS/TCI反应不足或TCS/TCI在医学上不适用的中度至重度AD成人和青少年，对年份或地区没有限制。研究人员使用PRISMA指南评估数据。采用贝叶斯网状Meta分析评估达到试验共同主要终点的患者比例[研究者整体评估（IGA）评分为0或1（清除或几乎清除）且较基线降低≥2分；达到湿疹面积和严重程度指数（EASI）较基线改善≥75%（EASI-75）的患者比例]；EASI较基线改善≥90%（EASI-90）；以及瘙痒数字评定量表较基线改善≥4分（ΔNRS≥4）。
在最初识别的3415条记录中，网状Meta分析（NMA）最终纳入了6条记录，代表9项独特的研究。两项乌帕替尼试验也被纳入。对包括6254例患者的11项临床试验进行了分析。在主要终点（第12周或16周）以及更早的时间点，每日30 mg乌帕替尼是所有终点中最有效的治疗方法，其次是每日15 mg乌帕替尼和每日200 mg阿布昔替尼。
AD的治疗选择需要考虑许多因素。这些发现有助于医疗保健提供者为患者制定个性化治疗方案。
在AD治疗的12 - 16周内，每日30 mg乌帕替尼（upadacitinib）、每日15 mg乌帕替尼和每日200 mg阿布昔替尼（abrocitinib）可能是最有效的靶向全身治疗方法。
