Silverberg Jonathan I, Hong H Chih-Ho, Calimlim Brian M, Lee Wan-Ju, 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). 2023 Oct;13(10):2247-2264. doi: 10.1007/s13555-023-01000-3. Epub 2023 Sep 1.
The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess 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.
Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181-1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis.
The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes.
Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient's personalized treatment plan.
中重度特应性皮炎（AD）的治疗方案不断扩展。这项网状Meta分析（NMA）更新了之前进行的NMA，纳入了最新3期试验的数据，以评估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，靶向全身治疗对中重度AD成人患者的相对疗效。
将lebrikizumab的近期3期单药治疗试验ADvocate1（NCT04146363）和ADvocate2（NCT04178967）的数据纳入分析，同时纳入通过Silverberg等人的系统文献综述确定的其他符合条件的3/4期随机安慰剂对照试验，这些试验涉及abrocitinib、baricitinib、度普利尤单抗、曲罗芦单抗和乌帕替尼。使用贝叶斯网状Meta分析评估达到湿疹面积和严重程度指数（EASI）较基线改善≥90%（EASI-90）、EASI较基线改善≥75%（EASI-75）、瘙痒数字评定量表较基线改善≥4分（ΔNRS≥4）以及研究者整体评估（IGA）评分为0或1（清除或几乎清除）且较基线降低≥2分（IGA 0/1）的患者比例。
更新后的NMA分析了13项独特的安慰剂对照试验，涉及6种靶向治疗的32个治疗组中的7105例患者。在主要时间点（第12周或16周）及更早时间点，乌帕替尼30mg在所有终点上都是最有效的治疗方法，通常其次是阿博利布200mg、乌帕替尼15mg、度普利尤单抗300mg以及lebrikizumab 250mg或阿博利布100mg。巴瑞替尼2mg和曲罗芦单抗在各结局中的排名通常较低。
AD的治疗选择需要考虑许多因素，尤其是随着新治疗方法不断涌现。纳入lebrikizumab近期的安慰剂对照3期数据后，在AD治疗12至16周期间，乌帕替尼30mg、乌帕替尼15mg和阿博利布200mg仍然是最有效的靶向全身治疗方法。这些更新的研究结果可为医疗保健提供者制定患者个性化治疗方案提供帮助。
