Chu Alexandro W L, Wong Melanie M, Rayner Daniel G, Guyatt Gordon H, Díaz Martinez Juan Pablo, Ceccacci Renata, Zhao Irene X, McMullen Eric, Srivastava Archita, Wang Jason, Wen Aaron, Wang Fang Chi, Brignardello-Petersen Romina, Izcovich Ariel, Oykhman Paul, Wheeler Kathryn E, Wang Julie, Spergel Jonathan M, Singh Jasvinder A, Silverberg Jonathan I, Ong Peck Y, O'Brien Monica, Martin Stephen A, Lio Peter A, Lind Mary Laura, LeBovidge Jennifer, Kim Elaine, Huynh Joey, Greenhawt Matthew, Gardner Donna D, Frazier Winfred T, Ellison Kathy, Chen Lina, Capozza Korey, De Benedetto Anna, Boguniewicz Mark, Smith Begolka Wendy, Asiniwasis Rachel N, Schneider Lynda C, Chu Derek K
Department of Medicine, McMaster University, Hamilton, Canada; Evidence in Allergy Group, McMaster University, Hamilton, Canada.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
J Allergy Clin Immunol. 2023 Dec;152(6):1470-1492. doi: 10.1016/j.jaci.2023.08.029. Epub 2023 Sep 9.
Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes.
We sought to systematically synthesize the benefits and harms of AD systemic treatments.
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna).
The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain.
Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.
特应性皮炎（AD）是一种炎症性皮肤病，有多种全身治疗方法，且它们对AD结局的比较影响存在不确定性。
我们试图系统地综合AD全身治疗的益处和危害。
针对2023年美国过敏、哮喘与免疫学会以及美国过敏、哮喘和免疫学会联合实践参数特别工作组的AD指南，我们检索了MEDLINE、EMBASE、CENTRAL、科学网和GREAT数据库，检索时间从数据库建立至2022年11月29日，以查找针对AD全身治疗和光疗的随机试验。配对的评审员独立筛选记录、提取数据并评估偏倚风险。随机效应网络荟萃分析涉及AD严重程度、瘙痒、睡眠、AD相关生活质量、病情发作和危害。推荐评估、制定和评价方法为证据评级的确定性提供了依据。本综述已在开放科学框架（https://osf.io/e5sna）中注册。
纳入的149项试验（28686例中度至重度AD患者）评估了75种干预措施。有高确定性证据表明，高剂量乌帕替尼在6项对患者重要的结局中的5项中是最有效的药物之一；高剂量阿布昔替尼和低剂量乌帕替尼在2项结局中是最有效的药物之一。这些Janus激酶抑制剂在增加不良事件方面是危害最大的药物之一。有高确定性证据表明，度普利尤单抗、瑞莎珠单抗和曲罗芦单抗疗效中等且是最安全的药物之一，仅轻度增加结膜炎的发生。低剂量巴瑞替尼是疗效最差的药物之一。硫唑嘌呤、口服糖皮质激素、环孢素、甲氨蝶呤、霉酚酸酯、光疗和许多新型药物的疗效和安全性尚不确定。
在中度至重度AD患者中，高确定性证据表明，高剂量乌帕替尼在解决多项对患者重要的结局方面是最有效的药物之一，但也是危害最大的药物之一。高剂量阿布昔替尼和低剂量乌帕替尼有效，但也是危害最大的药物之一。度普利尤单抗、瑞莎珠单抗和曲罗芦单抗疗效中等且安全性良好。
