Schneeweiss Maria C, Glynn Robert J, Wyss Richard, Anand Priyanka, Jin Yinzhu, Landon Joan, Mostaghimi Arash, Merola Joseph F, Silverberg Jonathan I, Rosmarin David M, Sidbury Robert, Schneeweiss Sebastian
Dermato-Pharmacoepidemiology Work Group, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
Dermato-Pharmacoepidemiology Work Group, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
J Invest Dermatol. 2025 May;145(5):1070-1080. doi: 10.1016/j.jid.2024.08.034. Epub 2024 Oct 1.
Targeted systemic immune-modulating drugs to treat atopic dermatitis were highly efficacious in randomized trials. Trials with limited number of subjects leave questions about their safety. We describe a data and analytics structure for the production of timely, high-quality evidence on the comparative safety of recently approved immune-modulating drugs in patients with atopic dermatitis in clinical practice. We established a series of sequential propensity score-balanced cohorts that grow in size with each annual data refresh. Nine health outcomes of interest plus conjunctivitis as a positive tracer outcome were identified. The initial treatment comparison was dupilumab, an IL-4/13 inhibitor, or tralokinumab, an IL-13 inhibitor, versus abrocitinib/upadacitinib, both Jak inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating Jak inhibitors and 2650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well-balanced after propensity score matching. Outpatient infections within 180 days occurred in 18% of Jak1 inhibitor initiators versus 12% of dupilumab/tralokinumab initiators (risk ratio = 1.50, 95% confidence interval = 0.96-2.33), whereas acne risks were 7 versus 3%, respectively (risk ratio = 2.29, 95% confidence interval = 0.96-5.46). This sequential monitoring system will produce essential knowledge on the safety of immune-modulating drugs to treat atopic dermatitis on the basis of its growing study size of patients observed in clinical practice.
在随机试验中，用于治疗特应性皮炎的靶向全身免疫调节药物疗效显著。受试者数量有限的试验使得这些药物的安全性存疑。我们描述了一种数据和分析结构，用于及时生成关于临床实践中特应性皮炎患者近期获批的免疫调节药物比较安全性的高质量证据。我们建立了一系列按顺序排列的倾向评分平衡队列，其规模随着每年的数据更新而扩大。确定了九个感兴趣的健康结局以及作为阳性追踪结局的结膜炎。最初的治疗比较是度普利尤单抗（一种IL-4/13抑制剂）或曲罗芦单抗（一种IL-13抑制剂）与巴瑞替尼/乌帕替尼（两者均为JAK抑制剂）。第一个分析周期（2021年12月至2023年2月）比较了269名开始使用JAK抑制剂的患者和2650名开始使用IL-4/IL-13抑制剂的患者。倾向评分匹配后，患者特征得到了很好的平衡。180天内门诊感染发生率在开始使用JAK1抑制剂的患者中为18%，而在开始使用度普利尤单抗/曲罗芦单抗的患者中为12%（风险比=1.50，95%置信区间=0.96-2.33），而痤疮风险分别为7%和3%（风险比=2.29，95%置信区间=0.96-5.46）。这个连续监测系统将根据其在临床实践中观察到的不断增加的患者研究规模，生成关于治疗特应性皮炎的免疫调节药物安全性的重要知识。
