Maria C Schneeweiss, Robert J Glynn, Richard Wyss, Priyanka Anand, Yinzhu Jin, Joan Landon, Arash Mostaghimi, Joseph F Merola, Jonathan I Silverberg, David M Rosmarin, Robert Sidbury, Sebastian Schneeweiss
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The initial treatment comparison was dupilumab, an interleukin-4/13 inhibitor, or tralokinumab, an interleukin-13 inhibitor, versus abrocitinib/upadacitinib, both JAK inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating JAK inhibitors and 2,650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well balanced after PS-matching. Outpatient infections within 180 days occurred in 18% of JAK-1 inhibitor initiators versus 12% of dupilumab/ tralokinumab initiators (RR=1.50; 0.96 to 2.33) whereas acne risks were 7% vs. 3%, respectively (RR=2.29, 0.96 to 5.46). 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引用次数: 0
摘要
治疗特应性皮炎(AD)的靶向性全身免疫调节药物(IMDs)在随机试验中疗效显著。但受试者人数有限的试验对其安全性提出了质疑。我们介绍了一种数据和分析结构,用于及时提供高质量的证据,说明最近批准的 IMDs 在临床实践中对 AD 患者的安全性比较。我们建立了一系列连续的倾向得分(PS)平衡队列,其规模随着每年数据的更新而扩大。我们确定了九种相关的健康结果以及作为阳性示踪结果的结膜炎。最初的治疗比较是白细胞介素-4/13抑制剂杜必鲁单抗或白细胞介素-13抑制剂曲妥珠单抗与阿罗西替尼/乌帕他替尼(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。经过 PS 匹配后,患者特征非常均衡。JAK-1抑制剂启动者在180天内发生门诊感染的比例为18%,而杜比鲁单抗/曲妥珠单抗启动者为12%(RR=1.50;0.96-2.33),而痤疮风险分别为7%和3%(RR=2.29,0.96-5.46)。基于对临床实践中观察到的患者进行的研究规模不断扩大,这一连续监测系统将为IMDs治疗AD的安全性提供重要知识。
A scalable approach to assess the safety of recently marketed systemic treatments for atopic dermatitis in clinical practice.
Targeted systemic immune-modulating drugs (IMDs) to treat atopic dermatitis (AD) 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 IMDs in patients with AD in clinical practice. We established a series of sequential propensity score (PS)-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 interleukin-4/13 inhibitor, or tralokinumab, an interleukin-13 inhibitor, versus abrocitinib/upadacitinib, both JAK inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating JAK inhibitors and 2,650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well balanced after PS-matching. Outpatient infections within 180 days occurred in 18% of JAK-1 inhibitor initiators versus 12% of dupilumab/ tralokinumab initiators (RR=1.50; 0.96 to 2.33) whereas acne risks were 7% vs. 3%, respectively (RR=2.29, 0.96 to 5.46). This sequential monitoring system will produce essential knowledge on the safety of IMDs to treat AD based on its growing study size of patients observed in clinical practice.