Laboratory of Social Pharmacy and Public Health, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, Polo Ciencias da Saude, 3000-548, Celas, Portugal.
Eur J Clin Pharmacol. 2022 Dec;78(12):1923-1933. doi: 10.1007/s00228-022-03400-4. Epub 2022 Oct 7.
Janus kinase (JAK) inhibitors have been developed to treat moderate to severe atopic dermatitis, but there is little evidence comparing the safety profile of these drugs. The aim of this study is to compare the relative safety of the different systemic JAK inhibitors in atopic dermatitis.
Medline, EMBASE, and clinicaltrials.gov were searched to identify phase 2/3, clinical trials (RCTs) designed to evaluate the efficacy and safety of systemic JAK inhibitors in atopic dermatitis. Outcomes were the risk of any adverse event (AE), serious AEs, AEs leading to treatment discontinuation, any infection, serious infections, herpes zoster infection, and any cardiac or vascular event.
Eighteen RCTs were included. Compared with placebo, baricitinib (odds ratio [OR] 1.25, 95% credible interval [CrI] 1.03-1.55), abrocitinib (OR 1.54, 95% CrI 1.25-1.90), and upadacitinib (OR 1.46, 95% CrI 1.19-1.81) increase the risk of any adverse event. Abrocitinib (OR 1.62, 95% CrI 1.7-2.72), upadacitinib (OR 1.67, 95% CrI 1.19-2.43), and dupilumab (OR 1.69, 95% CrI 1.02-2.79) increase the risk of infections when compared with placebo. Dupilumab has a reduced risk of herpes zoster infection when compared with upadacitinib (OR 0.23; 95% CrI 0.08-0.81) No further statistically significant risk differences between treatments were identified.
The results suggest systemic JAK inhibitors for atopic dermatitis have a similar safety profile. However, as current data present limitations, postmarketing safety evidence will be crucial to draw definitive conclusions regarding the safety of JAK inhibitors.
已开发出 Janus 激酶 (JAK) 抑制剂来治疗中重度特应性皮炎，但关于这些药物安全性的证据很少。本研究旨在比较特应性皮炎中不同全身 JAK 抑制剂的相对安全性。
检索 Medline、EMBASE 和 clinicaltrials.gov，以确定旨在评估全身 JAK 抑制剂在特应性皮炎中的疗效和安全性的 2/3 期临床试验 (RCT)。结果为任何不良事件 (AE)、严重 AE、导致治疗中断的 AE、任何感染、严重感染、带状疱疹感染以及任何心脏或血管事件的风险。
纳入了 18 项 RCT。与安慰剂相比，巴瑞替尼（比值比 [OR] 1.25，95%可信区间 [CrI] 1.03-1.55）、阿布昔替尼（OR 1.54，95% CrI 1.25-1.90）和乌帕替尼（OR 1.46，95% CrI 1.19-1.81）增加了发生任何不良事件的风险。阿布昔替尼（OR 1.62，95% CrI 1.7-2.72）、乌帕替尼（OR 1.67，95% CrI 1.19-2.43）和度普利尤单抗（OR 1.69，95% CrI 1.02-2.79）与安慰剂相比增加了感染的风险。与乌帕替尼相比，度普利尤单抗降低了带状疱疹感染的风险（OR 0.23；95% CrI 0.08-0.81）。未发现治疗之间存在其他具有统计学意义的风险差异。
结果表明，特应性皮炎的全身 JAK 抑制剂具有相似的安全性。然而，由于目前的数据存在局限性，上市后安全性证据对于确定 JAK 抑制剂的安全性至关重要。
