Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
Department of Pediatrics, Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass.
J Allergy Clin Immunol. 2024 Nov;154(5):1195-1203.e3. doi: 10.1016/j.jaci.2024.07.019. Epub 2024 Aug 7.
Systemic Janus kinase inhibitors (JAKi) and dupilumab both have emerged as promising therapeutics for atopic dermatitis (AD). Dupilumab has a favorable safety profile, but oral JAKi therapy has been established in other diseases that carry potential comorbid susceptibilities that influence safety.
We sought to provide real-world evidence of the comparative safety of oral JAKi versus dupilumab in patients with AD.
The study used observational data from multiple healthcare organizations in the US. Patients with AD treated with either oral JAKi (upadacitinib, abrocitinib, and baricitinib) or dupilumab were enrolled. The 2 treatment groups were propensity score matched 1:1 on the basis of demographics, comorbidities, and prior medications. Safety outcomes within 2 years after the initiation of medications were measured by hazard ratios (HRs) with 95% confidence intervals (CIs).
A total of 14,716 patients were included, with 942 patients treated with oral JAKi and 13,774 with dupilumab. The 2 treatment groups respectively included 938 patients after matching. Treatment with oral JAKi was not associated with increased risks of mortality, malignancies, major adverse cardiovascular events, venous thromboembolism, renal events, or serious gastrointestinal events. However, patients receiving oral JAKi showed significantly higher risks of skin and subcutaneous tissue infection (HR = 1.35, 95% CI = 1.07-1.69), herpes infection (herpes simplex, HR = 1.64, 95% CI = 1.03-2.61; herpes zoster, HR = 2.51, 95% CI = 1.14-5.52), acne (HR = 2.09, 95% CI = 1.54-2.84), cytopenia (anemia, HR = 1.83, 95% CI = 1.39-2.41; neutropenia, HR = 4.02, 95% CI = 1.91-8.47; thrombocytopenia, HR = 1.76, 95% CI = 1.08-2.89), and hyperlipidemia (HR = 1.45, 95% CI = 1.09-1.92); the risk of ophthalmic complications was higher in those receiving dupilumab (HR = 1.49, 95% CI = 1.03-2.17).
Oral JAKi did not exhibit concerning safety issues in treating patients with AD but increased the risk of infections and abnormalities in laboratory findings. Long-term follow-up data are required to validate these results.
全身性 Janus 激酶抑制剂（JAKi）和度普利尤单抗均已成为特应性皮炎（AD）有前途的治疗方法。度普利尤单抗具有良好的安全性，但是其他疾病中已经确立了口服 JAKi 治疗方法，这些疾病存在潜在的合并症易感性，会影响安全性。
我们旨在提供口服 JAKi 与度普利尤单抗在 AD 患者中比较安全性的真实世界证据。
该研究使用了来自美国多个医疗机构的观察性数据。纳入接受口服 JAKi（乌帕替尼、阿布昔替尼和巴瑞替尼）或度普利尤单抗治疗的 AD 患者。基于人口统计学、合并症和既往药物治疗情况，将这 2 个治疗组进行 1:1 倾向评分匹配。在药物治疗开始后 2 年内测量安全性结局，采用风险比（HR）及其 95%置信区间（CI）进行评估。
共纳入 14716 例患者，其中 942 例患者接受口服 JAKi 治疗，13774 例患者接受度普利尤单抗治疗。匹配后，两组分别纳入 938 例患者。接受口服 JAKi 治疗与死亡率、恶性肿瘤、主要不良心血管事件、静脉血栓栓塞、肾脏事件或严重胃肠道事件的风险增加无关。然而，接受口服 JAKi 治疗的患者皮肤和皮下组织感染（HR=1.35，95%CI=1.07-1.69）、疱疹感染（单纯疱疹，HR=1.64，95%CI=1.03-2.61；带状疱疹，HR=2.51，95%CI=1.14-5.52）、痤疮（HR=2.09，95%CI=1.54-2.84）、细胞减少症（贫血，HR=1.83，95%CI=1.39-2.41；中性粒细胞减少症，HR=4.02，95%CI=1.91-8.47；血小板减少症，HR=1.76，95%CI=1.08-2.89）和血脂异常（HR=1.45，95%CI=1.09-1.92）的风险更高；接受度普利尤单抗治疗的患者发生眼部并发症的风险更高（HR=1.49，95%CI=1.03-2.17）。
口服 JAKi 治疗 AD 患者未显示出令人担忧的安全性问题，但会增加感染和实验室检查结果异常的风险。需要进行长期随访数据来验证这些结果。
