背景:需要具有可接受安全性的全身性特应性皮炎治疗。
目的:评价口服Janus激酶抑制剂upadacitinib联合外用糖皮质激素(TCSs)治疗特应性皮炎的安全性。
方法:在此阶段3,双盲研究(上升),患有中度至重度特应性皮炎的日本患者(12-75岁)以1:1:1的比例随机接受15mgupadacitinib+TCS,30毫克upadacitinib+TCS,或安慰剂+TCS(以1:1的比例重新随机化,在第16周时接受15或30mgupadacitinib+TCS)。对不良事件和实验室数据进行安全性评估。
结果:在272名接受治疗的患者中,在第24周,15-和30-mgupadacitinib+TCS的严重不良事件发生率相似(15mg,56%;30mg,64%),但高于安慰剂+TCS(42%)。使用upadacitinib+TCS(15mg,13.2%;30mg,19.8%)高于安慰剂+TCS(5.6%)。此外,带状疱疹感染(4.4%vs0%),贫血(1.1%vs0%),中性粒细胞减少症(4.4%vs1.1%),30mgupadacitinib+TCS比15mgupadacitinib+TCS更常见肌酸磷酸激酶升高(2.2%vs1.1%);安慰剂+TCS均未报告这些事件.无血栓栓塞事件,恶性肿瘤,胃肠道穿孔,活动性肺结核,或死亡发生。
结论:这些限制包括样本量小,观察期短以及结果在日本人群以外的不可推广性。
结论:结果与以前的报告基本一致;没有发现新的安全风险。
BACKGROUND: Systemic atopic dermatitis treatments that have acceptable safety are needed.
OBJECTIVE: To evaluate the safety of the oral Janus kinase inhibitor upadacitinib in combination with topical corticosteroids (TCSs) for the treatment of atopic dermatitis.
METHODS: In this phase 3, double-blind study (Rising Up), Japanese patients (12-75 years) with moderate-to-severe atopic dermatitis were randomized in a 1:1:1 ratio to receive 15 mg of upadacitinib + TCS, 30 mg of upadacitinib + TCS, or a placebo + TCS (rerandomized in a 1:1 ratio to receive either 15 or 30 mg of upadacitinib + TCS at week 16). Adverse events and laboratory data were assessed for safety.
RESULTS: In 272 treated patients, the serious adverse event rates were similar for 15- and 30-mg upadacitinib + TCS at week 24 (15 mg, 56%; 30 mg, 64%) but greater than those for placebo + TCS (42%). Acne (all mild or moderate; none leading to discontinuation) occurred more frequently with upadacitinib + TCS (15 mg, 13.2%; 30 mg, 19.8%) than with placebo + TCS (5.6%). Furthermore, herpes zoster infection (4.4% vs 0%), anemia (1.1% vs 0%), neutropenia (4.4% vs 1.1%), and creatine phosphokinase elevations (2.2% vs 1.1%) occurred more frequently with 30-mg upadacitinib + TCS than with 15-mg upadacitinib + TCS; none of these events were reported with placebo + TCS. No thromboembolic events, malignancies, gastrointestinal perforations, active tuberculosis, or deaths occurred.
CONCLUSIONS: The limitations included a small sample size and short observation period as well as nongeneralizability of the results beyond Japanese populations.
CONCLUSIONS: The results were generally consistent with those of previous reports; no new safety risks were detected.