Leung Donald Y M, Paller Amy S, Zaenglein Andrea L, Tom Wynnis L, Ong Peck Y, Venturanza May E, Kuligowski Michael E, Li Qian, Gong Xiaohua, Lee Mark S
National Jewish Health, Denver, Colorado.
Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Ann Allergy Asthma Immunol. 2023 Apr;130(4):500-507.e3. doi: 10.1016/j.anai.2022.12.033. Epub 2022 Dec 28.
Therapies for children with atopic dermatitis (AD) have safety and tolerability concerns that may limit long-term use. Ruxolitinib cream, a Janus kinase (JAK) inhibitor, is effective and well tolerated in adolescents and adults with AD.
To analyze the safety and tolerability of ruxolitinib cream in pediatric patients. Pharmacokinetics and efficacy were also evaluated in this phase 1 study (NCT03257644).
Patients aged 2 to 17 years with AD (affected body surface area 8%-20%; Investigator's Global Assessment score ≥2) were enrolled stepwise in 6 age-descending, strength-increasing cohorts to apply 0.5%, 0.75%, or 1.5% ruxolitinib cream twice daily for 28 days. Safety, pharmacokinetics, and efficacy were analyzed at baseline, week 2 (day 10), and week 4 (day 29).
Among 71 patients, 44 (62.0%) had a baseline Investigator's Global Assessment score of 3; median (range) body surface area affected at baseline was 12.2% (1.7%-20.4%). Ruxolitinib cream was well tolerated, with 4 patients (5.6%) experiencing treatment-related adverse events (all grades 1/2). No clinically meaningful changes in mean chemistry or hematology values were observed, and no consistent pattern of change in bone biomarkers was detected. Mean plasma ruxolitinib levels within each cohort (range, 23.1-97.9 nM) were well below the half-maximal inhibitory concentration for thrombopoietin phosphorylation of STAT3 (281 nM). All cohorts experienced improvements in exploratory efficacy end points.
Ruxolitinib cream was well tolerated in pediatric patients with AD, with no effect on blood counts or bone biomarkers. Mean plasma concentration was low. Efficacy was consistent with data from previous studies in adolescents and adults.
ClinicalTrials.gov Identifier: NCT03257644.
特应性皮炎（AD）患儿的治疗存在安全性和耐受性问题，这可能会限制其长期使用。鲁索替尼乳膏是一种 Janus 激酶（JAK）抑制剂，在患有 AD 的青少年和成人中有效且耐受性良好。
分析鲁索替尼乳膏在儿科患者中的安全性和耐受性。在这项 1 期研究（NCT03257644）中还评估了药代动力学和疗效。
年龄在 2 至 17 岁的 AD 患者（受累体表面积 8%-20%；研究者整体评估评分≥2）按年龄递减、强度递增的顺序逐步纳入 6 个队列，每天两次涂抹 0.5%、0.75%或 1.5%的鲁索替尼乳膏，持续 28 天。在基线、第 2 周（第 10 天）和第 4 周（第 29 天）分析安全性、药代动力学和疗效。
71 例患者中，44 例（62.0%）基线时研究者整体评估评分为 3 分；基线时受累体表面积的中位数（范围）为 12.2%（1.7%-20.4%）。鲁索替尼乳膏耐受性良好，4 例患者（5.6%）出现与治疗相关的不良事件（均为 1/2 级）。未观察到平均化学或血液学值有临床意义的变化，也未检测到骨生物标志物的一致变化模式。每个队列中的平均血浆鲁索替尼水平（范围为 23.1-97.9 nM）远低于 STAT3 血小板生成素磷酸化的半数最大抑制浓度（281 nM）。所有队列在探索性疗效终点均有改善。
鲁索替尼乳膏在患有 AD 的儿科患者中耐受性良好，对血细胞计数或骨生物标志物无影响。平均血浆浓度较低。疗效与先前在青少年和成人中的研究数据一致。
ClinicalTrials.gov 标识符：NCT03257644。
