Departments of Dermatology and Pediatrics, University of California San Diego, San Diego, CA, USA.
Rady Children's Hospital, 3020 Children's Way, Mail Code 5092, San Diego, CA, 92123, USA.
Am J Clin Dermatol. 2024 Jul;25(4):669-683. doi: 10.1007/s40257-024-00855-2. Epub 2024 May 2.
Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2).
To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12-17 years from pooled phase 3 study data.
Patients [≥ 12 years old with AD for ≥ 2 years, Investigator's Global Assessment score (IGA) 2/3, and 3-20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study.
Of 1249 randomized patients, 245 (19.6%) were aged 12-17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [- 0.9 (1.9) versus -0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events.
Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated.
ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018).
特应性皮炎（AD）是一种高度瘙痒、炎症性皮肤疾病，全球约有 7%的青少年受其影响。在两项 3 期研究（TRuE-AD1/TRuE-AD2）中，一种 JAK1/JAK2 抑制剂鲁索利替尼的局部制剂在青少年/成年人中表现出安全性和疗效。
描述在汇总的 3 期研究数据中，12-17 岁青少年患者应用 1.5%鲁索利替尼乳膏与安慰剂相比的安全性和疗效，以及鲁索利替尼乳膏的长期疾病控制情况。
患者（年龄≥ 12 岁，AD 病史≥ 2 年，研究者整体评估[IGA]评分 2/3，基线时体表面积[BSA]受累 3%-20%）按 2:2:1 的比例随机分为鲁索利替尼乳膏（0.75%/1.5%）或安慰剂组，连续使用 8 周，随后进入长达 52 周的长期安全性（LTS）期，按需使用。最初应用安慰剂的患者按 1:1 的比例重新随机分为 0.75%/1.5%鲁索利替尼乳膏组。第 8 周的疗效评估指标包括 IGA 治疗成功（IGA-TS，即与基线相比评分 0/1，改善≥ 2 级）、湿疹面积和严重程度指数（EASI-75）改善≥ 75%和瘙痒数字评分量表（NRS4）改善≥ 4 分。LTS 期间疾病控制的评估指标包括 IGA 评分 0（清除）或 1（几乎清除）和 BSA 受累百分比。整个研究过程中评估安全性。
在 1249 名随机患者中，245 名（19.6%）为 12-17 岁的青少年。其中，45 名患者随机分配至安慰剂组，92 名患者随机分配至 1.5%鲁索利替尼乳膏组。共有 104/137 名（75.9%）患者在 LTS 期间继续应用 1.5%鲁索利替尼乳膏[82/92（89.1%）继续应用 1.5%鲁索利替尼乳膏；45 名患者中的 22 名（48.9%）被重新分配至 1.5%鲁索利替尼乳膏组]，其中 83/104 名（79.8%）患者完成了 LTS 期。第 8 周时，与安慰剂相比，应用 1.5%鲁索利替尼乳膏的患者中达到 IGA-TS（50.6%与 14.0%）、EASI-75（60.9%与 34.9%）和 NRS4（52.1%与 17.4%）的患者比例显著更高（P = 0.009）。与安慰剂相比，应用 1.5%鲁索利替尼乳膏的患者从第 2 天开始，瘙痒 NRS 评分的平均（SD）下降幅度显著更大[-0.9（1.9）与-0.2（1.4）；P = 0.03]。在 LTS 期间，第 12 周/第 52 周时的稳态下鲁索利替尼血浆浓度的平均值（SD）分别为 27.2（55.7）/15.5（31.5）nm。继续应用 1.5%鲁索利替尼乳膏，IGA 评分 0 或 1 的患者比例维持或进一步增加；平均受累 BSA 通常较低（< 3%，即轻度疾病）。至 52 周时，1.5%鲁索利替尼乳膏组的青少年患者中有 1.8%在任何时候出现应用部位反应；无患者发生严重不良事件。无严重感染、恶性肿瘤、重大不良心血管事件或血栓栓塞事件。
在 AD 青少年患者亚组中，与整体研究人群观察到的情况相当，应用 1.5%鲁索利替尼乳膏可产生有意义的抗炎和止痒效果；长期按需使用可维持疾病控制且具有良好的耐受性。
ClinicalTrials.gov 标识符 NCT03745638（于 2018 年 11 月 19 日注册）和 NCT03745651（于 2018 年 11 月 19 日注册）。
