Gooderham Melinda J, Hong H Chih-Ho, Wang Di, Hooper Becky, Hughes-Martin Avery, Cameron Heather, Pastor Laura, Pepper Alicia, Wu Ping, Mojebi Ali, Wong Grace, Marino Rafael, Dion Marie-Lise, Larbi Mehdi
SKiN Centre for Dermatology, 775 Monaghan Road, Peterborough, ON, K9J 5K2, Canada.
Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
Dermatol Ther (Heidelb). 2025 Sep 4. doi: 10.1007/s13555-025-01503-1.
Atopic dermatitis (AD) is a chronic, highly pruritic, relapsing inflammatory disease associated with high quality-of-life burden. Topical 1.5% ruxolitinib cream is a selective Janus kinase (JAK)1/JAK2 inhibitor that is well tolerated and effective in improving itch and lesion clearance in patients ≥ 12 years old. This analysis estimates comparative efficacy for 1.5% ruxolitinib cream relative to systemic therapies for treatment of patients ≥ 12 years with AD.
A systematic literature review (SLR) identified randomized controlled trials evaluating 1.5% ruxolitinib cream, oral JAK inhibitors, monoclonal antibodies, phosphodiesterase 4 inhibitors, and systemic immunosuppressants. A feasibility assessment evaluated whether indirect treatment comparison (ITC) was appropriate and determined appropriate ITC methods. This network meta-analysis (NMA) assessed the comparative efficacy of 1.5% ruxolitinib cream against systemic therapies in a "systemic-eligible moderate AD" subgroup defined as ≥ 12 years old and eligible for topical and systemic therapies (Investigator's Global Assessment [IGA] = 3, Eczema Area and Severity Index [EASI] ≥ 16, and body surface area ≥ 10%); an ITC with the full study populations was not feasible. A frequentist framework using a penalized likelihood NMA included outcomes of IGA 0/1 with at least a 2-point improvement from baseline, EASI-75, and Itch Numerical Rating Scale 4 (NRS4).
The SLR identified 25 studies, of which 12 reported outcomes for the relevant subgroup for four interventions: 1.5% ruxolitinib cream, dupilumab 300 mg, upadacitinib (15 mg, 30 mg), and abrocitinib (100 mg, 200 mg), which were compared against placebo or placebo + topical corticosteroids. There were no statistically significant differences between active comparators for IGA 0/1, EASI-75, and Itch NRS4, although point estimates numerically favored 1.5% ruxolitinib cream for IGA 0/1 and EASI‑75.
For patients with moderate AD who are eligible for systemic therapies, 1.5% ruxolitinib cream might provide disease control comparable to systemic treatments, such as dupilumab, regarding IGA 0/1, EASI-75, and Itch NRS4.
特应性皮炎（AD）是一种慢性、高度瘙痒、复发性炎症性疾病，给患者的生活质量带来沉重负担。外用1.5%芦可替尼乳膏是一种选择性Janus激酶（JAK）1/JAK2抑制剂，耐受性良好，对改善12岁及以上患者的瘙痒和皮损清除有效。本分析评估了1.5%芦可替尼乳膏相对于全身治疗药物治疗12岁及以上AD患者的相对疗效。
一项系统文献综述（SLR）确定了评估1.5%芦可替尼乳膏、口服JAK抑制剂、单克隆抗体、磷酸二酯酶4抑制剂和全身免疫抑制剂的随机对照试验。一项可行性评估评估了间接治疗比较（ITC）是否合适，并确定了合适的ITC方法。这项网络荟萃分析（NMA）评估了1.5%芦可替尼乳膏在一个定义为12岁及以上且适合局部和全身治疗（研究者整体评估[IGA]=3、湿疹面积和严重程度指数[EASI]≥16且体表面积≥10%）的“全身治疗适用的中度AD”亚组中相对于全身治疗药物的比较疗效；对整个研究人群进行ITC不可行。使用惩罚似然NMA的频率论框架纳入了IGA 0/1（相对于基线至少改善2分）、EASI-75和瘙痒数字评定量表4（NRS4）的结果。
SLR确定了25项研究，其中12项报告了四种干预措施相关亚组的结果：1.5%芦可替尼乳膏、度普利尤单抗300 mg、乌帕替尼（15 mg、30 mg）和阿布昔替尼（100 mg、200 mg），这些药物与安慰剂或安慰剂+外用糖皮质激素进行了比较。对于IGA 0/1、EASI-75和瘙痒NRS4，活性对照药物之间没有统计学显著差异，尽管IGA 0/1和EASI-75的点估计值在数值上更倾向于1.5%芦可替尼乳膏。
对于有全身治疗适应证的中度AD患者，就IGA 0/1、EASI-75和瘙痒NRS4而言，1.5%芦可替尼乳膏可能提供与度普利尤单抗等全身治疗相当的疾病控制效果。
