美国塔夫茨医疗中心David Rosmarin团队研究了鲁索替尼乳膏治疗白癜风的效果。2020年7月11日，该研究发表在《柳叶刀》杂志上。

白癜风是一种慢性自身免疫性疾病，会导致皮肤脱色并降低生活质量。目前尚无批准的治疗白癜风的方法，非标签疗法疗效有限，急需改进。研究组调查了鲁索替尼乳膏对白癜风患者的治疗潜力，并报告了长达52周的双盲治疗的疗效和安全性结果。

研究组在美国18个州的26家医院和医疗中心对成年白癜风患者进行了一项多中心、随机、双盲2期研究。2017年6月7日至2018年3月21日，研究组招募了157例白癜风患者，面部脱色0.5%以上，非面部脱色3%以上，平均年龄48.3岁，男性占46％，女性占54％。

将其按1:1:1:1:1随机分组，其中31名接受每日一次0.15%的鲁索替尼乳膏，31名接受每日一次0.5%，30名接受每日一次1.5%，33名接受每日两次1.5%，32名接受安慰剂治疗。主要终点为第24周时面部白癜风面积评分指数（F-VASI50）与基线相比改善50%以上患者的比例。若对照组患者在第24周时改善未达到25%，则将其随机分到除每日一次0.15%组之后的其他三组，并随访至52周。

接受每日两次1.5%鲁索替尼乳膏治疗的患者和接受每日一次1.5%鲁索替尼乳膏治疗的患者，在第24周时达到F-VASI50的患者数分别占45%和50%，显著高于对照组（3%）。共发生4例严重的治疗紧急事件，其中每日两次1.5％鲁索替尼乳膏组中有一名患者发生硬膜下血肿；每日一次1.5％组中有一名患者癫痫发作；每日一次0.5％组中有一名患者发生冠状动脉闭塞，一名患者发生食管贲门失弛缓症，所有这些均与研究治疗无关。

在使用鲁索替尼乳膏的患者中，用药部位瘙痒是与治疗有关的最常见不良事件，其中每日两次1.5%组的发生率为3%，每日1次1.5%组为10%，每日1次0.5%组为10%，每日1次0.15%组为19%，对照组为9%。在接受鲁索替尼乳膏治疗的125例患者中有13例（10％）发生治疗相关的痤疮，而对照组中有1例（3％）。所有与治疗相关的不良事件均为轻中度，各治疗组间相差不大。

总之，鲁索替尼乳膏治疗白癜风52周后，可有效恢复色素沉着，且所有剂量的耐受性良好，表明鲁索替尼乳膏可作为白癜风患者的有效治疗选择。

附：英文原文

Title: Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial

Author: David Rosmarin, Amit G Pandya, Mark Lebwohl, Pearl Grimes, Iltefat Hamzavi, Alice B Gottlieb, Kathleen Butler, Fiona Kuo, Kang Sun, Tao Ji, Michael D Howell, John E Harris

Issue&Volume: 2020/07/11

Abstract: Background

Vitiligo is a chronic autoimmune disease resulting in skin depigmentation and reduced quality of life. There is no approved treatment for vitiligo repigmentation and current off-label therapies have limited efficacy, emphasising the need for improved treatment options. We investigated the therapeutic potential of ruxolitinib cream in patients with vitiligo and report the efficacy and safety results up to 52 weeks of double-blind treatment.

Methods

We did a multicentre, randomised, double-blind, phase 2 study for adult patients with vitiligo in 26 US hospitals and medical centres in 18 states. Patients with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA were randomly assigned (1:1:1:1:1) by use of an interactive response technology system to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle (control group) twice daily on lesions constituting 20% or less of their total BSA for 24 weeks. Patients in the control group in addition to patients in the 0·15% once daily group who did not show a 25% or higher improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI) at week 24 were re-randomised to one of three higher ruxolitinib cream doses (0·5% once daily, 1·5% once daily, 1·5% twice daily). Patients in the 0·5% once daily, 1·5% once daily, or 1·5% twice daily groups remained at their original dose up to week 52. Patients, investigators, and the study sponsor (except members of the interim analysis and primary endpoint analysis data monitoring teams) remained masked to treatment assignment throughout the study. The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in F-VASI (F-VASI50) at week 24, assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03099304.

Findings

Between June 7, 2017, and March 21, 2018, 205 patients were screened for eligibility, 48 were excluded and 157 patients (mean age, 48·3 years [SD 12·9]; 73 [46%] male and 84 [54%] female) were randomly assigned to either an intervention group or the control group. 32 (20%) of 157 were assigned to the control group, 31 (20%) to the 0·15% once daily group, 31 (20%) to the 0·5% once daily group, 30 (19%) to the 1·5% once daily group, and 33 (21%) to the 1·5% twice daily group. F-VASI50 at week 24 was reached by significantly more patients given ruxolitinib cream at 1·5% twice daily (15 [45%] of 33) and 1·5% once daily (15 [50%] of 30) than were treated with vehicle (one [3%] of 32). Four patients had serious treatment-emergent adverse events (one patient in the 1·5% twice daily group developed subdural haematoma; one patient in the 1·5% once daily group had a seizure; one patient in the 0·5% once daily group had coronary artery occlusion; and one patient in the 0·5% once daily group had oesophageal achalasia), all of which were unrelated to study treatment. Application site pruritus was the most common treatment-related adverse event among patients given ruxolitinib cream (one [3%] of 33 in the 1·5% twice daily group; three [10%] of 30 in the 1·5% once daily group; three [10%] of 31 in the 0·5% once daily group; and six [19%] of 31 in the 0·15% once daily group)with three [9%] of 32 patients showing application site pruritis in the control group. Acne was noted as a treatment-related adverse event in 13 (10%) of 125 patients who received ruxolitinib cream and one (3%) of 32 patients who received vehicle cream. All treatment-related adverse events were mild or moderate in severity and similar across treatment groups.

Interpretation

Treatment with ruxolitinib cream was associated with substantial repigmentation of vitiligo lesions up to 52 weeks of treatment, and all doses were well tolerated. These data suggest that ruxolitinib cream might be an effective treatment option for patients with vitiligo.

DOI: 10.1016/S0140-6736(20)30609-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30609-7/fulltext