两项针对 Ruxolitinib 乳膏治疗白癜风的 3 期、随机、对照临床试验。

Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo.

机构信息

From Tufts Medical Center, Boston (D.R.); Centre Hospitalier Universitaire de Nice and Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, Nice (T.P.), the Office of Mireille Ruer-Mulard, M.D., Martiques (M.R.-M.), the Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164, ImmunoConcept, Université de Bordeaux, Bordeaux (J.S.), and Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, Paris (K.E.) - all in France; Palo Alto Foundation Medical Group, Sunnyvale (A.G.P.), and the Vitiligo and Pigmentation Institute of Southern California, Los Angeles (P.G.) - both in California; the University of Texas Southwestern Medical Center, Dallas (A.G.P., S.R.D.), and Innovative Dermatology, Plano (S.R.D.) - both in Texas; the University of Massachusetts Chan Medical School, Worcester (J.E.H.); Icahn School of Medicine at Mount Sinai, New York (M.L.); Amsterdam University Medical Center, Amsterdam (A.W.); and Incyte, Wilmington, DE (D.K., K.S., K.B.).

出版信息

N Engl J Med. 2022 Oct 20;387(16):1445-1455. doi: 10.1056/NEJMoa2118828.

DOI:10.1056/NEJMoa2118828

PMID:36260792

Abstract

BACKGROUND

Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo.

METHODS

We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale.

RESULTS

A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%).

CONCLUSIONS

In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).

摘要

背景

白癜风是一种慢性自身免疫性疾病，可导致皮肤色素脱失。鲁索替尼（Janus 激酶 1 和 2 的抑制剂）乳膏制剂在涉及白癜风成人的 2 期试验中导致复色。

方法

我们在北美和欧洲进行了两项 3 期、双盲、安慰剂对照试验（TRuE-V1 和 2），纳入年龄在 12 岁及以上、非节段性白癜风且脱色面积占总体表面积的 10%或以下的患者。患者以 2:1 的比例随机分配，每天两次应用 1.5%鲁索替尼乳膏或安慰剂对照，持续 24 周，应用于面部和身体的所有白癜风区域，之后所有患者可在第 52 周前应用 1.5%鲁索替尼乳膏。主要终点是在第 24 周时，与基线相比，面部白癜风面积评分指数（F-VASI；范围为 0 至 3，分数越高表示面部脱色面积越大）下降（改善）至少 75%，或 F-VASI75 应答。有 5 个关键次要终点，包括在白癜风可见性量表上的改善应答。

结果

共有 674 名患者入组，TRuE-V1 组 330 名，TRuE-V2 组 344 名。在 TRuE-V1 中，在第 24 周时 F-VASI75 应答的患者比例，鲁索替尼乳膏组为 29.8%，安慰剂组为 7.4%（相对风险，4.0；95%置信区间[CI]，1.9 至 8.4；P<0.001）。在 TRuE-V2 中，相应的比例分别为 30.9%和 11.4%（相对风险，2.7；95%CI，1.5 至 4.9；P<0.001）。关键次要终点的结果表明鲁索替尼乳膏优于安慰剂对照。在应用鲁索替尼乳膏 52 周的患者中，TRuE-V1 中 54.8%和 TRuE-V2 中 62.3%出现不良反应；最常见的不良反应是用药部位痤疮（分别为 6.3%和 6.6%）、鼻咽炎（分别为 5.4%和 6.1%）和用药部位瘙痒（分别为 5.4%和 5.3%）。

结论

在两项 3 期试验中，与安慰剂相比，鲁索替尼乳膏应用于白癜风病变部位，在 52 周内可导致更多复色，但与用药部位的痤疮和瘙痒有关。需要更大和更长的试验来确定鲁索替尼乳膏在白癜风患者中的疗效和安全性。（由 Incyte 资助；TRuE-V1 和 TRuE-V2 的临床试验.gov 编号，NCT04052425 和 NCT04057573。）