■抑制Janus激酶(JAK)是治疗白癜风的一种有希望的方法。我们旨在评估upadacitinib的疗效和安全性,一种口服选择性JAK抑制剂,在成人非节段白癜风中。
■这是第二阶段,多中心,随机化,双盲,安慰剂对照,在美国33个临床中心完成的剂量范围研究,加拿大,法国,和日本。符合条件的患者年龄为18-65岁,患有非节段白癜风,面部白癜风面积评分指数(F-VASI)≥0.5,总白癜风面积评分指数(T-VASI)≥5。患者被随机分配(2:2:2:1:1)使用交互式反应技术接受upadacitinib6mg(UPA6),upadacitinib11mg(UPA11),upadacitinib22mg(UPA22),或安慰剂(PBO;在第2期预先分配到UPA11或UPA22),每天一次,持续24周(第1期)。第24-52周(第2期),随机分配到upadacitinib的患者继续他们的治疗,接受PBO的患者以盲法方式切换至预设的upadacitinib剂量.主要终点是第24周时F-VASI相对于基线的百分比变化。在意向治疗人群中分析疗效,在接受至少一剂研究药物的所有随机分配的患者中进行安全性检查.这项研究在ClinicalTrials.gov注册,编号NCT04927975。
■在2021年6月16日至2022年6月27日之间,185名患者(包括115名女性[62%]和70名男性[38%])被随机分配到UPA6(n=49),UPA11(n=47),UPA22(n=43),或PBO(n=46)。在第24周,UPA6的F-VASI与PBO的基线变化百分比的LS均值差异为-7.60(95%CI-22.18至6.97;p=0.3037),UPA11的-21.27(95%CI-36.02至-6.52;p=0.0051),UPA22的-19.60(95%CI-35.04至-4.16;p=0.0132)。与PBO相比,T-VASI基线变化百分比的LS平均差为-7.45(95%CI-16.86至1.96;p=0.1198),UPA6为-10.84(95%CI-20.37至-1.32;p=0.0259),UPA11为-14.27(95%CI-24.24至-4.30;p=0.0053)。正在进行的upadacitinib治疗随着时间的推移引起持续的皮肤色素沉着,直到第52周没有达到平台期。UPA22组的研究药物停药和严重治疗引起的不良事件(TEAE)的发生率高于UPA11和UPA6组。八个严肃的团队,包括1例不明原因死亡和1例浸润性小叶乳腺癌,在52周内报告;研究者认为只有2例严重TEAE(冠状动脉粥样硬化[UPA6(n=1)]和非致死性缺血性卒中[UPA11(n=1)])具有与研究药物相关的合理可能性.UPA11组中的一例乳腺癌被认为与研究药物无关,对UPA22组中1例原因不明的死亡进行了审查和裁定,认为与研究药物无关.最常见的TEAE是COVID-19,头痛,痤疮,和疲劳。没有观察到新的安全信号。
Upadacitinib单药治疗可导致面部和全身白癜风病变的大量色素沉着,可能为患有广泛非节段白癜风的成人提供有效的治疗选择。基于这些发现,在一项正在进行的3期随机对照试验中,正在对患有非节段白癜风的成人和青少年患者进行upadacitinib15mg的研究.
■AbbVieInc.
UNASSIGNED: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of
upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo.
UNASSIGNED: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6),
upadacitinib 11 mg (UPA11),
upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to
upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned
upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975.
UNASSIGNED: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with
upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed.
UNASSIGNED: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial.
UNASSIGNED: AbbVie Inc.