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P96: Safety and efficacy of ruxolitinib cream for the treatment of vitiligo: 156-week data from a phase II study
First published: 05 July 2022 https://doi.org/10.1111/bjd.21218
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John E. Harris,1 Amit G. Pandya,2,3 Mark Lebwohl,4 Iltefat H. Hamzavi,5 Pearl Grimes,6 Alice B. Gottlieb,4 Howard L. Sofen,7 Angela Y. Moore,8,9 Mingyue Wang,10 Deanna Kornacki,10 Kathleen Butler10 and David Rosmarin11
1University of Massachusetts Medical School, Worcester, MA, USA; 2Palo Alto Foundation Medical Group, Mountain View, CA, USA; 3University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Henry Ford Medical Center, Detroit, MI, USA; 6The Vitiligo & Pigmentation Institute of Southern California, Los Angeles, CA, USA; 7David Geffen UCLA School of Medicine, Los Angeles, CA, USA; 8Arlington Research Center, Arlington, VA, USA; 9Baylor University Medical Center, Dallas, TX, USA; 10Incyte Corporation, Wilmington, NC, USA; and 11Tufts Medical Center, Boston, MA, USA
Vitiligo is a chronic autoimmune disease characterized by the destruction of melanocytes, resulting in pale or white patches of skin. Disease pathogenesis is largely regulated by interferon-γ, which activates signalling pathways regulated by Janus kinase (JAK) 1 and JAK2. In a phase II, dose-ranging, randomized study (NCT03099304), ruxolitinib (JAK1/JAK2 inhibitor) cream demonstrated significant repigmentation at 24 and 52 weeks in adult patients with vitiligo [n = 157; depigmentation ≥ 0.5% of body surface area (BSA) on the face and ≥ 3% of BSA on nonfacial areas] when applied to ≤ 20% total BSA. Here, safety and efficacy data at 156 weeks are reported. Of 79 patients who applied 0.5% ruxolitinib cream once daily (q24h), 1.5% q24h or 1.5% twice daily (q12h) and completed the 52-week randomized period, 77 continued to apply 1.5% ruxolitinib cream q12h in the open-label period for another 104 weeks. Thirty-six patients (47%) discontinued open-label treatment, most commonly because of withdrawal by the patient (n = 25). Treatment-emergent adverse events (TEAEs) were reported in 44 patients (57%) during the 104-week open-label period; two patients (2.6%) discontinued treatment due to a TEAE. Seven patients (9%) had a TEAE considered related to treatment (TRAE), all of which were grade 1/2. Among patients initially randomized to apply ruxolitinib 1.5% cream q12h (n = 33), 26 (79%) reported TEAEs over the 156-week study period; 11 patients (33.3%) experienced TRAEs, all of which were grade 1 (n = 10) or 2 (n = 1). Regardless of dose at initial randomization, no accumulation of AEs or clinically relevant changes in mean haemoglobin or platelet levels were observed over the 156-week treatment period. Among all evaluable patients with a week 156 study visit (n = 25), ≥ 50%, ≥ 75% and ≥ 90% improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI50, F-VASI75 and F-VASI90, respectively) was achieved by 92%, 68.0%, and 48.0% of patients, respectively; 56% achieved clear (i.e. no signs of vitiligo) or almost-clear skin (i.e. only specks of depigmentation present) in the facial assessment of the Physician’s Global Vitiligo Assessment (F-PhGVA 0/1). At least 50% improvement in total body VASI (T-VASI50) was achieved by 60% of patients at week 156. Among patients initially randomized to ruxolitinib 1.5% cream q12h (n = 33) with a week 156 study visit (n = 9), F-VASI50, F-VASI75, F-VASI90 and T-VASI50 were achieved by 100%, 88.9%, 66.7% and 77.8% of patients, respectively; F-PhGVA 0/1 was achieved by 88.9% of patients at week 156. In summary, treatment with ruxolitinib cream was well tolerated over a 3-year period and resulted in substantial and clinically meaningful repigmentation of vitiligo lesions on both the face and total body.P96： 鲁索利替尼乳膏治疗白癜风的安全性和有效性：来自II期研究的156周数据
首次发布：05 七月 2022
https://doi.org/10.1111/bjd.21218
约翰•哈里斯，1阿米特·潘迪亚，2,3马克·勒布沃尔，4伊尔特法特•5珍珠污垢，6爱丽丝•戈特利布，4霍华德•索芬，7安吉拉•摩尔，8,9王明月，10迪安娜•科尔纳基，10凯瑟琳·巴特勒10和大卫·罗斯马林11
1马萨诸塞大学医学院，伍斯特，马萨诸塞州，美国; 2帕洛阿尔托基金会医疗集团，山景城，加利福尼亚州，美国; 3德克萨斯大学西南医学中心，达拉斯，德克萨斯州，美国; 4西奈山伊坎医学院，纽约州纽约市，美国; 5亨利福特医疗中心，底特律，密歇根州，美国; 6南加州白癜风和色素沉着研究所，洛杉矶，加利福尼亚州，美国; 7David Geffen UCLA医学院， 洛杉矶， CA， 美国; 8阿灵顿研究中心，弗吉尼亚州阿灵顿，美国; 9贝勒大学医学中心，达拉斯，德克萨斯州，美国; 10Incyte Corporation， Wilmington， NC， USA;和 11塔夫茨医疗中心，波士顿，马萨诸塞州，美国
白癜风是一种慢性自身免疫性疾病，其特征在于黑素细胞的破坏，导致皮肤苍白或白色斑块。疾病发病机制主要由干扰素γ调节，干扰素激活由Janus激酶（JAK）1和JAK2调节的信号通路。在一项 II 期临床试验 （NCT03099304） 中，ruxolitinib（JAK1/JAK2 抑制剂）乳膏显示，当 ≤应用于 20% 的总 BSA 时，成人白癜风患者在 24 周和 52 周时出现显著色素沉着[n = 157;面部色素脱失≥ 0.5% 的体表面积 （BSA），非面部 BSA ≥ 3%。在这里，报告了156周的安全性和有效性数据。在79例患者中，施用0.5%鲁索利替尼乳膏，每日一次（q24h），1.5%q24h或1.5%，每日两次（q12h）并完成52周随机期，77例继续在开放标签期使用1.5%鲁索利替尼乳膏q12h，再持续104周。36名患者（47%）停止开放标签治疗，最常见的原因是患者停药（n = 25）。在104周开放标签期间，44名患者（57%）报告了治疗紧急不良事件（TEAEs）;两名患者（2.6%）因TEAE而停止治疗。7名患者（9%）的TEAE被认为与治疗有关（TRAE），所有这些都是1/2级。在最初随机应用鲁索利替尼1.5%乳膏q12h（n = 33）的患者中，26（79%）在156周的研究期间报告了TEAEs;11名患者（33.3%）经历了TRAE，所有这些都是1级（n = 10）或2级（n = 1）。无论初始随机化时的剂量如何，在156周的治疗期间，均未观察到AE的积累或平均血红蛋白或血小板水平的临床相关变化。在所有接受为期156周的研究访问（n = 25）的可评估患者中，面部白癜风区域评分指数（分别为F-VASI50，F-VASI75和F-VASI90）分别比基线提高了92%，68.0%和48.0%≥50%，≥75%和≥90%;56%的人在医生全球白癜风评估（F-PhGVA 0/1）的面部评估中达到透明（即没有白癜风的迹象）或几乎透明的皮肤（即仅存在色素沉着斑点）。60% 的患者在第 156 周时全身 VASI （T-VASI50） 至少改善了 50%。在最初随机分配到鲁索利替尼1.5%乳膏q12h（n = 33）并进行为期156次研究访问（n = 9）的患者中，F-VASI50，F-VASI75，F-VASI90和T-VASI50分别达到100%，88.9%，66.7%和77.8%;88.9%的患者在第156周达到F-PhGVA 0/1。总之，用鲁索利替尼乳膏治疗在3年内具有良好的耐受性，并导致面部和全身白癜风病变的大量和临床意义的再治疗 |
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发表于 2022-7-10 11:41:22
