大麻素受体 2 激动剂利纳巴斯治疗伴有难治性皮肤疾病的皮肌炎患者的安全性和疗效：一项随机临床试验。
Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: A Randomized Clinical Trial.
机构信息
Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, U.S. Department of Veterans Affairs, Philadelphia, Pennsylvania, USA; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, U.S. Department of Veterans Affairs, Philadelphia, Pennsylvania, USA; Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
出版信息
J Invest Dermatol. 2022 Oct;142(10):2651-2659.e1. doi: 10.1016/j.jid.2022.03.029. Epub 2022 Apr 29.
BACKGROUND
Treatment options are limited for skin disease in dermatomyositis. Lenabasum is a cannabinoid receptor type 2 agonist that triggers the resolution of inflammation.
OBJECTIVE
The objective of this study was to evaluate the safety and efficacy of lenabasum in patients with refractory cutaneous dermatomyositis.
DESIGN
This study was a single-center, double-blind, randomized, placebo-controlled phase 2 study conducted from July 2015 to August 2017.
POPULATION
The population included subjects aged ≥18 years with at least moderately active dermatomyositis skin activity by Cutaneous Dermatomyositis Disease Area and Severity Index activity ≥ 14 and failure or intolerance to hydroxychloroquine.
INTERVENTION
Participants received 20 mg lenabasum daily for 28 days and then 20 mg twice per day for 56 days or placebo.
MAIN OUTCOMES AND MEASURES
The primary outcome was a change in Cutaneous Dermatomyositis Disease Area and Severity Index activity. Safety and other secondary efficacy assessments were performed till day 113.
RESULTS
A total of 22 subjects were randomized to lenabasum (n = 11) or placebo (n = 11). No serious or severe adverse events were related to lenabasum, and no participants discontinued the study. The adjusted least-squares mean for Cutaneous Dermatomyositis Disease Area and Severity Index activity decreased more for lenabasum, and the difference was significant on day 113 (least-squares mean [standard error] difference = ‒6.5 [3.1], P = 0.038). Numerically greater improvements were seen in multiple secondary efficacy outcomes and biomarkers with lenabasum.
CONCLUSION
Lenabasum treatment was well tolerated and was associated with greater improvement in Cutaneous Dermatomyositis Disease Area and Severity Index activity and multiple efficacy outcomes.
TRIAL REGISTRATION
This study was registered at ClinicalTrials.gov, NCT02466243.
背景
皮肌炎的皮肤病变治疗选择有限。利纳巴斯umab 是一种大麻素受体 2 激动剂，可引发炎症消退。
目的
本研究旨在评估利纳巴斯umab 在难治性皮肌炎皮肤病变患者中的安全性和疗效。
设计
这是一项单中心、双盲、随机、安慰剂对照的 2 期研究，于 2015 年 7 月至 2017 年 8 月进行。
人群
纳入的受试者年龄≥18 岁，皮肤肌炎疾病面积和严重程度指数（CDASI）活动评分≥14，且羟氯喹治疗失败或不耐受。
干预
参与者接受 20 mg 利纳巴斯umab 每日治疗 28 天，然后 20 mg 每日两次治疗 56 天，或安慰剂。
主要结局和措施
主要结局是 CDASI 活动的变化。安全性和其他次要疗效评估持续至第 113 天。
结果
共 22 名受试者随机分为利纳巴斯umab 组（n=11）或安慰剂组（n=11）。没有与利纳巴斯umab 相关的严重或严重不良事件，也没有参与者退出研究。利纳巴斯umab 组 CDASI 活动的调整最小二乘均数下降更明显，差异在第 113 天具有统计学意义（最小二乘均数[标准误差]差异=‒6.5[3.1]，P=0.038）。利纳巴斯umab 组在多个次要疗效终点和生物标志物上的改善更为显著。
结论
利纳巴斯umab 治疗耐受良好，与 CDASI 活动和多个疗效终点的改善更显著相关。
试验注册
本研究在 ClinicalTrials.gov 注册，NCT02466243。
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