地拉瑞林治疗单纯型大疱性表皮松解症孤儿药研发：一项 2/3 期随机、安慰剂对照、双盲临床试验。

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial.

机构信息

EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.

INSERM UMR 1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France; University Paris Descartes-Sorbonne Paris Cité, Paris, France; Department of Genetics, Necker Hospital, AP-HP, Paris, France.

出版信息

J Am Acad Dermatol. 2018 May;78(5):892-901.e7. doi: 10.1016/j.jaad.2018.01.019. Epub 2018 Feb 2.

DOI:10.1016/j.jaad.2018.01.019

PMID:29410318

Abstract

BACKGROUND

Epidermolysis bullosa simplex (EBS) is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed.

OBJECTIVE

Compare the impact of 1% diacerein cream with placebo in reducing the number of blisters in EBS.

METHODS

In a randomized, placebo-controlled, phase 2/3 trial we used a 1% diacerein topical formulation to treat defined skin areas in 17 patients. In a 2-period crossover trial, patients were randomized to either placebo or diacerein for a 4-week treatment and a 3-month follow-up in period 1. After a washout, patients were crossed over during period 2. The prespecified primary end point was the proportion of patients with a reduction of number of blisters by more than 40% from baseline in selected areas over the treatment episode.

RESULTS

Of the patients receiving diacerein, 86% in episode 1 and 37.5% in episode 2 met the primary end point (vs 14% and 17% with placebo, respectively). This effect was still significant after the follow-up. Changes in absolute blister numbers were significant for the diacerein group only. No adverse effects were observed.

LIMITATIONS

Low patient numbers and no invasive data acquisition because of clinical burden in children.

CONCLUSION

This trial provides evidence of the impact of 1% diacerein cream in the treatment of EBS.

摘要

背景

单纯型大疱性表皮松解症（EBS）是一种罕见的遗传性水疱性皮肤病，目前尚无治愈方法。需要针对 EBS 的病理生理学进行治疗。

目的

比较 1%二乙酰瑞因乳膏与安慰剂在减少 EBS 水疱数量方面的作用。

方法

在一项随机、安慰剂对照、2/3 期试验中，我们使用 1%二乙酰瑞因局部制剂治疗 17 名患者的特定皮肤区域。在 2 期交叉试验中，患者随机分配至安慰剂或二乙酰瑞因治疗 4 周和第 1 期的 3 个月随访。洗脱期后，患者在第 2 期交叉。主要终点为在治疗期间选定区域的水疱数量减少超过 40%的患者比例。