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

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

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.

Keywords: diacerein; epidermolysis bullosa; keratin; rare genodermatosis.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Anthraquinones / therapeutic use*
  • Anti-Inflammatory Agents
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Epidermolysis Bullosa Simplex / diagnosis*
  • Epidermolysis Bullosa Simplex / drug therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Orphan Drug Production*
  • Patient Compliance
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Anthraquinones
  • Anti-Inflammatory Agents
  • diacetylrhein