Oral liarozole vs. acitretin in the treatment of ichthyosis: a phase II/III multicentre, double-blind, randomized, active-controlled study

Br J Dermatol. 2007 May;156(5):965-73. doi: 10.1111/j.1365-2133.2006.07745.x. Epub 2007 Jan 30.

Abstract

Background: Liarozole, a retinoic acid metabolism blocking agent, has been granted orphan drug status for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration.

Objectives: The purpose of this trial was to investigate the efficacy, tolerability and safety of oral liarozole vs. acitretin in patients with ichthyosis.

Methods: In this double-blind comparative trial of liarozole vs. acitretin, 32 patients with ichthyosis were randomized to be treated with either oral liarozole 75 mg in the morning and 75 mg in the evening or with acitretin 10 mg in the morning and 25 mg in the evening for 12 weeks. Clinical efficacy, tolerability and safety were monitored.

Results: Between-group comparisons for efficacy and tolerability revealed no statistically significant differences except for scaling on the trunk at baseline which was significantly worse in the liarozole group (P = 0.024) and showed a more pronounced improvement in this group than in the acitretin-treated patients (P = 0.047). Based on the overall evaluation of the response to treatment at endpoint, 10 of 15 patients in the liarozole group and 13 of 16 patients in the acitretin group were considered by the investigator to be at least markedly improved. The expected retinoic acid-related adverse events were mostly mild to moderate and tended to occur less frequently in the liarozole group. No serious adverse events related to the drugs occurred.

Conclusions: The present study indicates that liarozole at a daily dose of 150 mg is equally effective as a treatment for ichthyosis as acitretin but shows a trend towards a more favourable tolerability profile. The results of this trial warrant further clinical trials to confirm efficacy and safety of liarozole as an orphan drug in ichthyosis.

Publication types

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

MeSH terms

  • Acitretin / adverse effects
  • Acitretin / therapeutic use*
  • Administration, Cutaneous
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Dermatologic Agents / adverse effects
  • Dermatologic Agents / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Ichthyosis / drug therapy*
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Keratolytic Agents / adverse effects
  • Keratolytic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Dermatologic Agents
  • Imidazoles
  • Keratolytic Agents
  • liarozole
  • Acitretin