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Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial

SUMMARY: BACKGROUND: Oral liarozole, a retinoic acid metabolism-blocking agent, may be an alternative to systemic retinoid therapy in patients with lamellar ichthyosis. OBJECTIVE: To demonstrate the efficacy and safety of once-daily oral liarozole in the treatment of moderate/severe lamellar ichthyo...

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Autores principales: Vahlquist, A, Blockhuys, S, Steijlen, P, van Rossem, K, Didona, B, Blanco, D, Traupe, H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232915/
https://www.ncbi.nlm.nih.gov/pubmed/24102348
http://dx.doi.org/10.1111/bjd.12626
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author Vahlquist, A
Blockhuys, S
Steijlen, P
van Rossem, K
Didona, B
Blanco, D
Traupe, H
author_facet Vahlquist, A
Blockhuys, S
Steijlen, P
van Rossem, K
Didona, B
Blanco, D
Traupe, H
author_sort Vahlquist, A
collection PubMed
description SUMMARY: BACKGROUND: Oral liarozole, a retinoic acid metabolism-blocking agent, may be an alternative to systemic retinoid therapy in patients with lamellar ichthyosis. OBJECTIVE: To demonstrate the efficacy and safety of once-daily oral liarozole in the treatment of moderate/severe lamellar ichthyosis. METHODS: This was a double-blind, multinational, parallel phase II/III trial (NCT00282724). Patients aged ≥ 14 years with moderate/severe lamellar ichthyosis [Investigator's Global Assessment (IGA) score ≥ 3] were randomized 3 : 3 : 1 to receive oral liarozole (75 or 150 mg) or placebo once daily for 12 weeks. Assessments included: IGA; a five-point scale for erythema, scaling and pruritus severity; Short Form-36 health survey; Dermatology Life Quality Index (DLQI); and safety parameters. The primary efficacy variable was response rate at week 12 (responder: ≥ 2-point decrease in IGA from baseline). RESULTS: Sixty-four patients were enrolled. At week 12, 11/27 (41%; liarozole 75 mg), 14/28 (50%; liarozole 150 mg) and one out of nine (11%; placebo) patients were responders; the difference between groups (liarozole 150 mg vs. placebo) was not significant (P = 0·056). Mean IGA and scaling scores decreased from baseline in both liarozole groups at weeks 8 and 12 vs. placebo; erythema and pruritus scores were similar between treatment groups. Improvement in DLQI score was observed in both liarozole groups. Treatment with liarozole for 12 weeks was well tolerated. CONCLUSIONS: The primary efficacy variable did not reach statistical significance, possibly owing to the small sample size following premature termination. However, once-daily oral liarozole, 75 and 150 mg, improved scaling and DLQI and was well tolerated in patients with moderate/severe lamellar ichthyosis.
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spelling pubmed-42329152014-12-29 Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial Vahlquist, A Blockhuys, S Steijlen, P van Rossem, K Didona, B Blanco, D Traupe, H Br J Dermatol Original Articles SUMMARY: BACKGROUND: Oral liarozole, a retinoic acid metabolism-blocking agent, may be an alternative to systemic retinoid therapy in patients with lamellar ichthyosis. OBJECTIVE: To demonstrate the efficacy and safety of once-daily oral liarozole in the treatment of moderate/severe lamellar ichthyosis. METHODS: This was a double-blind, multinational, parallel phase II/III trial (NCT00282724). Patients aged ≥ 14 years with moderate/severe lamellar ichthyosis [Investigator's Global Assessment (IGA) score ≥ 3] were randomized 3 : 3 : 1 to receive oral liarozole (75 or 150 mg) or placebo once daily for 12 weeks. Assessments included: IGA; a five-point scale for erythema, scaling and pruritus severity; Short Form-36 health survey; Dermatology Life Quality Index (DLQI); and safety parameters. The primary efficacy variable was response rate at week 12 (responder: ≥ 2-point decrease in IGA from baseline). RESULTS: Sixty-four patients were enrolled. At week 12, 11/27 (41%; liarozole 75 mg), 14/28 (50%; liarozole 150 mg) and one out of nine (11%; placebo) patients were responders; the difference between groups (liarozole 150 mg vs. placebo) was not significant (P = 0·056). Mean IGA and scaling scores decreased from baseline in both liarozole groups at weeks 8 and 12 vs. placebo; erythema and pruritus scores were similar between treatment groups. Improvement in DLQI score was observed in both liarozole groups. Treatment with liarozole for 12 weeks was well tolerated. CONCLUSIONS: The primary efficacy variable did not reach statistical significance, possibly owing to the small sample size following premature termination. However, once-daily oral liarozole, 75 and 150 mg, improved scaling and DLQI and was well tolerated in patients with moderate/severe lamellar ichthyosis. BlackWell Publishing Ltd 2014-01 2014-01-13 /pmc/articles/PMC4232915/ /pubmed/24102348 http://dx.doi.org/10.1111/bjd.12626 Text en © 2013 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Vahlquist, A
Blockhuys, S
Steijlen, P
van Rossem, K
Didona, B
Blanco, D
Traupe, H
Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial
title Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial
title_full Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial
title_fullStr Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial
title_full_unstemmed Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial
title_short Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial
title_sort oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase ii/iii trial
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232915/
https://www.ncbi.nlm.nih.gov/pubmed/24102348
http://dx.doi.org/10.1111/bjd.12626
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