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

A Vahlquist, S Blockhuys, P Steijlen, K van Rossem, B Didona, D Blanco, H Traupe, A Vahlquist, S Blockhuys, P Steijlen, K van Rossem, B Didona, D Blanco, H Traupe

Abstract

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.

© 2013 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Figures

Figure 1
Figure 1
Patient flow diagram.
Figure 2
Figure 2
Patient with lamellar ichthyosis (a) at baseline and (b) after 12 weeks of treatment with once-daily liarozole (150 mg). Marked improvement of scaling from severe [Investigator's Global Assessment (IGA) score of 4] at baseline to almost clear (IGA score of 1) after treatment is observed.
Figure 3
Figure 3
Mean Investigator's Global Assessment (IGA) score over time (intent-to-treat population, last observation carried forward). For results of post hoc statistical analysis, see Table S1.
Figure 4
Figure 4
Mean symptom scores over time: (a) scaling, (b) erythema and (c) pruritus (intent-to-treat population; last observation carried forward). For results of post hoc statistical analysis, see Table S1.

References

    1. Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009. J Am Acad Dermatol. 2010;63:607–41.
    1. Vahlquist A, Ganemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol. 2008;88:4–14.
    1. Oji V, Traupe H. Ichthyoses: differential diagnosis and molecular genetics. Eur J Dermatol. 2006;16:349–59.
    1. Hernandez-Martin A, Garcia-Doval I, Aranegui B, et al. Prevalence of autosomal recessive congenital ichthyosis: a population-based study using the capture–recapture method in Spain. J Am Acad Dermatol. 2012;67:240–4.
    1. Ganemo A, Lindholm C, Lindberg M, et al. Quality of life in adults with congenital ichthyosis. J Adv Nurs. 2003;44:412–19.
    1. Kamalpour L, Gammon B, Chen KH, et al. Resource utilization and quality of life associated with congenital ichthyoses. Pediatr Dermatol. 2011;28:512–18.
    1. Summary of Product Characteristics, 2011. Neotigason 10 mg capsules. Available at: (last accessed 23 October 2013)
    1. Medication guide for patients. Soriatane capsules, 2011. Available at: (last accessed 23 October 2013)
    1. Barrier Therapeutics, Inc. Barrier Therapeutics granted European orphan drug status for liarozole, 2003. Available at: (last accessed 23 October 2013)
    1. Barrier Therapeutics, Inc. Barrier Therapeutics' liarozole receives FDA orphan drug status, 2004. Available at: (last accessed 23 October 2013)
    1. Verfaille CJ, Borgers M, van Steensel MA. Retinoic acid metabolism blocking agents (RAMBAs): a new paradigm in the treatment of hyperkeratotic disorders. J Dtsch Dermatol Ges. 2008;6:355–64.
    1. Lucker GP, Heremans AM, Boegheim PJ, et al. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole. Br J Dermatol. 1997;136:71–5.
    1. Verfaille CJ, Vanhoutte FP, Blanchet-Bardon C, et al. Oral liarozole vs. acitretin in the treatment of ichthyosis: a phase II/III multicentre, double-blind, randomized, active-controlled study. Br J Dermatol. 2007;156:965–73.
    1. World Medical Association. 2008. World Medical Association Declaration of Helsinki; ethical principles for medical research involving human subjects. Available at: (last accessed 23 October 2013)
    1. Ware JE., Jr SF-36 health survey update. Spine (Phila Pa 1976) 2000;25:3130–9.
    1. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19:210–16.
    1. Lewis V, Finlay AY. 10 years' experience of the Dermatology Life Quality Index (DLQI) J Investig Dermatol Symp Proc. 2004;9:169–80.

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