IngentaConnect Oral liarozole in the treatment of palmoplantar pustular psoriasi...

Abstract:

Background Palmoplantar pustular psoriasis (PPP) is a chronic, relapsing condition often recalcitrant to therapy. Synthetic retinoids have been found to be efficacious in the treatment of PPP, but their use is limited by side-effects. Liarozole is an imidazole-like compound that inhibits the retinoic acid (RA) 4-hydroxylase-mediated breakdown of all-trans RA, causing elevation of plasma and cutaneous levels of RA. Thus liarozole acts as a retinoid-mimetic drug. Liarozole has already been found to be effective in the treatment of retinoid-responsive conditions such as chronic plaque psoriasis and ichthyoses.

Objectives To assess the efficacy and side-effect profile of liarozole in the treatment of PPP.

Methods We performed a double-blind, randomized, placebo-controlled trial of oral liarozole 75 mg twice daily for 12 weeks in the treatment of PPP. The trial was conducted at two centres and involved 15 patients.

Results Using the PPP Area and Severity Index we found a statistically significant (P = 0·02) improvement in PPP in subjects on liarozole (median 3, range 1·8–14·1) as compared with placebo (median 12·1, range 5–18) by the end of the treatment phase. There was also a statistically significant difference (P = 0·006) in the number of fresh pustules after treatment for the two study groups (liarozole median 2, range 0–18; placebo median 38, range 2–75). The severity of disease (on a scale of 0–8) between the two groups was significantly different at the end of treatment (liarozole median 1, range 1–5; placebo median 3, range 2–6; P = 0·04). No patients withdrew from the trial because of adverse events. The most commonly reported side-effects were pruritus, cheilitis and xerosis but these were rarely severe and resolved rapidly on discontinuation of treatment. Laboratory results, including haematology, liver function tests and serum cholesterol and triglycerides were not significantly different between the liarozole and placebo groups.

Conclusions The results of this pilot study suggest that liarozole 75 mg twice daily is an effective and well-tolerated therapy for PPP. In addition, the pharmacokinetics of liarozole may help to circumvent side-effects associated with synthetic retinoids and allow its use in premenopausal women.

Keywords: liarozole; P450; psoriasis; randomized controlled trial; retinoic acid; retinoid mimetic

Document Type: Research article

DOI: 10.1046/j.1365-2133.2001.04411.x

Affiliations: 1: Dermatology Centre, University of Manchester School of Medicine, Hope Hospital, Salford, Manchester M6 8HD, U.K. 2: Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. 3: Janssen-Cilag Limited, High Wycombe, U.K. 4: Janssen Research Foundation, Beerse, Belgium

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Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study