Inhibition of the metabolism of endogenous retinoic acid as treatment for severe psoriasis: an open study with oral liarozole.

Retinoids derived from retinol or beta-carotene are inactivated, among other ways, by enzymes belonging to the P450 cytochrome group. Liarozole, an imidazole-containing compound, is known to be a potent inhibitor of the cytochrome P450-mediated metabolism of all-trans retinoic acid. As a result, increased levels of this retinoid are found in skin and plasma. Therefore, in the treatment of psoriasis, therapeutic effects may be expected with liarozole which are similar to those observed with synthetic retinoids. In an open study, oral liarozole was given at a daily dose of 75 mg b.i.d., for 12 weeks to 31 patients with severe psoriasis. After 1 month, this dosage could be increased to 150 mg b.i.d. if there was no improvement or only moderate improvement. Initially, the effect of liarozole was mainly on scaling. A decrease in the Psoriasis Area and Severity Index (PASI) score of 45% at week 4, of 69% at week 8 and of 77% at week 12 was obtained, compared with baseline. A further decrease in the PASI score of up to 87% was observed in the 16 patients who were allowed to continue treatment for a maximum period of 12 months. An excellent or good improvement was noted in 77% of the patients within 12 weeks of starting treatment. This response rate had increased to 88% by the last follow-up visit. Nearly all patients (29 of 31) experienced adverse reactions, such as dry oral mucosa, headache and itching. These were mostly mild and transient, but four patients dropped out of the study because of an adverse event. Haematological, biochemical and cardiovascular parameters were not significantly influenced by liarozole. Six patients showed an increase in triglycerides, which normalized in three of four patients during further treatment. The results of this pilot study suggest that, at doses of 75-150 mg b.i.d., liarozole is an active antipsoriatic drug, and may be a useful addition to the existing therapeutic armamentarium. Controlled studies should be performed to compare liarozole with standard oral treatments.