Treatment of psoriasis with oral liarozole: a dose-ranging study

Background Liarozole is an inhibitor of the metabolism of all-trans-retinoi c acid. Systemic administration increases tissue levels of this endogenous retinoid and has been reported to improve psoriasis in an open, uncontrolle d study. Objectives A multicentre, double-blind, placebo-controlled, dose-ranging st udy was therefore undertaken to determine the lowest effective oral dose of liarozole in the treatment of psoriasis vulgaris. Patients/methods Adult male and postmenopausal female patients requiring sy stemic treatment for psoriasis were randomized to receive placebo or liaroz ole at total daily doses of 50 mg, 75 mg or 150 mg for 12 weeks. The daily doses were each divided into two equal (morning and evening) doses. Respons e was assessed using an eight-point global scale to assess improvement and by monitoring the Psoriasis Area and Severity Index (PASI). The primary end -point was the proportion of subjects in each treatment group demonstrating 'marked improvement' or better as assessed on the eight-point scale. The t olerability of the treatment was assessed by recording mucocutaneous effect s of retinoids and all adverse events. Biochemical and haematological monit oring were also performed. Results One hundred and thirty-nine subjects were randomized (118 male and 21 female) and 116 completed the study. A marked improvement or better resp onse was observed in 6% of subjects on placebo, 18% on liarozole 50 mg, 11% on 75 mg and 38% on 150 mg. Only in the 150-mg group was the response rate significantly different to placebo (P < 0.001). Over the treatment period the mean PASI changed from 15.9 to 15.4 on placebo, from 17.4 to 13.8 on li arozole 50 mg, from 17.5 to 14.5 on 75 mg and from 15.8 to 8.8 on 150 mg. A gain, only in the group receiving 150 mg was the response significantly bet ter than placebo (P < 0.001). Liarozole was generally well tolerated, Mucoc utaneous retinoid effects were generally infrequent and mild. Five subjects were withdrawn from treatment as a result of adverse events that may have been treatment related. These events were abnormalities of liver enzymes in two cases, an episode of erythema multiforme (in a patient receiving place bo), an allergic reaction in one and a rash accompanied by deterioration of the psoriasis in another. There was mild elevation of triglycerides in the groups receiving liarozole 75 mg and 150 mg daily. In males, the serum lut einizing hormone and testosterone levels rose significantly in all the acti ve treatment groups. Conclusions The data confirm that liarozole is an effective treatment for p soriasis and indicate that the lowest effective dose is 75 mg twice daily. The drug seems generally to be well tolerated.