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were withdrawn from treatment as a result of adverse events that may have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.