Acitretin-PUVA treatment schedule:
Acitretin monotherapy: Patients randomized to the acitretin group will receive acitretin in a
dose of 1mg /kg daily two weeks prior to additional PUVA treatment.
Acitretin-PUVA combination: PUVA treatment (see below) will be applied thrice weekly in
addition to acitretin until (near) complete clearance or over a maximum period of 12 weeks.
(Near) complete clearance is defined by improvement of the clinical baseline score (see
below) by ≥90%.
Acitretin maintenance therapy: After (near) complete clearance patients will be continued on
a maintenance dose of 0.5 mg/kg acitretin over 6 months or until significant relapse.
Significant relapse is defined by a worsening of the clinical score to ≥50 % of the baseline
score.
Follow-up period: Patients who are still significantly improved (clinical score of <50% of
the baseline score) will be followed up until significant relapse or over a maximum period of
12 months.
Besides emollients no additional specific treatments will be allowed during the study.
FAE-PUVA treatment schedule:
FAE monotherapy: Patients randomized to this group will receive FAE in weekly incremental
doses (initial daily dose: 30 mg dimethylfumarate (DMF), highest daily dose: 720 mg DMF)
starting two weeks prior to additional PUVA treatment.
FAE-PUVA combination: PUVA treatment will be applied thrice weekly in addition to FAE until
(near) complete clearance or over a maximum period of 12 weeks. (Near) complete clearance is
defined by improvement of the clinical baseline score (see below) by ≥90%.
FAE maintenance therapy: After (near) complete clearance FAE will be reduced weekly by 120 mg
DMF to a daily maintenance dose of 360 mg DMF which will be administered for a maximum period
of 6 months or until significant relapse. Significant relapse is defined by a worsening of
the clinical score to ≥50 % of the baseline score.
Follow-up period: Patients who are still significantly improved (clinical score of <50% of
the baseline score) will be followed up until significant relapse or over a maximum period of
12 months.
Besides emollients no additional specific treatments will be allowed during the study.
PUVA treatment:
Intake of 8-methoxypsoralen in a dose of 0.6 mg/kg 1 hour before UVA irradiation or, in case
of 8-methoxypsoralen intolerance, 5-methoxypsoralen in a dose of 1.2 mg/kg 2 hours before UVA
irradiation.
Start of PUVA 2 weeks after initiation of acitretin or FAE treatment. Irradiation will be
given three times per week over a maximum period of 12 weeks (36 exposures). PUVA exposure
will be limited to the hands and feet.
Primary outcome measure:
Duration of remission
Secondary outcome measures:
Percentage of patients achieving remission Number of PUVA exposures required for inducing
remission Total UVA exposure dose required for inducing remission Frequency and quality of
adverse reactions
Assessment of clinical response:
A modified local PASI (psoriasis area and severity index) score adapted for the evaluation of
the hands and feet will be performed by a blinded investigator at baseline and the onset of
PUVA treatment, in biweekly intervals during the course of PUVA treatment, in monthly
intervals after discontinuation of PUVA and in bimonthly intervals during a 1-year follow-up
period. The study will be terminated in case of a significant relapse which is defined by a
PASI score of ≥50 % of the baseline score.
Monitoring:
Prior to the study the blood chemistry, complete blood cell count including differential,
urine analysis, TSH, TPO- and TG autoantibodies, a pregnancy tests (in women of childbearing
potential) and an ophthalmological examination will be performed. During the study the
complete blood cell count, blood chemistry, urine analysis and pregnancy test (in women of
childbearing potential) will be reexamined monthly.