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Notes: Objectives To investigate the therapeutic efficacy of acitretin + PUVA compared to placebo + PUVA in terms of improvement assessed by the Psoriasis Severity Index (PSI) and total UVA dosage.Design Double-blind, randomized, parallel, multicenter study over 8 weeks.Indication Generalized chronic plaque or exanthematic type of psoriasis severe enough to require PUVA treatment.Targets Decrease of PSI at the end of the study; response defined as improvement of PSI≥ 75% with respect to baseline, total UVA dosage applied and UVA dosage applied up to response.Statistical methods PSI changes (baseline up to end of treatment) in the two groups were compared at the 5% significance level using the Kolmogoroff-Smirnoff test (2-tailed). In addition, descriptive statistics for comparison of response rates (Chi2 test) and total UVA dosage as well as UVA dosage applied up to response (life-table analysis by Kaplan-Meier) were performed.Results Patients Forty patients (36 males. 4 females) in the placebo + PUVA and 43 patients (32 males, 11 females) in the placebo + PUVA group were investigated for efficacy. Twenty-three patients of the acitretin + PUVA group and 25 patients of the placebo + PUVA group ceased treatment prematurely. PSI The median PSI decrease was 24 (89%) score points in the acitretin + PUVA group and 21 (83%) in the placebo + PUVA group (P 〉 0.05, Kolmogoroff-Smirnoff test). The response rate was 34 out of 40 (85%; 95% CI 70-94%) in the acitretin + PUVA group and 26 out of 43 (60%; 95% CI 44–75%) in the placebo + PUVA group (P= 0.013. Chi2 test: descriptive). Complete remission The clinical outcome as assessed by the investigator was complete remission in 28 patients of the acitretin + PUVA group and 19 patients of the placebo + PUVA group. Premature discontinuation of treatment due to complete remission was possible in 16 patients of the acitretin + PUVA group and 11 patients of the placebo + PUVA group. UVA dosage The total UVA dose applied was 77.6 J/cm2 (SEM = 9.2 J/cm2) in the acitretin + PUVA group and 73.0 I/cm2 (SEM = 7.2 J/cm2) in the placebo + PUVA group. The median UVA dose up to response was 52.0 J/cm2 in the acitretin + PUVA group and 74.5 J/cm2 in the placebo + PUVA group. Tolerability In both treatment groups, adverse events were frequent. Mucocutaneous adverse events, such as dry lips, mouth and nose and dryness and scaling of the skin, were the most common complaints in both groups, but more pronounced in the acitretin + PUVA group. Treatment of adverse events included mainly indifferent ointments, non-steroidal, anti-inflammatory drugs and anti-puritic agents and tranquilizers. Treatment had to be discontinued due to adverse events in three patients of each group. In the acitretin + PUVA group, the reasons were acral-bullous photodermatosis due to PUVA, increased liver enzymes and increased triglycerides, respectively. In the placebo + PUVA group, one patient developed sensori-neural loss of hearing, one stomach pain, nausea and colics of the upper abdomen and one increased triglycerides, cholesterol and liver enzymes.Conclusions Difference in improvement of the PSI was not statistically significant between the acitretin + PUVA and the placebo + PUVA groups. However, the response rates (75% PSI decrease) and complete remission as assessed by the investigator for acitretin + PUVA was superior to PUVA alone. The UVA-saving effect could not be confirmed although the UVA dose applied up to response was less in the acitretin + PUVA group. Overall, acitretin was found to enhance the therapeutic efficacy of PUVA in patients with severe psoriasis.