The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial.

BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.

Safety and efficacy of calcipotriol ointment (Dovonex) in treating children with psoriasis vulgaris.

Calcipotriol (Dovonex) ointment has been shown to be an effective, well tolerated, and acceptable treatment for psoriasis vulgaris in adults. This open study was conducted in 16 U.K. centres to assess the safety and efficacy of calcipotriol ointment in treating psoriasis vulgaris in children. Following a 2-week washout, patients were treated with calcipotriol ointment, 50 micrograms/g twice daily, for up to 8 weeks. A blood sample was taken on entry and a second 'on treatment' sample was taken after either 2 or 8 weeks treatment. Sixty-six children (26 boys, 40 girls, age range from 3 to 14 years) entered and 58 completed the study. There was a statistically significant reduction in the mean (+/- SD) Psoriasis Area and Severity Index (PASI) from 6.1 +/- 3.5 at the start of treatment to 2.7 +/- 1.9 at the end of treatment (P < 0.001). Marked improvement or clearance of psoriasis at the end of treatment occurred in 65% of patients as assessed by the investigator and 62% as assessed by the patient. Cosmetic acceptability of calcipotriol ointment was found to be good or excellent in 79% of patients. Eight patients withdrew from the study (four defaulted, two unacceptable responses, two adverse events). Adverse events were reported by 16 patients: the most common being local irritation (seven patients). There was no significant change in the mean serum ionized calcium from baseline to 2 or 8 weeks treatment. Similarly, there were no consistent or clinically important changes in haematological, or other biochemical parameters, measured during the study period. Calcipotriol ointment has been shown to be an effective, well tolerated, and acceptable treatment for psoriasis vulgaris in children.

Comparative effects of calcipotriol solution (50 micrograms/ml) and betamethasone 17-valerate solution (1 mg/ml) in the treatment of scalp psoriasis.

The efficacy, tolerability and safety of calcipotriol solution and betamethasone 17-valerate solution were compared in a multicentre, prospective, randomized, double-blind, parallel group study. Four hundred and seventy-four patients with scalp psoriasis were recruited from six European countries and Canada. Following a 2-week washout period, either calcipotriol solution (50 micrograms/ml) or betamethasone 17-valerate solution (1 mg/ml) was applied twice daily for 4 weeks. After this time, patients who required no further active treatment were observed for relapse. Retreatment with calcipotriol was offered to those patients who relapsed, and who were originally in the calcipotriol-treated group. The two treatment groups were well matched at baseline. At the end of treatment, the proportion of patients who had 'cleared' or 'markedly improved' was statistically significantly greater in the betamethasone group (75%) than in the calcipotriol group (58%) (P < 0.001) (95% confidence interval of difference 25.3-->8.6). The decrease in total sign score (sum of scores for erythema, thickness and scaliness) at the end of treatment was also statistically significantly greater in the betamethasone group (61%) than the calcipotriol group (45%) (P < 0.001) (95% confidence interval of difference 9.7-->23.1). Adverse events were reported by 87 patients in the calcipotriol group, and 31 patients in the betamethasone group; the most common was lesional or perilesional irritation, which occurred significantly more frequently with calcipotriol (26%) than with betamethasone (8%) (P < 0.001). Fifteen patients (6%) in the calcipotriol group and four (1%) in the betamethasone group withdrew from the study because of adverse events or unacceptable treatment response (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis.

Short-contact treatment with dithranol (anthralin) is a widely used treatment for chronic plaque psoriasis. Although effective, it causes staining and irritation, and is therefore inconvenient. Calcipotriol is a recently developed vitamin D analogue which is effective and easy to use. To evaluate the relative efficacy, safety and acceptability of these treatments a multicentre, open, randomized, parallel-group comparison was performed. Four hundred and seventy-eight patients with chronic plaque psoriasis were randomized to use one of the two treatments for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice daily. The other used a single application for 30 min each day of Dithrocream in the highest concentration tolerated. Severity of psoriasis was assessed by modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five-point scale was used by subjects and by investigators as an additional assessment of overall response, and a similar scale was used by subjects to grade acceptability. Total serum calcium was monitored at baseline and after 2 and 8 weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The difference between the two treatments was significant in favour of calcipotriol at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the difference between mean improvements in scores for the two groups was 1.6 (95% confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and acceptability grading by subjects, were all significantly better for calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Prophylaxis against herpes labialis with acyclovir cream--a placebo-controlled study.

Patients with 6 or more recurrences per year of herpes labialis were entered into a randomized, double-blind, placebo-controlled, crossover study. During the trial, they applied acyclovir cream for 16 weeks and placebo cream for 16 weeks to all previously affected areas 4 times per day, and were subsequently observed for a further 16 weeks with no treatment. Results from the 23 evaluable cases showed that although recurrences did occur whilst on acyclovir treatment, patients suffered from significantly fewer days of disease and significantly fewer attacks of cold sores when compared with placebo.

Failure of acyclovir cream in treatment of recurrent herpes labialis.

A double blind, randomised, crossover placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 45 patients with recurrent herpes labialis. These patients had a total of 72 episodes, 34 of which were treated with the 5% acyclovir cream and 38 with placebo cream. Treatment was begun by the patients as soon as possible after the onset of prodromal symptoms. There was no significant clinical benefit from treatment with acyclovir cream compared with placebo cream. The median healing times were nine days with acyclovir cream, 10 days with placebo cream, and 13 days when no treatment was given. The possibility that the 40% propylene glycol cream base alone has a therapeutic effect must therefore be considered.

Rapid cytological diagnosis of basal cell carcinoma of the skin.

Cytological diagnosis in a series of 153 skin lesions is presented. The diagnosis in each case has been compared with the clinical assessment and, where available, the biopsy result (85 lesions). Of 131 basal cell carcinomas, a cytological diagnosis was possible in 124 while biopsyl failed to identify two of the 73 lesions studied. A correct cytological diagnosis was made in five squamous cell carcinomas and in one malignant melanoma. Basal cell papillomas and solar keratoses were not accurately identified. We thus conclude that with this very simple, rapid, and inexpensive method a clinical diagnosis of basal cell carcinoma is reliably confirmed with advantages for both the clinic and the laboratory.

Alopecia areata: immunofluorescence and other studies.

In a study of 24 patients with alopecia areata, scalp biopsies were examined for immunofluorescence; all were negative. A number of other tests also failed to confirm an auto-immune aetiology for this disease. A possible explanation lies in the heterogeneity of alopecia areata, only a small proportion of cases being of the auto-immune type.