Comparative effects of calcipotriol solution (50 μg/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 μg/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). There was no statistically significant change in serum total calcium in either treatment group. There was no significant difference in the rate of relapse between the two treatment groups. In the 69 calcipotriol-treated patients who relapsed, re-treatment with calcipotriol was effective and well tolerated. Calcipotriol solution was effective in treating mild to moderate scalp psoriasis. However, betamethasone solution was significantly more effective, and was associated with statistically significantly less local irritation on the scalp and face.     

An investigator-masked comparison of the efficacy and safety of twice daily applications of calcitriol 3 µg/g ointment vs. calcipotriol 50 µg/g ointment in subjects with mild to moderate chronic plaque-type psoriasis

BACKGROUND: Calcitriol and calcipotriol, two vitamin D derivatives, are available for topical treatment of psoriasis and have been shown to be effective. AIM: To compare the efficacy and safety of calcitriol 3 microg/g and calcipotriol 50 microg/g. METHODS: This was a multicentre, randomized, investigator-masked, and parallel comparison in subjects with mild to moderate chronic plaque-type psoriasis receiving either calcitriol or calcipotriol ointment twice daily for 12 weeks. Efficacy evaluations comprised global improvement (on a 4-point scale from 0: no change or worse, to 3: clear or almost clear) assessed by the investigator and by the subject. Efficacy further included the 'dermatological sum score' at each study visit. Safety evaluations included adverse event reporting, cutaneous safety assessed by the investigator and cutaneous discomfort assessment by the subject (both on a 5-point scale from 0: none, to 4: very severe). RESULTS: A total of 250 subjects of both gender were recruited. At week 12, the LSmean score of global improvement rated by the investigator was 2.27 for calcitriol and 2.22 for calcipotriol. This difference was not statistically significant, with calcitriol demonstrating to be non-inferior to calcipotriol for global improvement. This same parameter was scored by the subject, with a mean of 2.12 for calcitriol and 2.09 for calcipotriol. The percentage of patients with at least marked improvement tended to be in favour of calcitriol (95.7% vs. 85% for calcipotriol). However, differences were not statistically significant. The mean worst score for the cutaneous safety assessment was higher in the calcipotriol group (0.3 vs. 0.1 and 0.4 vs. 0.2, by the investigator and the patient, respectively). These differences were statistically significant in favour of a better safety profile for calcitriol (P=0.0035). Fourteen dermatological and treatment-related adverse events were reported with calcipotriol vs. only five with calcitriol for a total of 22 adverse events reported throughout the study. CONCLUSION: Calcitriol administered twice daily over a 12-week treatment period demonstrated similar efficacy to calcipotriol, while showing a significantly better safety profile.     

The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy

Background: Although the use of an oral retinoid as monotherapy is an effective treatment for psoriasis, it is usually used in combination with other topical or systemic therapies including topical corticosteroids, UVB phototherapy, psoralens + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid adverse effects. Aim: To compare the efficacy of the calcipotriol + acitretin combination treatment with acitretin alone over a long period in Korean patients with psoriasis. Methods: A randomized, bilateral paired comparison was conducted involving 40 patients with psoriasis who received calcipotriol + acitretin combination therapy and 20 psoriasis patients who received acitretin alone. The initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and adverse effects. The maximum dose was 40 mg/day. The treatment duration for all patients ranged from 4–52 weeks. After 12 weeks, the efficacy of therapy, according to Psoriasis Area and Severity Index scores, was assessed. At the end of the study (52 weeks), we selected patients who had achieved complete clearance and compared the duration of treatment and total dose of acitretin used in both groups. Results: After 12 weeks, 16 patients (40%) achieved complete clearance in the calcipotriol + acitretin group and 3 patients (15%) in the acitretin monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy group achieved complete clearance. The duration of treatment and total dose of retinoid required to achieve clearance were slightly lower in the calcipotriol + acitretin combination group, however, this was not statistically significant. With the exception of liver enzyme elevation (which affected more patients in the acitretin monotherapy group than in the combination group), adverse effects were not significantly different. Discussion: Our results showed that calcipotriol might enhance the clinical outcome of systemic acitretin therapy. More large, well-controlled, long-term studies need to be conducted to determine whether there is indeed a beneficial effect of the addition of calcipotriol to acitretin treatment and whether this effect is maintained over long-term periods.     

Long-term safety of topical calcitriol 3 μg g−1 ointment

To assess the topical and systemic safety and tolerance of twice-daily application of 3 μg g⁻¹ 1α25-dihydroxyvitamin D₃ (calcitriol) ointment (Silkis ointment®, Galderma Laboratories) in the long-term treatment of patients suffering from chronic plaque psoriasis, we performed an open-design, multicentre study. Two hundred and fifty-three patients (155 males, 98 females) treated all their psoriatic lesions, except for those on the head and scalp, for up to 78 weeks. No serious adverse events were reported; 37 patients (14·6%) had a transient skin irritation reaction on one or more occasions during the study that resulted in study withdrawal for seven of them. The baseline/endpoint analyses showed no clinically relevant changes in measures of calcium and phosphorus homeostasis and renal function. Slight hypercalcaemia was observed in five (2%) patients; in four of these patients, serum albumin-adjusted total calcium levels normalized during treatment. In conclusion, twice-daily calcitriol 3 μg g⁻¹ ointment is safe and well tolerated in the long-term treatment of chronic plaque psoriasis.     

Efficacy of once-daily treatment regimens with calcipotriol/betamethasone dipropionate ointment and calcipotriol ointment in psoriasis vulgaris

BACKGROUND: A two-compound ointment containing calcipotriol 50 micro g g-1 and betamethasone dipropionate 0.5 mg g-1 has recently been shown to be an effective treatment for psoriasis. OBJECTIVES: This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 micro g g-1 ointment (Daivonex/Dovonex; LEO Pharma). METHODS: In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment. RESULTS: The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73.3% for group 1, 68.2% for group 2 and 64.1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55.3% for group 1, 47.7% for group 2 and 40.7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 (P < 0.001), whereas group 2 did not differ significantly from group 3. The difference between group 1 and group 2 was statistically significant with regard to PASI but not regarding the proportion of patients with absent/very mild disease. Patients receiving initial therapy with the two-compound product achieved the fastest treatment response, and the maximum treatment effect for these patients was seen after 5 weeks. This effect was maintained with continued treatment with the two-compound product for up to 8 weeks. After 12 weeks of treatment, no significant differences were seen between the three groups with regard to reduction in PASI, whereas the proportion of patients with absent/very mild disease in group 2 was superior to that in group 3. Patients receiving therapy with the two-compound product experienced fewer lesional/perilesional adverse drug reactions than the calcipotriol-treated patients (P < 0.001): 10.9% in group 1, 11.5% in group 2 and 22.3% in group 3. CONCLUSIONS: Two different short-term treatment regimens employing a recently developed two-compound product (calcipotriol/betamethasone dipropionate) provided rapid and marked clinical efficacy and were shown to be safe therapies for psoriasis vulgaris.     

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 μg/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 8weeks 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.     

钙泊三醇倍他米松软膏在银屑病治疗中的应用

钙泊三醇倍他米松软膏是卡泊三醇（50 μg/g）和倍他米松（0.5 mg/g）的复方制剂,两种活性成分通过不同的细胞受体发挥协同互补的药效学活性［１］。由于卡泊三醇和倍他米松保持稳定所需的pH值不同,卡泊三醇需要碱性环境来保持稳定性,而倍他米松需要的是酸性环境,因此两者混合时不能相容［2］。为此研发人员开发出了一种独特的、稳定的赋形剂克服两者不能相容的障碍,最终形成含有稳定活性成分的制剂。目前钙泊三醇倍他米松软膏已被应用于银屑病等皮肤病治疗中,我们概述近10年钙泊三醇倍他米松软膏在银屑病治疗中的应用……     

High-concentration (20 mug/g) tacalcitol ointment therapy on refractory psoriasis vulgaris with low response to topical corticosteroids

The efficacy and safety of the application of high-concentration (20 mug/g) tacalcitol ointment once daily for 12 weeks to psoriasis vulgaris lesions which showed low response to topical corticosteroids, were evaluated in a prospective, multicenter, open-label study. Eighty patients were enrolled in the safety analysis of the test drug, and 54 of the 80 patients in the efficacy analysis. The efficacy rate based on the number of cases graded as "moderate improvement" or better in the final global improvement rating of the 54 cases included in the efficacy analysis, was 88.9% (95% CI: 77.4-95.8%). Significant improvement in erythema, thickness, and scaling was observed from 2 weeks of treatment onward (p < 0.001). Five local adverse reactions (2 events of irritation, 2 events of itching, and 1 event of redness) were observed in 3 of the 80 patients included in the safety analysis. There were no significant changes in mean serum calcium values. Tacalcitol 20 mug/g ointment is concluded to be effective and safe for the treatment of refractory psoriasis vulgaris with low response to topical corticosteroids.     

No additional effect of calcipotriol ointment on low-dose narrow-band UVB phototherapy in psoriasis

BACKGROUND: Broad-band UVB phototherapy has appeared to be effective in clearing psoriatic lesions. After the advent of calcipotriol ointment, promising results have been obtained by combining these two therapeutic modalities. Also, an additional effect of narrow-band UVB phototherapy on treatment with calcipotriol ointment has been demonstrated. OBJECTIVE: Our purpose was to compare treatment with low-dose narrow-band UVB phototherapy both with and without calcipotriol ointment. METHODS: We included 53 patients suffering from plaque-type psoriasis. All patients underwent low-dose narrow-band UVB phototherapy. Nearly half of the patients were randomized to apply calcipotriol ointment (50 microg/g) twice daily on the affected skin. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic lesions. RESULTS: In this study we showed that low-dose narrow-band UVB phototherapy is effective in the treatment of psoriasis and that calcipotriol ointment does not improve treatment outcome. CONCLUSION: Calcipotriol ointment does not improve treatment with low-dose narrow-band UVB phototherapy.     

Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial,hairline, retroauricular or flexural areas

BACKGROUND: Psoriasis involving sensitive skin areas remains difficult to treat because of the side-effects of topical corticosteroids and the irritancy potential of vitamin D3 derivatives. Several clinical trials have demonstrated that calcitriol, the naturally occurring and hormonally active form of vitamin D3, is effective and safe at the dose of 3 microg g(-1) for the treatment of psoriasis affecting the trunk and limbs. METHODS: We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas. One pair of symmetrical and bilateral target lesions was selected from each area and assessed for perilesional erythema, oedema, and stinging/burning. Global assessment of local tolerability and global improvement were rated by the investigator, and the subjects were asked to evaluate the tolerability and efficacy of each product and to express their global preference. RESULTS: In the 75 subjects, calcitriol and calcipotriol both led to clearing of at least one target lesion in 21 (28%) of the subjects each. Perilesional erythema (P < 0.001), perilesional oedema (P < 0.02) and stinging/burning (P < 0.001) were all significantly less severe with calcitriol than with calcipotriol. The subjects' evaluation of local tolerability was significantly (P < 0.0001) in favour of calcitriol. Ten treatment-related dermatological events occurred in eight subjects, including one subject who experienced skin discomfort on both sides. All other events occurred only on the calcipotriol-treated side (irritant dermatitis, six subjects; contact dermatitis, one subject). Global assessment of improvement from baseline by the investigators was significantly greater for the calcitriol-treated lesions (P < 0.02). The subjects' global preference was significantly in favour of calcitriol (P < 0.02). CONCLUSIONS: In the present study, calcitriol ointment was found to be better tolerated and would appear to be more effective than calcipotriol ointment in the treatment of psoriasis in sensitive areas.     

A left/right comparison of twice-daily calcipotriol ointment and calcitriol ointment in patients with psoriasis: the effect on keratinocyte subpopulations

Vitamin D3 analogues are a first-line treatment of chronic plaque psoriasis, but so far, comparative clinical studies on calcipotriol and calcitriol ointment are sparse, and in particular no comparative studies are available on cell biological effects of these compounds in vivo. Using flow cytometric assessment, we investigated whether these compounds had different effects on the composition and DNA synthesis of epidermal cell populations responsible for the psoriatic phenotype. For 8 weeks, 20 patients with psoriasis vulgaris were treated twice daily with calcipotriol and calcitriol ointment in a left/right comparative study. Before and after treatment, clinical assessment of target lesions was performed, together with flow cytometric analysis of epidermal subpopulations with respect to keratin (K) 10, K6, vimentin and DNA distribution. Treatment with each compound resulted in a substantial clinical improvement, a reduction of the K10-K6- population and an increase of the K10+K6- population. A correlation was found between the clinical response of calcipotriol and the K10+K6- population, and the clinical response of calcitriol and the K10+K6- population, as well as the percentage of cells in the S, G2 and M phase of the cell cycle within the K10-K6- population, suggesting that the analogues have a different preference for affecting the K10+K6- pool (committed differentiated cells) or affecting the K10-K6- pool (basal cells).     

Long-term safety and efficacy of high-concentration (20 microg/g) tacalcitol ointment in psoriasis vulgaris

A multi-center open prospective research was conducted in order to assess the safety and efficacy of tacalcitol 20 microg/g ointment once daily (maximum 10 g/day) in the long-term treatment of psoriasis vulgaris. For the 74 subjects included in the 54-week efficacy analysis, the mean PASI score at the beginning of the study was 22.49 10.20 (mean SD), which was 5.73 6.04 after 54 weeks. A significant decrease (p < 0.001) in the mean PASI score was seen after 1 week of application, and the score remained almost constant after 18 weeks through 54 weeks. Twenty-five local adverse drug reactions were noticed in 16 of the 154 subjects included in the safety analysis. No increase in the incidence of severe adverse drug reactions was seen in the long-term administration of tacalcitol 20 microg/g ointment. Although a significant decrease in the intact parathyroid hormone (PTH) and 1alpha,25-(OH)2D3 was observed, the homeostasis of the corrected serum calcium was maintained. Tacalcitol 20 microg/g ointment, applied once daily at doses of up to 10 g/day (200 microg tacalcitol), is safe and effective, even in long-term administration, in the treatment of patients with psoriasis vulgaris. Serum calcium should be monitored in patients with decreased renal function and other suspected impairment of calcium metabolism, before and during the treatment with tacalcitol 20 microg/g ointment.     

阿维A治疗斑块状银屑病临床疗效观察

目的:观察阿维A治疗中、重度斑块状银屑病的疗效.方法:将中、重度斑块状银屑病患者随机分成两组,分别给予阿维A和海棠合剂治疗,疗程均为8周,以银屑病面积和严重度指数(PASI)和皮肤病生活质量指数(DLQI)作为观察指标,比较两种药物的疗效.结果:治疗后,两组患者的PASI评分和DLQI评分与治疗前比较均显著下降(P＜0.01),但PASI改善率和DLQI改善率两组间比较差异无统计学意义,PASI50和PASI75有效率亦无统计学意义(P＞0.05).结论:阿维A治疗中、重度斑块状银屑病有效.     

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)     

Efficacy and tolerance of topical calcitriol 3 μg g−1 in psoriasis treatment: a review of our experience in Poland

Although topical vitamin D₃ derivatives have been used in the treatment of patients with psoriasis for the past 15 years, questions remain about the indications and limitations of application. Extensive personal experience gained during the development of calcitriol (1α25-dihydroxyvitamin D₃) is therefore reviewed. Three double-blind, vehicle-controlled trials have revealed that calcitriol 3 μg g⁻¹ ointment (Silkis ointment®, Galderma Laboratories) has very good clinical efficacy. In a left–right comparison with vehicle ointment, complete clearance of psoriatic lesions was achieved in 48% of sites treated with calcitriol and a further 41% showed considerable or definite improvement. The clinical response to calcitriol in another study was as good as, or even better than, that achieved with betamethasone valerate 0·1% ointment. A preparation containing calcitriol 15 μg g⁻¹ did not show any clinical superiority to the lower dose but was associated with a higher risk of hypercalciuria, particularly when applied to extensive skin lesions. These results suggest that calcitriol 3 μg g⁻¹ ointment is an effective and safe treatment for chronic plaque psoriasis.     

吡硫翁锌气雾剂联合钙泊三醇倍他米松软膏序贯治疗斑块型银屑病的观察

目的观察吡硫翁锌气雾剂联合钙泊三醇倍他米松软膏序贯治疗斑块型银屑病的疗效以及安全性。方法 182例斑块状银屑病患者随机分为观察组和对照组,观察组90例应用吡硫翁锌气雾剂联合钙泊三醇倍他米松软膏外用治疗,对照组92例单用钙泊三醇倍他米松软膏外用治疗;两组疗程均为4周。结果观察组有效率为83.3%;对照组有效率为52.2%;两组比较差异均有统计学意义(P0.05)。结论应用吡硫翁锌气雾剂联合钙泊三醇倍他米松软膏序贯治疗银屑病起效快、副作用小。