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)     

钙泊三醇软膏治疗稳定期斑块型银屑病20例临床观察

银屑病是一种顽固性皮肤病，其病理改变主要为表皮过度增生及不完全分化，我科自１９９６年４月—１９９７年１月共对２０例银屑病患者外用钙泊三醇（大力士）软膏治疗，效果较满意，现报告如下。临床资料本组２０例男１３例，女７例，年龄３０—６０岁，病程２—３０年，...     

A comparative study of calcipotriol and anthralin for chronic plaque psoriasis in a day care treatment center

Eighteen patients with symmetric plaque-type psoriasis were recruited for an open, controlled, bilateral half-body comparison study to evaluate the efficacy of calcipotriol/tar/UVB vs. anthralin/tar/UVB in a day care treatment setting. No patient had been on systemic antipsoriatic agents for at least 3 months prior to enrolment. One half-body was arbitrarily assigned to treatment with gradually increasing concentrations of anthralin as tolerated. The other half-body received calcipotriol ointment twice daily. Both sides received UVB and additional coal tar distillate in accordance with our standard day care regimen. Patients who were admitted to the day care program attended the clinic for UVB, anthralin, and calcipotriol on weekdays for two consecutive weeks. Anthralin was applied to psoriatic plaques on one side in the following fashion: anthralin 0.1% with salicylic acid 3% in zinc oxide paste on days 1 and 2; anthralin 0.2% with salicylic acid 3% in zinc oxide paste on days 3–5; anthralin 1% with salicylic acid 3% in hydrophilic petrolatum for 60 min on days 8–10 to thicker lesions; and anthralin 2% with salicylic acid 3% in hydrophilic petrolatum for 60 min on day 11 to thicker lesions. On the contralateral side, calcipotriol ointment 0.05 μg/mL (Leo Pharmaceuticals, Ajax, Ontario) was applied to lesions twice daily. No anthralin or calcipotriol was applied on weekends. All patients applied coal tar oil 50% (Doak Oil Forte, Trans CanaDerm, St-Laurent, Québec, equivalent to 5% coal tar distillate) with salicylic acid 5% in hydrophilic petrolatum to their lesions at home in the evenings and on weekends. UVB (FSX72T12 lamps, National Biologic Corporation, Twinsburg, Ohio) was administered twice daily on weekdays in increasing doses as tolerated (to erythema) prior to the application of the topical medications. No trial medications were applied to the face, scalp, or genital regions. For clinical evaluation, the standard Psoriasis Activity and Severity Index (PASI) score¹ was modified by splitting the score for area under 10%; the modified score (mPASI) for an area of coverage of 1%–4% was 0.5 and for an area of 5%–9% was 1. The head and neck area was excluded from the analysis since neither anthralin nor calcipotriol was used at these sites. Each half-body was considered to represent 100% in the area score determination. The maximum modified score for each side was 64.8 (vs. 72 in the standard PASI scoring system¹). Clinical evaluations were completed at days 0 (baseline), 3, 7, 10, and 42. The primary end-point was day 10. On day 10, patients were asked to compare the calcipotriol ointment to the anthralin on a five-point scale in terms of efficacy and irritancy and to state their future preferred treatment modality. Following discharge from day care, patients were continued on outpatient UVB and tar treatments three times weekly and asked to return for a repeat clinical assessment after 4 weeks (day 42). Blood samples taken prior to treatment and at day 10 were analyzed for serum calcium. Comparisons of treatment efficacy were based on changes in the mPASI scores from onset of treatment to day 10, as well as on the corresponding percentage changes. Analyses were carried out using the Wilcoxon test. Subjective patient comparisons of effectiveness and irritancy, as well as patient preference, were tested for equiprobability using the chi-square goodness-of-fit test with an examination of the adjusted residuals.     

Comparison of calcipotriol and coal tar in conjunction with sun exposure in chronic plaque psoriasis: a pilot study

This study was a left-right comparison of the efficacy of 0.005% calcipotriol ointment and 5% coal tar ointment in conjunction with sun exposure in 10 patients with stable plaque psoriasis. After four weeks of therapy, the calcipotriol treated site showed a significantly faster fall in PASI compared to the coal tar treated site. At eight weeks, this difference was not significant with both sides showing comparable improvement in lesions, as shown by PASI values. There were no significant side effects from either therapy. We conclude that both calcipotriol and coal tar ointments have comparable efficacy in treating stable plaque psoriasis when used simultaneously with sun exposure, although the initial response to calcipotriol is faster.     

外用他克莫司与卡泊三醇治疗斑块状银屑病的疗效与安全性评价

目的:评价外用他克莫司和卡泊三醇软膏对四肢斑块状银屑病的疗效和安全性.方法:选取门诊斑块状银屑病患者,四肢左右两侧分别外用他克莫司软膏及卡泊三醇软膏,治疗2周及6周各复诊1次,观察四肢左右侧皮损消退情况,用单侧银屑病皮损面积及严重度指数(PASI)评分进行评价.结果:29例患者参加自身左右侧药物对比,有3例患者(10.3％)应用他克莫司后出现皮肤刺激症状而停用,其中1例患儿出现红皮病样改变.2周时有13例患者复诊,达到PASI50的患者中他克莫司侧4例,卡泊三醇侧5例;达到PASI75的患者中他克莫司侧1例,卡泊三醇侧2例.6周时14例患者复诊,达到PASI50的患者中他克莫司侧14例,卡泊三醇侧13例;达到PASI75的患者中他克莫司侧7例,卡泊三醇侧9例.2周及6周时比较双侧PASI50及PASI75,用Fisher精确概率检验法,发现两者差异无统计学意义.结论:对于四肢的斑块状银屑病,外用他克莫司和卡泊三醇软膏均有肯定疗效.部分患者应用他克莫司出现皮肤刺激症状,停药后症状多可消退.     

钙泊三醇倍他米松软膏治疗斑块状银屑病疗效评价

目的:评价钙泊三醇倍他米松软膏治疗斑块状银屑病的临床疗效。方法:治疗组(70例)给予钙泊三醇倍他米松软膏外用,对照组(56例)给予钙泊三醇软膏外用和5%松馏油软膏封包。结果:6周后治疗组有效率为88.57%,对照组有效率为75.00%,不良反应发生率分别为10.00%和23.75%,差异均有统计学意义(均P0.05)。结论:钙泊三醇倍他米松软膏外用治疗斑块状银屑病有效且相对安全。     

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.     

308nm准分子激光联合卡泊三醇软膏治疗斑块状银屑病疗效评价

目的：评价308 nm准分子激光联合卡泊三醇软膏治疗斑块状银屑病的临床疗效.方法：将93例稳定期斑块状银屑病随机分为3组,治疗组（33例） 予308 nm准分子激光照射,每周2次联合外搽卡泊三醇软膏,每日2次;对照1组（30例）外搽卡泊三醇软膏;对照2组（30例）,予308 nm准分子激光照射,方法同治疗组,2个月后判断疗效.结果：治疗组、对照1组和对照2组的有效率分别为90.91%、73.33%、63.33%.3组间疗效比较差异有统计学意义（均P〈0.05）.结论：308 nm准分子激光联合卡泊三醇软膏治疗斑块状银屑病能更好地提高疗效.     

Efficacy of calcipotriol ointment applied under hydrocolloid occlusion in psoriasis

BACKGROUND: Hydrocolloid (HCD) dressings enhance the efficacy of topical corticosteroids. OBJECTIVE: We wanted to evaluate the effect of calcipotriol ointment under an HCD dressing in the treatment of psoriatic plaques. METHODS: In 9 psoriatic patients, we cleared one plaque using this approach and took biopsies at start, clearance and relapse. Clinical and immunohistochemical validation was assessed. RESULTS: After an average treatment of 3.6 weeks, each lesion had cleared (apart from some residual erythema). The average remission period was 8 weeks. During this treatment, the number of cycling epidermal cells (Ki-67-positive nuclei) and the expression of keratin 14 and keratin 16 had decreased substantially. In biopsies taken from the skin immediately adjacent to the relapsing lesion, these markers remained reduced which indicated the prolonged effect of calcipotriol on epidermal differentiation. CONCLUSION: It is speculated that combination therapy of calcipotriol with treatments with a different mode of action such as photo(chemo)therapy, corticosteroids and cyclosporine might be worthwhile. Copyright (R) 2000 S.Karger AG, Basel     

钙泊三醇倍他米松软膏联合卡泊三醇软膏序贯治疗寻常型银屑病疗效评价

目的：评价钙泊三醇倍他米松软膏联合卡泊三醇软膏治疗寻常型银屑病的临床疗效。方法：30例银屑病患者全身左右侧皮损随机分为治疗组或对照组。治疗组外用钙泊三醇倍他米松软膏和卡泊三醇软膏;对照组外用卡泊三醇软膏。治疗第2、4、8周末进行疗效评价。结果：治疗2、4、8周后治疗组有效率（53.33%、70%和86.67%）均明显高于对照组（30%、46.67%和66.67%）,组间差异均有统计学意义（P〈0.05）。结论：钙泊三醇倍他米松软膏联合卡泊三醇软膏治疗寻常型银屑病疗效较单独使用卡泊三醇好。     

Combined treatment with low-dose cyclosporine and calcipotriol/betamethasone dipropionate ointment for moderate-to-severe plaque psoriasis: a randomized controlled open-label study

Combination therapy is a common approach to psoriasis, aimed at improving clinical response and minimizing the risk of side effects. The aim of this pilot randomized open-label study was to evaluate the efficacy and safety of the combination of low-dose cyclosporine (CsA) with calcipotriol-betamethasone dipropionate (CBD) ointment in the treatment of psoriasis. Sixty patients with moderate-to-severe plaque psoriasis were randomized to receive CsA, 2 mg/kg/day, combined with CBD ointment (n = 30) or CsA, at the same daily dosage, in combination with an emollient (n = 30), for 8 weeks. The primary efficacy parameter was the Psoriasis Area and Severity Index (PASI) 75 response rate at 8 weeks. Combination therapy with CsA and CBD ointment was more effective than CsA and emollient treatment, with statistically significant results, particularly less itching after 4 and 8 weeks and PASI reduction at all post-baseline visits. Significantly more patients treated with CsA + CBD achieved the PASI 75 at 8th week (87% vs 37% in the CsA-emollient group; p = 0.0001). The efficacy results were paralleled by the investigator and patient's global assessment of disease severity at the end of study. Our results suggest that the addition of CBD ointment to low-dose CsA enhances clinical response and improves the risk/benefit ratio.     

Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis

A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.     

Long-term outcome of severe chronic plaque psoriasis following treatment with high-dose topical calcipotriol

We have previously reported the effectiveness of high-dose calcipotriol in extensive psoriasis. We now report the long-term outcome in patients following this treatment. Twenty-eight patients with severe psoriasis were treated as in-patients with high-dose topical calcipotriol for 2 weeks. There was a mean reduction in the psoriasis area and severity index of 65%. Sixty-nine per cent were controlled for 3 months and 42% for 6 months. The relapse rate was comparable with that following Ingram's regimen, the in-patient stay was shorter and the treatment more acceptable. Careful monitoring of calcium homeostasis is mandatory.     

Tacalcitol ointment for long-term control of chronic plaque psoriasis in dermatological practice

BACKGROUND: Various studies have shown the benefit of topical vitamin D(3) analogues in the treatment of mild to moderate plaque psoriasis. OBJECTIVE: Assessment of the efficacy, tolerability and safety of tacalcitol ointment in the long-term treatment of chronic plaque psoriasis in daily dermatological practice. DESIGN AND METHODS: In this open, multicentre, clinical phase IV study with a pre/post comparison design, 157 patients with chronic plaque psoriasis were included. Patients showing chronic plaque psoriasis, covering 7-20% of their body area, were treated with tacalcitol ointment (4 microg/g, Curatoderm) once daily and were assessed at baseline and monthly during the 6-month treatment period. The efficacy parameter psoriasis area and severity index (PASI) and total body surface involvement were assessed at each visit. Laboratory parameters were assessed at the beginning and at the end of the study. Adverse events were recorded at each visit. RESULTS: The mean PASI score decreased by 67%, and a marked reduction in sum scores of erythema, infiltration and desquamation was detected. The body area affected declined by 33% from 13.3 to 8.8%. There were no changes in laboratory parameters, and no case of hypercalcaemia was observed. No serious adverse events occurred during the study period. The recorded local side-effects were usually transient and mainly mild. CONCLUSION: Tacalcitol ointment is safe, well tolerated and provides a further option for patients with psoriasis up to 20% body surface affected. Tacalcitol treatment can be recommended as effective therapy for long-term control of chronic plaque psoriasis in dermatological practice.     

Long-term efficacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis

BACKGROUND: As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term. OBJECTIVES: The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 microg g(-1)) ointment (Curatoderm, Hermal, Reinbek, Germany) applied once daily over a treatment period of 18 months. PATIENTS AND METHODS: Efficacy parameters were Psoriasis Area Severity Index (PASI), based on summed scores of erythema, infiltration and scaling and total body surface involvement (TBI). Safety assessment included serum levels of calcium, parathyroid hormone, calcitonin, 1,25-dihydroxy vitamin D3 (calcitriol); urinary calcium, creatinine, calcium/creatinine ratio in spot and 24-h urine and urinary alpha(1)-microglobulin. A group of 304 patients with chronic plaque psoriasis, covering between 7% and 20% of the body surface area was included for the initial treatment phase of 3 months. Of the 257 patients who completed the initial 3 months, 197 patients continued in a second treatment phase of 15 months. RESULTS: Tacalcitol treatment proved to be effective in reducing the severity of psoriasis and maintained therapeutic response over the study period. The median PASI fell from 9.5 to 4 .6 at month 3 and to 3.25 at month 18 (P < 0.0001). The median improvement in TBI was 30% at month 3 and 50% at month 18. In no patient was there any relevant disturbance of calcium homeostasis. There were no significant changes in mean values of serum calcium, parathyroid hormone and calcitriol. Additionally no significant changes in 24-h urinary excretion evaluation were observed. There was no correlation between levels of serum calcium or urinary calcium and amount of tacalcitol ointment used, even in the patients requiring the largest amounts of ointment (up to 13 g day(-1) and up to 20% of body area affected). Treatment was generally well tolerated and there were no serious or unexpected adverse events reported. However, discontinuation of treatment as a result of skin irritation was seen in 5.9% of patients. The greatest frequency of cutaneous side-effects occurred during initial treatment and the incidence decreased markedly as the treatment was well-tolerated with continued use. CONCLUSIONS: Tacalcitol ointment once daily was demonstrated to be efficacious, safe and well tolerated in the long-term control of plaque psoriasis in patients with up to 20% body surface involvement.     

国产卡泊三醇软膏治疗寻常性银屑病多中心临床研究

目的：临床多中心研究和验证卡泊三醇软膏治疗寻常型银屑病有效性与安全性。方法：采用随机、单盲、多中心平行对照的方法对64例寻常型银屑病患者应用0.005%卡泊三醇软膏（中国香港澳美制药厂生产,商品名：澳夫清?）每日2次,连续外用8周。在治疗2、4和8周后根据PASI评分和DLQI问卷调查评估疗效,并以丹麦利奥制药有限公司生产的0.005%卡泊三醇软膏（商品名：达力士?）治疗作为对照组,共63例。结果：试验组64例治疗8周后试验组痊愈9例、显效26例、进步19例、无效10例,总有效率54.68%,PASI评分由7.87±4.72下降至3.74±2.86。与对照组相比,两组有效性、总有效率和治疗前后PASI评分下降比较无统计学差异（χ2=2.6679,Z = -1.12,χ2 =1.550,P=0.1024,0.262,0.2153）;DLQI总分下降两组比较无统计学差异（P=0.8775）。治疗组和对照组发生局部刺激反应分别为7.8％和6.3％,无统计学差异（Fisher校正χ2检验P=1.0000）。结论：卡泊三醇软膏治疗寻常型银屑病有效、安全、耐受性良好。     

The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis

Background: Calcipotriol is an effective treatment of chronic plaque psoriasis. We have previously demonstrated that it has a small effect on systemic calcium homeostasis even at recommended doses. Objective: We attempted to determine the mechanism of the effect of calcipotriol on sytemic calcium homeostasis so we could assess the possible consequences of long-term use. Methods: Sixteen patients with extensive chronic plaque psoriasis were hospitalized and treated with high-dose topical calcipotriol. Up to 360 gm of calcipotriol (50 μg/gm) ointment was applied per week for 2 weeks under controlled conditions. Results: There was a dose-dependent rise in intestinal absorption of calcium. No effect on bone turnover was demonstrated over this short period. Five patients became hypercalcemic, and there was a dose-dependent rise in serum total adjusted calcium, serum ionized calcium, serum phosphate, urine calcium, and urine phosphate. There was a dose-dependent fall in serum parathyroid hormone and serum 1,25 dihydroxyvitamin D₃. Conclusion: Calcipotriol exerts its effects on systemic calcium homeostasis by increasing intestinal absorption of calcium and probably phosphate. This results in suppression of parathyroid hormone and 1,25 dihydroxyvitamin D₃. (J Am Acad Dermatol 1997;37:929-34.)     

Proactive treatment with calcipotriol reduces recurrence of plaque psoriasis

Topical calcipotriol is a widely used treatment for plaque‐type psoriasis worldwide, and has been shown to improve psoriatic plaques as well as very potent corticosteroids. However, there remains the practical question of whether calcipotriol application should continue on healed pigmentation/depigmentation associated with psoriatic plaques. Therefore, we conducted a pilot clinical study to answer this question. Plaque‐type psoriatic patients not receiving systemic treatment were enrolled and treated with calcipotriol for 8 weeks (stage I) to achieve maximum effect. The patients were then divided into two groups: group A continued to apply calcipotriol to the entirety of the previous lesion (including pigmentation/depigmentation) regardless of whether skin was healed or not, while group B applied calcipotriol to the remaining lesion only. Patients were followed for 12 weeks (stage II) and dates of plaque recurrence were recorded. A total of 29 patients (13 men, 16 women) were enrolled. During stage I, reductions in scores for redness, induration and scale occurred in 40%, 47% and 55% of patients, respectively. After stage II was completed, group A (n = 19) showed a significantly better Kaplan–Meier curve of non‐recurrence than group B (n = 8, P < 0.01). The mean non‐recurrence duration was 76.8 ± 11.8 in group A and 35.0 ± 12.0 in group B. Our study showed that applying topical calcipotriol on seemingly healed psoriatic plaque lesions suppresses recurrence better than applying it only on remaining plaques. This finding may be important for instructing psoriatic patients on topical calcipotriol treatment.