Comparison of calcipotriol monotherapy and a combination of calcipotriol and betamethasone valerate after 2 weeks' treatment with calcipotriol in the topical therapy of psoriasis vulgaris: a multicentre, double-blind, randomized study

A clinical study was conducted to determine whether, in the topical treatment of psoriasis, a combination of calcipotriol and betamethasone valerate after previous treatment with calcipotriol alone was more effective than the continuation of the monotherapy with calcipotriol, especially in 'low responders'. Patients ( n  = 169) with the clinical diagnosis 'chronic plaque-type psoriasis' were treated twice daily for 2 weeks with calcipotriol, followed by a 4-week treatment with calcipotriol monotherapy in 87 patients or combined calcipotriol/betamethasone valerate in 82 patients; all patients were followed for 8 weeks. The psoriasis area and severity index (PASI) was used to compare the two treatment groups. The overall therapeutic result was also assessed by the investigators and patients. The combination therapy was more effective, as assessed by all evaluated variables; moreover, patients showing insufficient response to calcipotriol alone after 2 weeks showed a regression of psoriatic lesions using the combination regimen. Thus, the combination of calcipotriol and topical steroids is recommended as the therapy of first choice for patients who do not respond well to treatment with 2 weeks of calcipotriol alone. Furthermore, this combination reduces the hazards associated with the long-term use of topical corticosteroids (atrophy and rebound) as well as the irritation associated with calcipotriol.     

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.     

A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis

The antipsoriatic efficacy, tolerability and safety of calcipotriol ointment was compared with tar in a prospective, right/left randomized, investigator-blinded controlled study. Calcipotriol ointment 50 μg/g twice daily was applied to one-half of the body. On the opposite side, white soft paraffin was applied in the morning, and coal tar solution BP 15% v/w in aqueous cream in the evening. Thirty patients with stable chronic plaque-type psoriasis were recruited. Assessments were made at 2,4 and 6 weeks. Three patients were withdrawn from the study. A decrease in PASI score was seen on both sides at 2, 4 and 6 weeks. The differences from baseline between the two treatments were statistically significant in favour of calcipotriol. Improvement with calcipotriol was rapid in the first 2 weeks of treatment. With tar, significant improvement occurred only after 4 weeks of treatment. The differences in the scores for erythema, induration and desquamation from baseline between the two treatments were also statistically significantly in favour of calcipotriol at all evaluation points. Seven patients developed irritation on the calcipotriol-treated side, but there were no adverse effects on the tar-treated side. In two patients, itching associated with psoriasis was reduced by the calcipotriol. Although the mean serum calcium and phosphate levels remained within the normal ranges after 6 weeks' treatment, there were significant changes in their values compared with baseline.     

A randomized, controlled clinical trial comparing photochemotherapy with dithranol in the initial treatment of chronic plaque psoriasis

224 patients with widespread plaque psoriasis were randomly allocated to treatment with PUVA or dithranol. 103 of the 113 patients treated with PUVA (91.2%) cleared satisfactorily compared with 91 out of in patients treated with dithranol (82%). However, dithranol cleared psoriasis significantly faster than PUVA (20.4±0.9 days compared to 34.4±1.8 days). Photochemotherapy produced no evident short-term adverse effects on the bone marrow, liver, or kidneys.     

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.     

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.     

Epidermal cytokeratin and immunocyte responses during treatment of psoriasis with calcipotriol and betamethasone valerate

Changes in epidermal immunocytes and cytokeratins were investigated during treatment of psoriasis with calcipotriol and betamethasone valerate. Skin biopsies were obtained from 10 subjects on each treatment from lesional and non-lesional skin at baseline, and from treated lesions after 4 weeks. In each subject, changes in expression of cytokeratins K5, K10 and K16, and changes in epidermal immunocyte counts were assessed. Responses were compared with a separate histological parameter of improvement, epidermal thickness. Both treatments produced a marked normalization of cytokeratins. The reduction of K16 expression was similar on each treatment and correlated significantly with reduction in epidermal thickness. Expression of both K5 and K10 improved less than thickness with betamethasone valerate but more than thickness with calcipotriol, although these differences did not reach statistical significance. With calcipotriol there was an increase in K5 and K10 responses with increasing response of epidermal thickness, which was not seen with betamethasone valerate. T6+ cells, HLA-DR+ dendritic cells and T lymphocytes were all reduced by betamethasone valerate. There was a remarkable similarity in the level of normalization between cell types and also between cellular response and reduction in thickness. Calcipotriol produced a similar consistent reduction in cell numbers and in thickness, with the exception of T6+ cells which increased in some subjects during treatment. Only in subjects in whom thickness had virtually returned to normal was there a marked decrease in T6+ cells.     

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.     

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.     

An international,randomized, double-blind,placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis

BACKGROUND: Alefacept, human lymphocyte function-associated antigen 3/immunoglobulin 1 fusion protein, binds to CD2 molecules on the surface of activated T cells, selectively targeting memory-effector (CD45RO+) T cells, which comprise more than 75% of T cells in psoriatic plaques. OBJECTIVE: To examine the efficacy and tolerability of intramuscular alefacept. DESIGN: International, randomized, double-blind, placebo-controlled, parallel-group trial. PATIENTS: A total of 507 patients with chronic plaque psoriasis. INTERVENTION: Placebo, 10 mg of alefacept, or 15 mg of alefacept administered once weekly for 12 weeks followed by 12 weeks of observation. MAIN OUTCOME MEASURE: Psoriasis Area Severity Index (PASI). RESULTS: Alefacept treatment was associated with dose-related significant improvements in PASI from baseline. Throughout the study, a greater percentage of patients in the 15-mg group than in the placebo group achieved a significant reduction in PASI. Of patients in the 15-mg group who achieved at least 75% PASI reduction 2 weeks after the last dose, 71% maintained at least 50% improvement in PASI throughout the 12-week follow-up. There were no opportunistic infections and no cases of disease rebound. CONCLUSION: Intramuscular administration of alefacept was a well-tolerated and effective therapy for chronic plaque psoriasis and thus represents a convenient alternative to intravenous dosing.     

A randomized,double-blind,placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis

BACKGROUND: In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable. OBJECTIVE: Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis. METHODS: Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course. RESULTS: During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P <.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses. CONCLUSION: Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.     

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)     

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.)     

【开放获取】丙酸氟替卡松乳膏单独或联合卡泊三醇软膏治疗轻中度斑块状银屑病的随机自身对照研究

【摘要】 目的 评价0.05%丙酸氟替卡松乳膏单独应用及与0.005%卡泊三醇软膏联合应用治疗轻中度斑块状银屑病的短期疗效和安全性。方法 2020年10月至2021年1月,于北京友谊医院对30例轻中度斑块状银屑病患者采用随机、开放、自身对照临床研究,一侧肢体皮损处早上外用0.005%卡泊三醇软膏、晚上外用0.05%丙酸氟替卡松乳膏（联合用药组）,对侧肢体皮损处每日外用2次0.05%丙酸氟替卡松乳膏（丙酸氟替卡松组）,疗程4周。分别于治疗前、治疗1、2、4周随访,采集静态临床医生整体评估（sPGA）、银屑病面积和严重程度指数（PASI）等临床指标,并记录不良事件。采用重复测量的方差分析、多变量方差分析、Mann-Whitney U秩和检验和独立样本t检验进行疗效和安全性评价。结果 治疗前,两组sPGA评分、PASI评分差异均无统计学意义（均P > 0.05）。治疗1周,丙酸氟替卡松组sPGA（1.10 ± 0.31）分、PASI评分（1.05 ± 0.51）分显著低于联合用药组［sPGA（1.73 ± 0.45）分,PASI评分（1.38 ± 0.69）分,F = 40.74、4.38,均P < 0.05］;治疗2、4周,联合用药组sPGA为（0.83 ± 0.46）、（0.23 ± 0.43）分,PASI评分为（0.53 ± 0.47）、（0.23 ± 0.50）分,均显著低于丙酸氟替卡松组（F = 4.88、56.14、15.21、26.36,均P < 0.05）。治疗1周,丙酸氟替卡松组浸润/肥厚严重程度评分显著低于联合用药组（U = 165.00,P < 0.05）;治疗2、4周,联合用药组红斑、鳞屑严重程度评分均显著低于丙酸氟替卡松组（U = 540.00、765.00、825.00、795.00,均P < 0.05）。结论 单用0.05%丙酸氟替卡松乳膏治疗银屑病起效快,0.05%丙酸氟替卡松乳膏与0.005%卡泊三醇软膏联合用药治疗2、4周效果更好,两种方法安全性均可。     

Topical calcipotriol plus oral fumaric acid is more effective and faster acting than oral fumaric acid monotherapy in the treatment of severe chronic plaque psoriasis vulgaris

BACKGROUND: Calcipotriol is an established topical therapy for psoriasis vulgaris. OBJECTIVE: This study aimed to investigate whether the addition of calcipotriol to fumaric acid ester (FAE) monotherapy had an additive efficacy and an FAE-sparing effect in patients with severe plaque psoriasis. METHODS: This multicentre, randomised, double-blind, vehicle-controlled study included 143 patients for up to 13 weeks treatment. Group A received FAE tablets (Fumaderm) with an increasing daily dosage from 105 to 1,075 mg + ointment vehicle. Group B received FAE tablets + calcipotriol ointment (50 microg/g). Ointments were applied twice daily. Clinical response was assessed using percentage changes in the Psoriasis Area and Severity Index (PASI), from baseline to treatment end. RESULTS: The mean percentage change in the PASI was -76.1% in group B and -51.9% in group A, the difference between treatments was -24.2% (95% CI from -34.2 to -14.2%; p < 0.001). Group B responded more rapidly to treatment. Investigators' and patients' overall efficacy assessments were significantly more favourable for group B (p < or = 0.001). Group B was prescribed less FAE than group A. This difference was greatest at the last visit (mean daily dose 529 and 685 mg, respectively; p = 0.006). Overall adverse events in the two groups were similar. CONCLUSION: This study shows that the combination of calcipotriol and FAEs is significantly more effective and faster acting than FAE monotherapy in the treatment of severe plaque psoriasis. The combination has a slight FEA-sparing effect and therefore a superior benefit/risk ratio.     

Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study

The efficacy, safety and tolerability of calcipotriol cream was compared with betamethasone 17-valerate cream in the treatment of plaque-type psoriasis in a multicentre double-blind, parallel group study. Patients with stable mild-to-moderate chronic disease were randomized to treatment with either calcipotriol, 50 μg/g, in a cream formulation (210 patients) or betamethasone 17-valerate cream, 1 mg/g (211 patients). After a wash-out period of 2 weeks. the treatment was applied twice daily, without occlusion. for 8 weeks or to complete clearing. The severity of psoriasis was assessed using the PASI at baseline and after 4 and 8 weeks treatment. The mean percentage reduction of PASI from baseline to end of treatment was 47.8% in the calcipotriol group and 45.4% in the betamethasone group. The reduction from baseline was highly significant in both groups. but the differecnce between the groups was not significant. There was a difference in the reduction in thickness of the lesions in favour of calcipotriol. The investigator's as well as the patient's overall assessment of treatment response at end of treatment showed no difference between the two treatment groups. Treatment-related adverse events were more frequent with calcipotriol thanbetamethasone. Lesional/perilesional irritation was reported in 16% and 9% (P=0.03). and facial irritation in 10% and 0.5% (P<0.001), respectively. No change was found in serum levels of calcium. Calcipotriol in a cream formulation was effective, safe well-tolerated. and equal in effect to betamethasone valerate cream.     

Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria

Fifty patients with chronic idiopathic urticaria were studied to compare responses to treatment with doxepin (10 mg three times a day) and with diphenhydramine (25 mg three times a day). All patients had an evaluation that failed to disclose a cause for their disease. Therapeutic response was assessed according to the suppression of symptoms and symptom diary scores of daily itching and frequency, number, size, and duration of hives. Total clearing of the pruritus and urticarial lesions occurred in 43% of the patients while receiving doxepin and in only 5% while receiving diphenhydramine (p less than 0.001). Partial or total control of the pruritus and hives was noted in 74% of the patients receiving doxepin and in only 10% of those receiving diphenhydramine (p less than 0.001). Doxepin induced markedly less sedation (22%) than diphenhydramine (46%) (p less than 0.05). Dermatopathologic categories included (1) urticaria simplex, (2) lymphocytic urticaria, and (3) leukocytoclastic urticaria. Patients with urticaria simplex had a more favorable response to doxepin than the two other groups.