Patient attitudes to topical antipsoriatic treatment with calcipotriol and dithranol

OBJECTIVE: Assessment of patient preference for antipsoriatic treatment with calcipotriol ointment or short-contact dithranol cream. METHODS: Two hundred and fifty-eight psoriatic patients treated with calcipotriol (n = 138) or dithranol (n = 120) for up to 3 months, assessed the acceptability of treatment, overall satisfaction with treatment, their treatment preference using the 'willingness to pay' principle and selected their treatment of choice. RESULTS: Overall satisfaction with calcipotriol was significantly better (72.7%, dithranol 60.3%; odds ratio 1.75, 95% CI 1.03, 2.99: P = 0.04). Patients considered calcipotriol a more acceptable treatment than dithranol in its appearance, smell, non-irritancy, method and ease of application and lack of staining. Dithranol was considered less sticky than calcipotriol. Patients were 'willing to pay' a mean of pound sterling 12.16 monthly for calcipotriol and pound sterling 10.66 monthly for dithranol. 'Willingness to pay' did not correlate well with overall treatment satisfaction and was not correlated with household income. Calcipotriol was the preferred treatment of choice (calcipotriol 63%, dithranol 24%). CONCLUSION: Patients with psoriasis prefer treatment with calcipotriol ointment over short-contact dithranol cream.     

Calcipotriol plus short-contact dithranol: a novel topical combination therapy for chronic plaque psoriasis

The purpose of this double-blind randomised parallel-group study was to compare the efficacy and safety of short-contact treatment with dithranol ointment (2%) with its combination with calcipotriol ointment (50 microg/g) in 2 groups of in-patients with chronic plaque psoriasis. The patients of the first group (n = 23) topically applied dithranol once daily for 30 min and the vehicle of calcipotriol twice daily. The patients of the second group (n = 23) used a single topical application of dithranol for 30 min daily and additionally applied calcipotriol twice daily. The extent and the severity of psoriasis were assessed by means of psoriasis area and severity index score (PASI score) before the onset of the 6-week therapy and weekly thereafter. The difference between the two groups with regard to the mean PASI score became statistically significant already after the first week of treatment and remained so until the end of the trial. No significant differences were observed between the two groups with respect to the cutaneous adverse events. These findings indicate that the addition of calcipotriol ointment to short-contact dithranol markedly augments the therapeutic efficacy of the latter in chronic plaque psoriasis and impressively accelerates the response of psoriatic plaques to this well-tolerated regimen.     

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting

BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.     

Long-term treatment of psoriasis with calcipotriol scalp solution and cream

The efficacy and safety of long-term concurrent twice-daily treatment of scalp and body psoriasis with calcipotriol scalp solution (50 mcg/ml) and calcipotriol cream (50 mcg/g) were evaluated in a prospective, multi-centre, open-label, non-controlled evaluation over 52 weeks in 202 patients. Safety and efficacy as measured by total sign score (scalp psoriasis), modified PASI (body psoriasis) and patient self-assessment were assessed at week 2, 6 and 10 and thereafter every six weeks. By week 28, mean total sign score for scalp psoriasis had reduced from 5.9 to 2.5 (p<0.001). No further reduction was seen. By week 34, mean PASI for body psoriasis had reduced from 6.8 to 2.6 (p<0.001). No further reduction was seen. At week 52, the percentage of patients assessing their psoriasis as moderate or severe had decreased from 72 to 21% for scalp psoriasis and from 62 to 19% for body psoriasis. Facial irritation was the most frequent adverse event (91/276 events) with the highest incidence occurring at week 2 and few new reports at subsequent visits. There were no significant changes in mean serum calcium, parathormone or urinary calcium/creatinine ratio. Combined treatment with calcipotriol scalp solution and cream was effective and safe for long-term treatment of scalp and body psoriasis.     

Calcipotriol Ointment

Abstract

Calcipotriol, a vitamin D₃ analog, acts not only to inhibit cell proliferation and enhance cell differentiation in the skin of patients with psoriasis, but also appears to have effects on immunologic markers that are thought to play a role in the etiology of the disease. In several well designed, short term studies in adults, calcipotriol ointment 50 μg/g twice daily provided similar or superior efficacy to several other antipsoriatic agents in adult patients with mild to moderate psoriasis. In patients with nonscalp psoriasis, the drug provided superior efficacy to twice daily placebo (vehicle ointment), twice daily fluocinonide 500 μg/g, once daily tacalcitol 4 μg/g and twice daily coal tar 5% plus allantoin 2% and hydrocortisone 0.5%. Furthermore, calcipotriol therapy generally provided superior efficacy to twice daily betamethasone valerate 1 to 1.2 mg/g or once daily dithranol 1 to 20 mg/g, and similar efficacy to twice daily betamethasone dipropionate plus salicylic acid or once daily maxacalcitol 6 to 50 μg/g. Limited data indicated that calcipotriol ointment 50 μg/g also improved overall disease severity in children. In combination with other antipsoriatic agents [acitretin, cyclosporine, betamethasone valerate, halobetasol (ulobetasol)], ultraviolet B or psoralen ultraviolet A (PUVA) phototherapy, calcipotriol ointment 50 μg/g twice daily improved the beneficial effects of these drugs on overall disease severity in adult patients with moderate to severe psoriasis. Furthermore, in separate trials, calcipotriol combination therapy reduced the dosage of acitretin required to achieve clearance of psoriasis and the duration of PUVA and dosage of UVA phototherapy, potentially improving the benefit/risk ratio for these other antipsoriatic treatments. Calcipotriol was generally well tolerated in short and long term studies in adult patients, with the majority of adverse events being mild to moderate in intensity and transient. The most common adverse events associated with calcipotriol therapy were dermatologic in nature and included lesional or perilesional irritations, face and scalp irritations, worsening of psoriasis and miscellaneous dermatologic events. Notably, there have been very few reports of patients developing hypercalcemia or hypercalciuria during calcipotriol therapy, with most occurring in patients who exceeded the recommended dosage of 100 g/week. Although data in children are limited, the drug was well tolerated with the nature and incidence of adverse effects similar to those observed in adult patients. Conclusions: Extensive clinical experience, along with several short and long term clinical trials, has shown calcipotriol ointment to be an effective and well tolerated topical agent in adult patients with psoriasis. In addition, calcipotriol ointment proved beneficial in combination with other topical, phototherapy or systemic antipsoriatic treatments, reducing the dosage and/or duration of some of these treatments and potentially improving their benefit/risk ratio. Calcipotriol ointment is valuable as a first- or second-line therapy option for the management of mild to moderate psoriasis and in combination with other antipsoriatic agents for more severe psoriasis.

Pharmacologic Properties

Calcipotriol inhibits cell proliferation and enhances cell differentiation in the skin of patients with psoriasis. These effects are mediated by binding of the drug to vitamin D receptors. Flow cytometric analysis of epidermal samples has shown significant decreases relative to placebo in numbers of proliferating basal keratinocytes in psoriatic skin treated with topical calcitriol. In addition, application of calcipotriol ointment 50 μg/g twice daily for up to 8 weeks has been shown to result in partial recovery of the stratum corneum, restoration of the stratum granulosum, and correction of intercellular spacing and number and structure of desmosomes. Application of calcipotriol ointment for 4 weeks has been associated with suppression of epidermal T cell and polymorphonuclear leucocyte accumulation in psoriatic lesions. The drug has also been shown to reduce numbers and activity of Langerhans cells, although these effects have not been shown consistently across studies and require further investigation. Other effects described include increased interleukin-10 and reduced interleukin- 8 expression, and normalization of cellular integrin distribution. Overall, application of up to 120 g/week of calcipotriol ointment 50 μg/g did not alter calcium utilization or bone turnover in pharmacodynamic studies in humans. Dosages of 100 to 300 g/week have, however, been associated with increased levels of calcium and reduced levels of parathyroid hormone (PTH) in serum, and increased urinary excretion of calcium. These effects have been attributed to increased intestinal absorption of calcium and subsequent suppression of secretion of PTH and endogenous calcitriol. Measurement of levels of radioactivity in blood, urine and feces after application of ointment containing ³H-calcipotriol has indicated systemic absorption of up to approximately 6% of applied drug in patients with psoriasis. Calcipotriol appears to be metabolized and cleared rapidly after absorption, with hepatic oxidation to 2 relatively inactive metabolites (MC1046 and MC1080) being the major route of elimination. Data obtained in rats showed elimination half-lives in blood collected up to 10 minutes after intravenous administration to be 4 and 14 minutes for calcipotriol and calcitriol, respectively. Corresponding total clearance values were 0.68 and 0.0055 L/h.

Clinical Efficacy

The short term clinical efficacy of calcipotriol ointment 50 μg/g twice daily has been evaluated in several reasonably sized (≥50 enrolled patients) comparative studies of ≤14 weeks duration in adult patients with psoriasis. In placebo (vehicle)-controlled studies, calcipotriol recipients experienced better reductions in overall disease severity (52 to 59% vs 16 to 35%), with a greater percentage of calcipotriol-treated patients achieving a ≥75% improvement in severity of psoriasis or complete clearance (responders) than placebo (59 to 74% vs 12 to 19%). Furthermore, topical calcipotriol ointment 50 μg/g twice daily provided superior efficacy to once daily tacalcitol 4 μg/g, twice daily fluocinonide 500 μg/g or twice daily coal tar 5% plus allantoin 2% and hydrocortisone 0.5% in patients with nonscalp psoriasis. In addition, calcipotriol recipients generally experienced superior beneficial effects on psoriasis severity to betamethasone valerate (1 to 1.2 mg/g twice daily) or once daily dithranol 1 to 20 mg/g recipients and similar efficacy to those receiving betamethasone dipropionate plus salicylic acid or once daily maxacalcitol 6 to 50 μg/g. Calcipotriol ointment also had significantly (p < 0.001) greater cosmetic acceptability than short-contact dithranol cream. Patient’s quality of life was significantly (p ≤ 0.02, both comparisons) improved from pretreatment levels with twice daily calcipotriol ointment 50 μg/g (assessed using Psoriasis Disease Index and Sickness Impact Profile instruments). Long term evaluations indicated that improvements in disease severity demonstrated with calcipotriol ointment therapy in the short term were maintained throughout the study period in several noncomparative trials of up to 1 year in duration in adult patients with psoriasis. At the end of the treatment period, 54 to 98% of calcipotriol recipients had shown a marked or ≥75% improvement in severity of psoriasis in these trials. Furthermore, in a randomized double-blind study, significantly (p < 0.05) more recipients of combination ‘pulse therapy’ consisting of calcipotriol ointment 50 μg/g (applied twice daily on week days) plus halobetasol ointment 500 μg/g (applied twice daily during the weekend) remained in remission throughout the 6-month study period than halobetasol recipients (using the same dosage plus placebo ointment twice daily during the week) [76 vs 40%]. Combining topical calcipotriol ointment (50 μg/g) with a topical corticosteroid, ultraviolet B (UVB) phototherapy, psoralen ultraviolet A (PUVA) phototherapy, or systemic (cyclosporine, acitretin) antipsoriatic agents improved the effects of the individual agents in reducing overall disease severity in short term studies of 2 to 12 weeks’ duration in adults. Overall psoriasis severity scores were reduced by 74 to 91% with calcipotriol-combination therapy compared with reductions of 35 to 83% in comparator agent monotherapy groups. Importantly, the addition of calcipotriol to acitretin or PUVA phototherapy reduced the dosage of these antipsoriatic therapies required and duration of UVA phototherapy. Data on the therapeutic efficacy of topical calcipotriol ointment in children are limited. After 8 weeks’ therapy, there was no significant difference in the reduction in overall disease severity between twice daily calcipotriol ointment 50 μg/g and placebo (ointment vehicle; 52 vs 37% reduction) in children aged 2 to 14 years. Nevertheless, subscale scores for erythema and scaling showed significantly (p < 0.05, both comparisons) greater reductions in calcipotriol than placebo recipients. In addition, significantly (p < 0.05) more calcipotriol recipients had shown a marked improvement or clearance of psoriasis than placebo (60 vs 44%). Topical calcipotriol ointment 50 μg/g twice daily also proved effective in reducing disease severity in a long term noncomparative study in 12 children aged 8 to 15 years. The mean overall Psoriasis Area and Severity Index score was reduced by 65% following calcipotriol treatment for a mean duration of 40 weeks.

Tolerability

In short term studies (6 to 8 weeks’ duration) the most common dermatologic adverse events associated with calcipotriol ointment 50 μg/g twice daily were lesional and perilesional irritation (12 to 20.1% of patients), face and scalp irritations (2 to 4.2%), worsening of psoriasis (2.9 to 3.9%) and miscellaneous adverse events (2.2 to 10.9%). The incidence of nondermatologic adverse events (e.g. arthralgias, bronchospasm, fatigue, flu-like symptoms, headache and nausea/vomiting) in these large trials was 1.2 to 2.9% of patients, with the overall incidence of adverse events ranging from 12 to 35.1% of patients. Symptoms were generally transient and mild to moderate in intensity. Zero to 10.2% of patients withdrew because of adverse events attributable to calcipotriol ointment treatment. The nature of adverse events occurring in long term studies was similar to those observed with short term studies, although the overall incidence of adverse events declined over time. Serious adverse events associated with calcipotriol therapy were rare. Calcipotriol ointment 50 μg/g twice daily was better tolerated than dithranol, but was associated with a significantly (p < 0.001) higher incidence of lesional and perilesional irritation than betamethasone valerate treatment. Although no significant differences in the nature and incidence of adverse events were reported between calcipotriol ointment or tacalcitol treatment in patients with nonscalp psoriasis, in those with scalp psoriasis there was a trend to a higher incidence of facial irritations with calcipotriol than tacalcitol. In general clinical practice, there have been very few reports of patients developing hypercalcemia or hypercalciuria during calcipotriol therapy, with most occurring in patients who exceeded the recommended dosage of 100 g/week. All episodes of hypercalcemia or hypercalciuria have resolved on discontinuation of treatment. Furthermore, there were no reports of any significant abnormalities in hematologic and biochemical laboratory parameters with twice daily calcipotriol ointment 50 μg/g in clinical trials. Limited data from short term studies of 8 weeks’ duration indicated that calcipotriol ointment 50 μg/g twice daily was well tolerated in 99 children aged 2 to 15 years. No serious adverse events were reported. Adverse events were similar to those observed in adults. In a short term study, adverse events possibly or probably related to calcipotriol therapy were lesional and perilesional irritations (11 to 16% of patients), irritations of the face and/or scalp (5 to 6%), various skin rashes (6%) and worsening of psoriasis (2%). In addition, there were no significant changes in hematologic or biochemical laboratory parameters, including no clinically relevant changes in liver and renal function tests or serum calcium levels. Although data are very limited, a study in 12 children (aged 8 to 15 years) indicated that calcipotriol ointment 50 μg/g twice daily (for up to 106 weeks; mean duration of therapy was 40 weeks) was well tolerated with no serious adverse effects reported.

Dosage and Administration

Calcipotriol ointment 50 μg/g is approved for the treatment of moderate plaque psoriasis. It should be applied once or twice daily to the affected area up to a maximum of 100 g/week in adult patients. In Japan, the maximum recommended adult dosage is 90 g/week. Currently, in the US there are no dosage recommendations available for the use of calcipotriol in children, whereas in the UK the maximum recommended dosage in children aged 6 to 12 years is 50 g/week increasing to 75 g/week in those over 12 years of age; no dosage recommendations are available for children less than 6 years of age. Calcipotriol should not be applied to the face or eyes, and hands should be washed to prevent this happening inadvertently. Calcipotriol is contraindicated in patients with known calcium metabolism disorders, evidence of vitamin D toxicity or hypersensitivity to calcipotriol or any other constituents of the ointment. The use of the drug during pregnancy is not recommended.     

An Open Label Prospective Randomized Trial to Compare the Efficacy of Coal Tar-Salicylic Acid Ointment Versus Calcipotriol/Betamethasone Dipropionate Ointment in the Treatment of Limited Chronic Plaque Psoriasis

Background:Chronic plaque psoriasis is a common papulosquamous skin disorder, for which a number of topical agents are being used including coal tar, topical steroids and more recently topical calcipotriol/betamethasone dipropionate. There is no study comparing purified coal tar preparation with calcipotriol/betamethasone dipropionate ointment in limited chronic plaque psoriasis.Results:Mean PASI was significantly lower at week 2 (P = 0.01) and week 4 follow-up (P = 0.05) and the mean reduction in PASI was significantly higher at week 2 (P = 0.02) with calcipotriol/betamethasone than coal tar-salicylic acid, but this difference was not sustained at subsequent follow-up visits. Similarly, PGA scores at weeks 2 and 4 were significantly lower with calcipotriol/betamethasone dipropionate ointment (P = 0.003 and P = 0.007 respectively). There was no significant difference in any parameter during subsequent follow-up visits or at the end of the treatment phase (12 weeks).Conclusion:Topical nightly application of calcipotriol/betamethasone dipropionate ointment leads to an initial, more rapid reduction in disease severity, but the overall outcome parameters are comparable in the two treatment groups.     

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 comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting

BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.     

The potential of the essential fatty acid-deficient hairless rat as a psoriasis screening model for topical anti-proliferative drugs

The objective of this study was to establish essential fatty acid deficiency (EFAD) in hairless rats and investigate the potential of this model as a psoriasis screening model by testing the effects of calcipotriol and dithranol on differentiation and proliferation in the epidermis. Hairless rats were fed with a fat-free diet lacking linoleic acid. The EFAD condition was established within 8 weeks. In order to ensure that this condition had been established, several parameters were measured and observed, i.e. animal weight, water consumption, transepidermal water loss, clinical skin symptoms, histology of the epidermis and fatty acid analysis of serum and skin. Immediately after the EFAD condition had been established, the animals were treated with dithranol ointment or different concentrations of calcipotriol solution. A reduction in epidermal thickness of 15-20% was seen after the treatment with calcipotriol. Dithranol and its coal tar-containing vehicle also showed a reductive effect on epidermal thickness. EFAD hairless rats possess various histological changes resembling psoriasis. These histological changes normalise during treatment with anti-psoriatic drugs as calcipotriol, dithranol and coal tar. The results of the present study indicate that the EFAD rat may be a useful model for studies of anti-psoriatic drugs affecting cell proliferation.     

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.)     

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.     

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

We studied the effects of combining topical calcipotriol, used at the maximal licensed dose, and narrow-band short wave ultraviolet light (TL01) on systemic calcium homeostasis in the treatment of chronic plaque psoriasis. Patients were randomized in an open fashion to receive either UVB alone, UVB plus 100 g of calcipotriol (50 μg/g) ointment per week or calcipotriol ointment alone (100 g/week). With the exception of a slight increase in serum phosphate in the group receiving combination therapy (from 0·92 to 1·22 mmol/l; P= 0·046), no differences were observed between or within the groups. Psoriasis area and severity scores (PASI) improved to a greater extent in those patients receiving both UVB and calcipotriol (P= 0·045). The combination of UVB and calcipotriol is a safe, effective treatment for chronic plaque psoriasis.     

Once daily treatment of psoriasis with tacalcitol compared with twice daily treatment with calcipotriol. A double-blind trial

Once daily topical treatment of psoriasis with tacalcitol ointment (4μ/g) was compared with twice daily treatment with calcipotriol ointment (50μg/g) in a double-blind, randomized study over a treatment period of 8 weeks. The severity of pruritus, erythema, infiltration and scaling was scored on a scale from 0 to 4. These features were scored at the initiation of treatment, after 2,4,6 and 8 weeks of treatment, and at 4 weeks after discontinuation of treatment. The sum score was the total score for erythema, infiltration and scaling. Serum levels of calcium, phosphate, ionized calcium and intact parathyroid hormone were used as safety parameters. Two hundred and eighty-seven adults with stable plaque psoriasis participated and were treated at least once. Both tacalcitol and calcipotriol ointments effectively reduced the severity of psoriasis. The mean reduction in the sum score in the intention-to-treat population of 287 patients was 4.03 in the group treated with tacalcitol compared with 5.05 in the group treated with calcipotriol. The mean baseline sum scores were 7.64 and 7.45, respectively. The acceptability of both ointments was excellent, and none of the patients had adverse effects in terms of increased serum calcium or other alterations in calcium metabolism. Although less effective than calcipotriol ointment used twice daily, tacalcitol ointment is an effective and useful once daily treatment of chronic plaque psoriasis.     

Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial

Background Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy. Objectives To compare the efficacy and safety of once‐daily treatment with a combination of calcipotriol 50 μg g^?1 plus betamethasone 0·5 mg g^?1 (as dipropionate) (Xamiol^®; LEO Pharma A/S, Ballerup, Denmark) and twice‐daily calcipotriol 50 μg mL^?1 scalp solution in patients with scalp psoriasis. Methods This 8‐week, multicentre, randomized, investigator‐blind, parallel‐group study compared two‐compound calcipotriol/betamethasone scalp formulation with calcipotriol scalp solution in patients with moderately severe scalp psoriasis. Primary efficacy outcome was the proportion of patients who achieved ‘clear’ or ‘minimal’ disease severity according to investigator’s global assessment of disease severity at week 8. Secondary efficacy outcomes and adverse events were also evaluated. Relapse and rebound were assessed in an 8‐week, post‐treatment observation phase. Results In total, 207 patients received the two‐compound scalp formulation and 105 patients received calcipotriol scalp solution. The proportion of patients with ‘clear’ or ‘minimal’ disease at week 8 was significantly greater in the two‐compound scalp formulation group (68·6%) than in the calcipotriol scalp solution group (31·4%; P < 0·001). Improvement was more rapid with the two‐compound scalp formulation than with calcipotriol scalp solution. Further evidence of the superiority of the two‐compound scalp formulation over the scalp solution was demonstrated through greater improvements in clinical signs and fewer adverse events. Conclusions A once‐daily combination of calcipotriol plus betamethasone dipropionate was significantly more effective and better tolerated than twice‐daily calcipotriol scalp solution in the treatment of scalp psoriasis.     

Long-term efficacy and tolerability of topical calcipotriol in psoriasis. Results of an open study.

Calcipotriol is a non-calcaemic vitamin D3 analogue. In short-term studies, topically applied calcipotriol is both efficacious and safe for the treatment of psoriasis vulgaris. The purpose of the present study was to determine the efficacy and safety of calcipotriol ointment in patients treated for approximately 6 months. Fifteen patients with plaque-type psoriasis were treated daily with calcipotriol ointment 50 micrograms/g. After treatment for 6 weeks there was a significant alleviation of erythema, infiltration and scaling. This degree of improvement was maintained throughout the study, except in one patient, who was withdrawn at week 15 because of minimal improvement. At the end of treatment, 80% of the patients showed a moderate improvement at least. Local adverse events occurred in 3 patients. These were mild and transient. Hypercalcaemia or other laboratory abnormalities did not develop in any patient. Morphometric examination of biopsies taken from perilesional skin (i.e. skin exposed to calcipotriol) at the end of treatment did not show signs of epidermal or dermal atrophy compared with uninvolved psoriatic skin. Although only a limited number of patients participated in the study, these results indicate that calcipotriol ointment 50 mu/g is both efficacious and safe for the long-term treatment of psoriasis.     

Efficacy of treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial

BACKGROUND: A two-compound product containing calcipotriol 50 microg/g and betamethasone dipropionate 0.5 mg/g (Daivobet, Dovobet) has been demonstrated to be an effective, once daily, treatment for psoriasis vulgaris. OBJECTIVE: To compare the efficacy and safety of treatment with the two-compound product for 4 weeks followed by calcipotriol for 4 weeks, with that of tacalcitol for 8 weeks in patients with stable psoriasis vulgaris. METHODS: 501 patients were randomised to double-blind treatment with the two-compound product followed by calcipotriol 50 microg/g once daily, or to tacalcitol 4 microg/g once daily. RESULTS: Treatment with the two-compound product/calcipotriol was significantly more effective than tacalcitol in terms of mean percentage PASI reduction (65.0 vs. 33.3% at week 4 and 59.0 vs. 38.4% at week 8; p < 0.001 for both). CONCLUSION: A treatment regimen comprising calcipotriol/betamethasone ointment (Daivobet) for 4 weeks followed by calcipotriol for 4 weeks is superior to tacalcitol ointment for 8 weeks in patients with psoriasis vulgaris.     

Calcipotriol versus coal tar: a prospective randomized study in stable plaque psoriasis

BACKGROUND: Topical therapies are the first line of treatment for patients with stable plaque psoriasis (SPP) affecting a limited body surface area. Very few trials comparing newer agents, such as 0.005% topical calcipotriol, with conventional modes of therapy, such as coal tar ointment, have been reported. METHODS: A prospective, right-left randomized, investigator-blinded study with a 12-week treatment period and an 8-week follow-up period was performed. Thirty-six patients with nearly bilaterally symmetrical SPP lesions on the limbs were instructed to apply 5% coal tar ointment overnight on one side once daily and 0.005% calcipotriol ointment on the other side twice a day. All patients were advised to expose both sides to the sun for 2 h every day. Psoriatic lesions and progress during treatment were evaluated using the severity (0-3) scale of erythema, scaling and induration (ESI score). Evaluation was carried out every 2 weeks during the treatment period and monthly during follow-up. At the end of 12 weeks, patients with > 75% reduction in the ESI score were considered to be markedly improved, those with 51-75% reduction to be moderately improved, those with 26-50% reduction to be minimally improved and those with < 25% to be non-responders. Self-assessment by the patients regarding the efficacy and acceptability of the two modalities was on a five-point scale. Serum calcium, serum phosphate, total and differential serum proteins, 24-h urinary calcium and phosphate were monitored both at baseline and after completion of therapy. RESULTS: Thirty of the 36 recruited patients completed the study. The difference in clinical response between the two sides was statistically significant at 4, 6 and 8 weeks, with the percentage reduction in ESI score with calcipotriol being 65.7 +/- 12.2% compared with 45.8 +/- 16.6% with coal tar at 8 weeks (P < 0.01, t = 6.4). However, the difference in clinical response at 10 and 12 weeks between the two sides was not significant, with a mean reduction of 71.9 +/- 13.3% in ESI score on the calcipotriol-treated side compared with 69.4 +/- 15.4% with coal tar ointment (P > 0.05). In the follow-up period of 8 weeks, recurrence of lesions was noted in 10% of patients treated with calcipotriol compared with 16.7% in those treated with coal tar after an average period of 6 +/- 1.2 and 5 +/- 1.3 weeks, respectively (P > 0.05). CONCLUSIONS: It was found that 0.005% calcipotriol ointment produced a faster initial response and had better cosmetic acceptability in patients, although after a long period of treatment, i.e. 12 weeks, 5% coal tar ointment had comparable efficacy. There was no statistically significant difference in the relapse rates between the two modalities.     

A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis

In a multicentre, randomized, open study, 306 patients of either sex, over 18 years of age with stable chronic plaque psoriasis > 100 cm² in surface area, and who gave informed consent, applied Dovonex (calcipotriol) ointment (50 μg/g) twice daily or Dithrocream (short-contact dithranol) 0.1–2% for up to 3 months. The number of patients 'cleared' or with 'marked improvement' at the end of treatment were: investigators' assessment—calcipotriol 92 of 153 (60.1%); dithranol 67 of 131 (51.1%); odds ratio 1.44 [95% confidence interval (CI) 0.90, 2.31; P  = 0.128]; patients' assessment—calcipotriol 93 of 153 (60.8%); dithranol 65 of 131 (49.6%); odds ratio 1.57 (95% CI 0.98, 2.52; P  = 0.059). Significant improvement in patients' quality of life as assessed by the Psoriasis Disability Index (PDI) and the Sickness Impact Profile (SIP) were seen in both treatment groups. Reduction in the total mean score for PDI was 6.5 in the calcipotriol group (95% CI 4.4, 8.6; P  = 0.001) and 3.7 in the dithranol group (95% CI 1.1, 6.3; P  = 0.005). The reduction in the total mean score for SIP was 2.8 in the calcipotriol group (95% CI 1.4, 4.3; P  < 0.001) and 1.7 in the dithranol group (95% CI 0.2, 3.1; P  = 0.024). Calcipotriol treatment tended to have advantages over treatment with dithranol in improving quality of life.     

UVA1光疗联合卡泊三醇软膏治疗甲银屑病的临床疗效观察

目的探讨UVA1光疗联合卡泊三醇软膏治疗甲银屑病的临床疗效,进而为甲银屑病患者的治疗提供临床依据。方法将收集的60例寻常型银屑病甲损害的患者随机分为2组,均给予卡泊三醇软膏2次/d,联合治疗组予以UVA1照射(2次/周)治疗,2组治疗方案疗程均为6个月;在治疗前及治疗后,对患者进行银屑病甲严重程度指数(NAPSI)。结果 60例寻常型银屑病甲损害患者中,平均年龄(50.57±16.24)岁,2组在年龄、性别、病程比较差异无统计学意义(P0.05);2组患者病甲治疗前NAPSI评分:联合治疗组:27.07±10.86,卡泊三醇软膏组:25.93±10.73,2组比较差异无统计学意义(t=0.449,P0.05);治疗后2组NAPSI评分分别为:联合治疗组:12.67±7.60,卡泊三醇软膏组:18.10±8.93,NAPSI评分差异有统计学意义(P0.05);治疗后联合治疗组临床痊愈10例,痊愈率33.33%,有效率56.67%,卡泊三醇软膏组临床痊愈0例,痊愈率0%,有效率13.33%,2组有效率的比较有统计学意义(P0.01)。结论UVA1联合卡泊三醇软膏治疗甲银屑病的疗效优于单纯使用卡泊三醇软膏。