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)     

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.     

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.     

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.     

Clinical experience with topical calcitriol (1,25-dihydroxy-vitamin D3) in psoriasis

The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 μg g⁻¹ ointment (Silkis ointment®, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short-contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8-week period; however, the combination had a radiation dose-sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice-daily betamethasone, thereby achieving a corticosteroid-sparing effect. Finally, two studies confirm that calcitriol 3 μg g⁻¹ ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound.     

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized,double-blind,vehicle-controlled clinical trial

BACKGROUND: Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. OBJECTIVES: The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. METHODS: This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. RESULTS: There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle). CONCLUSIONS: No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.     

The efficacy, safety and tolerance of calcitriol 3 microg/g ointment in the treatment of plaque psoriasis: a comparison with short-contact dithranol

OBJECTIVE: A comparison of efficacy, safety and tolerance of a twice-daily application of calcitriol 3 microg/g ointment with dithranol cream. METHODS: The study was an 8-week, prospective, randomised, open, parallel-group trial with 114 patients. Subjects received either 3 microg/g calcitriol ointment (twice daily) or 0. 25-2% dithranol cream (once daily for 30 min). Results were measured using global improvement, global severity, PASI, quality of life (QOL) and Psoriasis Disability Index scores. Safety was determined from reports of adverse events and blood chemistry analysis. RESULTS: At final assessment, calcitriol and dithranol were comparably efficacious. Skin irritation was reported by 5% of calcitriol and 72% of dithranol patients. Patients rated QOL and overall acceptability of calcitriol more highly. CONCLUSIONS: Twice-daily calcitriol ointment (3 microg/g) is equally effective as a once-daily, short-contact dithranol regimen. However, calcitriol is better tolerated than dithranol, and provides a better QOL and a greater patient acceptability.     

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone,narrowband ultraviolet B phototherapy alone,combination of calcipotriol and narrowband ultraviolet B phototherapy once a week,and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.     

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.     

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.     

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.     

Calcitriol vs. dithranol in combination with narrow-band ultraviolet B (311 nm) in psoriasis

BACKGROUND: Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. OBJECTIVES: To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. METHODS: Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. RESULTS: Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. CONCLUSIONS: Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed.     

Combining lesional short-contact dithranol therapy of psoriasis with a potent topical corticosteroid

BACKGROUND: Since its introduction, the effectiveness of dithranol in treating psoriasis has been unequalled by other topical treatments. Out-patient short-contact dithranol treatment is effective with regard to clinical response rate and relapse rate after 1 year. A drawback, however, is the relatively long treatment duration. OBJECTIVES: To study a dithranol regimen combined with a potent topical corticosteroid with regard to clinical response rate, treatment duration and remission period after clearance. METHODS: Twelve patients with stable psoriasis vulgaris participated in this study. We treated three comparable psoriasis lesions on the extremities for 39 consecutive days. The first lesion was treated daily with short-contact dithranol cream followed by clobetasol-17-propionate ointment 5 days per week. The second lesion was treated daily with short-contact dithranol cream followed by the vehicle of clobetasol-17-propionate ointment. The third lesion was treated with clobetasol-17-propionate ointment 5 days per week. The patients attended on days 1, 4, 9, 12, 15, 18, 22, 25, 32 and 39 during treatment. We assessed lesional severity scores at each visit and registered the baseline area at the first visit. During the follow up at weeks 2, 4, 6, 10, 14, 19 and 23 we assessed lesional sum scores. We also estimated the area involved in recurrence of the lesion as a percentage of the baseline area. The overall differences between the three treatment curves for the treatment period and follow-up period separately were tested with a likelihood ratio test. RESULTS: Differences between the curves of the sum scores during treatment (P < 0.001) were mainly due to the different time-course of dithranol monotherapy, which showed a slower decrease in sum score. Differences between the linear trends of the sum score (P < 0.001) and the area score P < 0.001) during follow up were due to a different time-course of the combination therapy, which started lower and increased more slowly, suggesting a slower relapse rate with combination therapy. When comparing the follow-up data, it must be kept in mind that the three treatments showed an overall significantly different sum and area score at the start of follow up. CONCLUSIONS: Intermittent addition of clobetasol-17-propionate ointment enhanced the antipsoriatic efficacy of short-contact, high-dose dithranol therapy in terms of clearing capacity and treatment duration, without shortening remission duration.     

卡泊三醇与氯氟舒松联合外用治疗寻常型银屑病

目的 观察卡泊三醇与氯氟舒松联合分用组，氯氟舒松组及卡泊三醇单用组外用治疗寻常型银屑病的疗效与安全性。方法 患者随机分入三个治疗组，对治疗1，4周后银屑病区严重度指数(PASI)之平均百分变化率进行比较。结果 通过比较显示卡泊三醇与氯氟舒松联合分用组治疗1，4周后的PASI平均百分变化率(PASI改善率)显著高于氯氟舒松组及卡泊三醇单用组，且副反应少于单纯卡泊三醇组。结论 卡泊三醇与氯氟舒松联合外用治疗寻常型银屑病优于卡泊三醇或氯氟舒松单用疗法。     

Safety and efficacy of combined high-dose treatment with calcipotriol ointment and solution in patients with psoriasis

Background: In the vast majority of psoriatic patients, psoriatic lesions are localised on the body as well as on the scalp. Therefore, safety data on the combined use of calcipotriol in lotion and calcipotriol in ointment are needed. Objective: This study investigated the effect of high-dose treatment with a combination of calcipotriol ointment and scalp solution on calcium metabolism, indices of bone turnover and PASI in patients with extensive psoriasis. Methods: Following a 2-week wash-out period, 88 patients were randomised to 4 weeks of treatment with either calcipotriol ointment/scalp solution (80-100 g/week and 30-50 ml/week, respectively; n = 41) or with a dithranol/tar regimen (n = 47). Patients were seen at weeks 1, 2 and 4 during treatment and 1 week following cessation of treatment. Results: No significant differences at the end of treatment were found between the 2 groups with respect to 24-hour urinary excretion of calcium (expressed as calcium/creatinine ratio), phosphate or pyridinoline, serum concentrations of calcium (albumin corrected), creatinine, phosphate, parathyroid hormone, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), osteocalcin, alkaline phosphatase (total and bone-specific iso-enzymes) or 1-collagen telopeptide. At the end of treatment, the psoriasis area and severity index had decreased by 57.4% in the calcipotriol group and by 36.1% in the dithranol/tar group (p = 0.004). Investigators' and patients' assessments of overall efficacy also favoured treatment with calcipotriol (p < 0.001). Conclusion: The combined use of calcipotriol ointment/scalp solution did not affect the indices of calcium metabolism or bone turnover and was significantly more effective than dithranol/tar in reducing disease severity and extent in patients with extensive psoriasis.     

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.     

钙泊三醇倍他米松软膏外用治疗寻常性银屑病的随机、双盲、对照研究

目的 探讨钙泊三醇倍他米松软膏外用治疗稳定期寻常性银屑病患者的临床疗效和安全性。方法 随机、双盲、阳性药物平行对照、多中心临床试验,入组320例寻常性银屑病患者,随机纳入试验组或对照组,疗程4周。试验组早晨外用模拟剂软膏基质,晚间外用钙泊三醇倍他米松软膏;对照组早晚单用卡泊三醇软膏。于首次用药后第1、2、4周观察临床疗效及安全性。结果 治疗4周后试验组PASI评分较基线下降百分比（79.23%）大于对照组（70.43%）,两组比较,P < 0.01;且在治疗1周后的疗效优于对照组。治疗4周后,PASI评分较基线下降≥75%的患者频数百分比比较,试验组有效率为73.03%,对照组为48.32%,P < 0.01,两组差异有统计学意义。治疗1、2、4周后试验组靶皮损红斑、浸润、鳞屑单独积分以及皮损总面积百分比等指标改善方面均优于对照组。320例受试者中不良事件发生率为18.1%,不良反应发生率为13.1%,两组间差异无统计学意义。药物不良反应主要为与皮肤有关的轻中度反应如瘙痒、毛囊炎、红斑等。结论 钙泊三醇倍他米松软膏治疗稳定期寻常性银屑病患者具有起效快、疗效好和用药方便、相对安全的特点。     

Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis

For psoriasis therapy, topical derivatives of vitamin D3 represent a versatile option: they can be used either alone or in combination with other agents such as topical corticosteroids. In this two-phase parallel-group study, the naturally occurring vitamin D3 analogue, calcitriol, was compared with the vitamin D analogue calcipotriol in 125 patients with chronic plaque-type psoriasis. The proposed treatment regimen was an initial bitherapy for 2 or 4 weeks, with clobetasol propionate 0.05% cream, a super potent topical corticosteroid applied in the morning and either calcitriol 3 mug/g ointment or calcipotriol 50 mug/g ointment applied in the evening, followed by monotherapy with either calcitriol or calcipotriol applied twice daily until endpoint week 12. Efficacy evaluations (global assessment of improvement, PASI and body surface area (BSA) affected) showed no significant differences between the two regimen groups at the primary endpoints (week 2 and week 12) or at any interim points. At week 2 the investigator's global assessment showed clinical success (psoriasis markedly improved, almost clear or clear) for more than 50% of the patients in both groups and for 48 (79%) and 56 (88%) patients, respectively in the calcitriol and calcipotriol regimen group at week 12. Least-square means analysis of PASI indicated the calcitriol regimen to be equivalent to the calcipotriol regimen. There were no significant differences between the two groups with regards to cutaneous safety or to incidence of adverse events. The present study shows that for the treatment of mild to moderate plaque psoriasis calcitriol 3 mug/g ointment can provide a safe and effective alternative to calcipotriol 50 mug/g ointment while being administered within a regimen based on a bitherapy with corticosteroids followed by a vitamin D3 maintenance monotherapy.     

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.