Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis.

Vitamin D3 (VD3) analogues-containing ointments are known to occasionally cause hypercalcemia in psoriasis patients, and the frequency of hypercalcemia is suggested to vary based on the VD3 analogue used. In this study, to address the differences in calcemic effects of VD3-containing ointments, the calcemic effects of marketed VD3-containing ointments, including calcipotriol (Cal), maxacalcitol (Max), tacalcitol (Tac), calcipotriol/betamethasone dipropionate (Cal/BDP) and maxacalcitol/betamethasone butyrate propionate (Max/BBP) ointments, were evaluated in a rat model of imiquimod-induced dermatitis. The topical application of Tac, Max and Max/BBP ointments, but not Cal and Cal/BDP ointments, to the imiquimod-induced skin lesions significantly induced an increase in the serum calcium level compared with the vaseline-treated group. Calcemic effect of VD3 analogues in rats treated with VD3-containing ointments was analyzed by evaluating the expression of vitamin D receptor target genes, such as Cyp24a1, Trpv5 and CalbindinD28k, in the intestine and kidney. Real-time reverse transcription PCR (RT-PCR) analysis showed that the renal and intestinal Cyp24a1 expressions in the Cal- and Cal/BDP-treated groups were significantly lower than those in the Tac-, Max- and Max/BBP-treated groups, suggesting that systemic exposure of VD3 analogues in the Cal- and Cal/BDP-treated groups were lower than those in the other ointment-treated groups. In addition, the renal Trpv5 and CalbindinD28k expressions, calcium-transporting genes, were increased in the Max- and Max/BBP-treated groups compared with the Cal- and Cal/BDP-treated groups. Thus, because of the low systemic exposure of VD3 analogues, Cal and Cal/BDP ointments have lower calcemic effect than the other VD3-containing ointments in rats with psoriasis-like dermatitis.

Comparative evaluation of efficacy and safety of calcipotriol versus tacalcitol ointment, both in combination with NBUVB phototherapy in the treatment of stable plaque psoriasis.

BACKGROUND: Vitamin D analogues and NBUVB phototherapy are both well-established modalities of treatment in psoriasis. The objective of this open label, intraindividual, left right study was to compare two different vitamin D analogues, calcipotriol and tacalcitol, in combination with NBUVB phototherapy in chronic stable plaque psoriasis. METHODS: Thirty patients with stable plaque psoriasis were enrolled for a 12-week clinical trial. The target lesion on left side was treated topically with tacalcitol ointment once daily, while that on the right side was treated with calcipotriol ointment twice daily. NBUVB phototherapy was given thrice weekly. Efficacy was assessed by target plaque scoring. RESULTS: Both therapies resulted in statistically significant reduction in erythema, scaling, thickness and target plaque score, seen as early as 2 weeks into therapy. However, calcipotriol combination led to an earlier clearance of plaques and a lesser relapse rate than tacalcitol combination. The number of treatment sessions and cumulative NBUVB doses were significantly lower in the calcipotriol-treated group. CONCLUSION: Both vitamin D analogues appear to be safe, effective and cosmetically acceptable, calcipotriol being more efficacious, well tolerated with a rapid onset of action and a better maintenance of response.

Freckling promoted by topical tacalcitol in a Japanese boy with left eyelid vitiligo.

Vitiligo is an acquired disorder in which the loss of melanocytes results in depigmented patches. Topical tacalcitol, a vitamin D(3) analog, is occasionally used to treat vitiligo. We report a case of a 7-year-old Japanese boy who showed moderate repigmentation and worsened freckles after using topical tacalcitol to treat a vitiligo lesion on and around the left eyelid. Topical tacalcitol might have induced and worsened the freckles, because the changes occurred during treatment. Dermatologists should be aware that topical application of tacalcitol to the cheeks can cause freckling and worsen existing freckles, in predisposed children, as described here.

Randomized, double-blind clinical trial to evaluate the efficacy of topical tacalcitol and sunlight exposure in the treatment of adult nonsegmental vitiligo.

BACKGROUND: Vitiligo is a common skin disease which is difficult to treat. Approximately half of patients acquire the disease before the age of 20 years. This disease has a high stigmatizing impact but no ideal, aetiology-oriented, effective therapy has been found to date. Tacalcitol and other vitamin D analogues have been shown to have stimulating activity both on immunomodulatory mediators and on melanocytes in lesional skin. OBJECTIVE: To investigate the efficacy and safety of tacalcitol ointment plus sunlight exposure in the treatment of nonsegmental vitiligo. METHODS: A single-centre, randomized, double-blind, vehicle-controlled study including 80 patients with nonsegmental vitiligo was carried out in a specialized outpatient dermatology clinic within a tertiary care, university-affiliated hospital in Spain. Efficacy was assessed by quantification of the lesional repigmentation area at the end of the study compared with the baseline. Tacalcitol (n = 40) or matching placebo ointment (n = 40) was applied once a day at night. Daily exposure to sunlight for 30 min was performed. Treatment was continued for 4 months. The response of the lesions was clinically verified every 2 weeks by a blinded medical investigator. All adverse effects were recorded. RESULTS: Eighty adult patients with nonsegmental vitiligo were recruited. Over 16 weeks, 64 patients completed the study requirements. There was no significant difference in the repigmentation response at the 16-week time point between the vehicle + sunlight exposure and the tacalcitol + sunlight exposure groups. No reduction in the size of the lesions > 25% was observed in the tacalcitol-treated patients. No serious adverse effects were observed. CONCLUSION: The combination of tacalcitol with heliotherapy has no additional advantages compared with heliotherapy alone.

Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study.

BACKGROUND: Becocalcidiol is a vitamin D(3) analogue which has not caused hypercalcaemia or significant irritation in preclinical trials. OBJECTIVES: To evaluate the efficacy and safety of two dosing regimens of becocalcidiol ointment (low dose = 75 microg g(-1) once daily for 8 weeks; high dose = 75 microg g(-1) twice daily for 8 weeks) in the treatment of plaque-type psoriasis. METHODS: One hundred and eighty-five subjects with chronic plaque-type psoriasis affecting 2-10% of their body surface area took part in a multicentre, double-blind, parallel-group, vehicle-controlled, randomized controlled trial comparing topical application of placebo, becocalcidiol 75 microg g(-1) once daily (low dose) or becocalcidiol twice daily (high dose) for 8 weeks. Main outcomes included Physician's Static Global Assessment of Overall Lesion Severity (PGA) score; Psoriasis Symptom Severity (PSS) score; adverse events; and laboratory assessment. RESULTS: In the intent-to-treat population at week 8, high-dose becocalcidiol was statistically superior to vehicle [P = 0.002; 95% confidence interval (CI) 6.7-32.2], with 16 of 61 (26%) subjects achieving a PGA score of clear or almost clear. Greater improvement in PSS score was seen with high-dose becocalcidiol than with vehicle, but this result did not quite achieve statistical significance (P = 0.052; 95% CI -16.2 to 0.1). In all groups, therapy was safe and well tolerated, with fewer subjects experiencing irritation than is reported in studies using calcipotriol. CONCLUSIONS: Treatment with high-dose topical becocalcidiol for 8 weeks led to almost or complete clearing of moderate plaque-type psoriasis in over a quarter of patients. Therapy was safe and well tolerated.

Profile of clinical efficacy and safety of topical tacalcitol.

Several topical treatments such as ointments, keratolytics, dithranol, tar, corticosteroids and Vitamin D3 analogues are commonly used in the treatment of mild and/or moderate psoriasis. These treatments can be associated with a variety of local and systemic side effects, as well as to very often unsatisfactory results. The purpose of this critical review of the literature is to evaluate the efficacy and tolerability of the synthesis of new analogues of the Vitamin D3 Tacalcitol, which is formulated in ointment form at a concentration of 4 microg/g, for the treatment of mild and/or moderate psoriasis (involvement of <20% of the surface of the skin) and to evaluate whether this drug can be used in the treatment of other skin conditions. Based on existing data in the literature, Tacalcitol is an effective drug for the topical treatment of psoriasis and is also able to ensure that the effects last over time, even after treatment has stopped. Tacalcitol is also well tolerated because the onset of side effects, such as local irritation, pruriginous or burning sensations, were reported in only a small percentage of the subjects who were treated. Lastly, the marked regulatory effects it has on the proliferation and differentiation of keratinocytes, as well as on the immunocompetent cells, has led to suggestions that Tacalcitol may be used in other keratinisation disorders and in some hyperproliferative skin diseases. Evaluation of the effective indications to use in these conditions still requires further data confirming its effectiveness, opening the way to wider use of this molecule in dermatology.

Tacalcitol in the treatment of psoriasis vulgaris: the Spanish experience.

BACKGROUND: A group of vitamin D derivatives has revealed to be an efficient treatment for psoriasis. Different types of studies have been designed to confirm the efficacy of its use without relevant side-effects. OBJECTIVE: Evaluation of tolerability and efficacy of tacalcitol ointment in moderate psoriasis. DESIGN: A 2-month multicentre prospective open-label observational study in patients with psoriasis treated with tacalcitol ointment. METHODS: A cohort of patients with psoriasis vulgaris seeking medical advice and being treated with tacalcitol based on the decision of their dermatologists was selected. A 2-month follow-up was performed to assess efficacy and tolerability of tacalcitol in an ointment formulation (4 microg/g) once daily. A psoriatic lesion was selected in each patient in order to assess clinical symptoms (erythema, desquamation and thickness) by means of five-point scale: 0 (none) to 4 (maximal severity). Percentages of involved skin, adverse effects, physicians' global assessments of efficacy and tolerability, and patients' global satisfaction scores were also evaluated after 15-30 days (first visit) and 2 months (second visit) of treatment. RESULTS: A total of 556 patients were included. Mean psoriasis duration was 10.1 years (range, 0-61 years). Follow-up data were available for 493 patients in first follow-up visit and 449 in second (final) visit. Adverse events were uncommon (1.0% and 0.6% of patients in first and second follow-up visits, respectively). At first follow-up visit, mean decrease in selected lesions surface area (from a baseline value of 185.8 cm(2) per lesion) was 11.1 cm(2) (95% CI, 1.6-20.6; P = 0.0213). After 2 months of treatment, mean scores for erythema, desquamation and thickness changed from 2.2 +/- 0.8 to 1.1 +/- 0.8 (19% of patients with no erythema at final visit); from 2.4 +/- 0.8 to 0.6 +/- 0.7 (55% of patients with no desquamation); and from 2.2 +/- 0.9 to 0.8 +/- 0.6 (51% of patients with less thickness), respectively. Mean percentage of total body skin involvement was 14% (7.5% and 6.9% of anterior and posterior body surface, respectively). After 2 months of treatment, a 3.2% (95% CI, 2.7-3.8; P = 0.0001) and 3.0% (95% CI, 2.4-3.6; P = 0.0001) decrease was observed in the percentage of involved anterior and posterior skin surface area, respectively. Efficacy and tolerability evaluation by investigators was very good or good in 94% and 74% of patients, respectively; 78% of patients evaluated study treatment as satisfactory/very satisfactory. More than 80%, 50-80% and less than 50% of prescribed doses were used by 88%, 9.3% and 2.3% of patients, respectively. CONCLUSIONS: Tacalcitol was highly effective in the symptomatic treatment of moderate psoriasis. Compliance was very high, probably due to the easy and convenient application. Physicians' global assessments of tacalcitol were excellent, both for tolerability and efficacy. Excellent tolerability was confirmed by the low rate of adverse events. Our results in an everyday clinical setting show that tacalcitol is a useful therapy in patients with moderate psoriasis.

[Treatment of scalp psoriasis. An effective and safe tacalcitol emulsion]. / Behandlung der Kopfhaut-Psoriasis. Gute Wirksamkeit und Sicherheit durch Tacalcitol-Emulsion.

BACKGROUND: The scalp is a problematic area in psoriasis where treatment is often difficult. The lesions often extend beyond the hairline to involve the forehead, neck and sensitive facial skin. Topical corticosteroids and potentially irritant topical preparations have only limited utility in these sensitive areas. Most of the patients additionally suffer from psychosocial problems due to the visibility of lesions. OBJECTIVE: The aim of this multicenter, prospective, randomized, double-blind study, was to assess efficacy, safety and tolerability of once daily tacalcitol emulsion (4 micro g/g) compared to placebo in the treatment of scalp psoriasis. METHODS: To determine efficacy, safety and tolerability, 273 patients with mild to moderate scalp psoriasis were treated over a 8-week period. Response to treatment was evaluated using the sum score of erythema, infiltration and scaling. Global improvement of psoriasis was rated by the investigators and the patients using a 5-point scale. In addition the single scores of erythema, infiltration and scaling were assessed by the investigators, and the patients were asked to evaluate the intensity of itching and scaling over the treatment period. RESULTS: Tacalcitol was significantly superior to placebo in reducing the severity of scalp psoriasis. At the end of the study, the median sum score decreased by 53% in the tacalcitol group and was significantly better than placebo with 30% (p<0.0001). Global assessment of improvement was significantly greater in the tacalcitol group in both investigator and patient evaluation. 80% of patients on tacalcitol showed improvement to clearance and was statistically significant better than placebo (p <0.0001) in the investigator rating after 8 weeks. Tacalcitol was significantly superior to placebo in reducing erythema, scaling and infiltration, and in the patient assessment in reducing scalp scaling and itching. Treatment was very well tolerated. Local reactions were transient and uncommon. Their incidence was similar in both treatment groups. No serious side effects were reported, including those relating to calcium homeostasis or vitamin D(3) metabolism. No changes in mean levels of serum calcium, parathyroid hormone (PTH), calcitriol and in 24h-urinary excretion were observed. CONCLUSION: The results of this study indicate that topical application of tacalcitol (4 micro g/g) emulsion once daily is an effective, safe and very well- tolerated treatment for scalp psoriasis.

Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with thiazide diuretics in a case of psoriasis.

Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of inflammatory skin diseases such as psoriasis. Hypercalcemia has not been previously reported during treatment with topical tacalcitol. We experienced a male patient with psoriasis and hypertension whose conditions were treated with tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and urinary excretion of calcium increased gradually. On day 28 of the treatment, his serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was terminated, seven days later, the serum calcium level had returned to the reference range without any specific treatment. The present case is the first report of hypercalcemia induced by vitamin D3 ointment and thiazide simultaneously.

A systematic review of adverse effects associated with topical treatments for psoriasis.

Mild to moderate psoriasis is a disease that can often be treated with topical medications. The diversity of topical therapies and their disparate side effects complicates treatment planning. Our purpose is to compare the rates of adverse events associated with different topical psoriasis treatments. A review of medical literature from 1996 to March, 2002 was conducted using guidelines set by QUORUM statement criteria. In monotherapy studies, corticosteriods caused fewer adverse reactions compared to vitamin D analogues and tazarotene. In combination studies adverse event rates were higher than in monotherapy studies, except for the combination of topical steroid and calcipotriene which decreased irritation. Irritant contact dermatitis was the main side effect with vitamin D analogues, tazarotene, dithranol or coal tar, while side effects of topical corticosteriods included headache, viral infection and skin atrophy. Topical agents for psoriasis are usually well-tolerated without severe side effects. Formulating a patient's medication regimen should take into account the needs for short-term management and long-term control of psoriasis. Since clearance is not a realistic expectation, reasonable goals should be set as excessive use of topical treatments may increase the risk of both cutaneous and systemic side effects.

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

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

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

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

The safety of calcitriol 3 microg/g ointment. Evaluation of cutaneous contact sensitization, cumulative irritancy, photoallergic contact sensitization and phototoxicity.

Vitamin D analogues are widely used for the treatment of psoriasis. A new topical formulation of calcitriol (3 microg/g ointment) has been shown to be effective in the treatment of stable plaque-type psoriasis. This paper reports the results of four separate studies designed to evaluate specific local-safety parameters: cumulative irritancy, cutaneous contact sensitization, potential photoallergic contact sensitization and phototoxicity. Calcitriol 3 microg/g ointment was classified as non-irritant when compared to calcipotriol, tacalcitol and white petrolatum. Petrolatum and tacalcitol were slightly irritant and calcipotriol moderately irritant. No sensitization was observed with calcitriol 3 microg/g ointment. With regard to phototoxic potential, sites treated with calcitriol 3 microg/g ointment or vehicle ointment were less irritated than those treated with white petrolatum or those that were untreated. Using standard photoallergenicity testing methodology, there were no skin reactions of a photoallergic nature to the study material. These studies showed that calcitriol 3 microg/g ointment is a well-tolerated treatment for stable plaque-type psoriasis.

Comparison of the relative effects of 1,24-dihydroxyvitamin D(2) [1, 24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1,24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on selected vitamin D-regulated events in the rat.

The present experiments were conducted to compare the relative hypercalciuric and hypercalcemic activities of 1,24-dihydroxyvitamin D(2) [1,24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1, 24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] in 7-week-old rats. The rats were dosed orally with each sterol for 7 days at a rate of 1 ng/g body weight/day. We also monitored the effect of the three compounds on the induction of mRNA for CaATPase and for 25-hydroxyvitamin D-24-hydroxylase in the kidney and intestine, on plasma vitamin D metabolite levels, and on the capacity to evoke modification in the vitamin D receptor/retinoic acid X receptor (VDR/RXR) heterodimer conformation. Plasma calcium was elevated in the rats treated with 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3), but not in the 1,24-(OH)(2)D(2)-dosed rats. Urinary calcium was elevated significantly (relative to controls) in all groups. The order of hypercalciuric activity was 1,25-(OH)(2)D(3) >/= 1,24-(OH)(2)D(3) >/= 1,24-(OH)(2)D(2) > control. Duodenal plasma membrane calcium ATPase (PMCA) mRNA was elevated to a similar extent in all groups relative to controls. Duodenal 24-hydroxylase mRNA was elevated in all groups relative to controls; however, the elevations were significantly higher in the 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3) groups compared with the 1,24-(OH)(2)D(2) group. Kidney 24-hydroxylase also was elevated significantly in the 1, 24-(OH)(2)D(3)- and 1,25-(OH)(2)D(3)-treated rats but not in the 1, 24-(OH)(2)D(2)-treated rats. Recombinant human vitamin D receptor (hVDR) extracts were incubated with saturating concentrations of 1, 24-(OH)(2)D(2), 1,24-(OH)(2)D(3), and 1,25-(OH)(2)D(3) and subsequently analyzed by electrophoretic mobility shift assay (EMSA). Overall binding was comparable for all metabolites; however, the 1, 24-(OH)(2)D(2) complex exhibited distinctly altered mobility relative to 1,24-(OH)(2)D(3) and 1,25-(OH)(2)D(3), suggestive of an effect on hVDR/hRXR conformation. These data suggest that 1, 24-(OH)(2)D(2) is not as potent as either of the vitamin D(3) sterols at affecting hypercalcemia or hypercalciuria in young growing rats; however, 1,24-(OH)(2)D(2) can evoke other biological responses similar to the vitamin D(3) sterols. These different responses may be related to the alterations in conformation state of the hVDR/hRXR heterodimer.

Placebo-controlled evaluation of the irritant potential of tacalcitol (1a,24-dihydroxyvitamin D3) in healthy volunteers.

In the treatment of psoriasis with topical vitamin D3 analogues, lesional and perilesional irritation is the main side-effect. The aim of this study was to investigate whether local side-effects generated by tacalcitol, a vitamin D3 analogue, show concentration dependence. 3 different concentrations of tacalcitol (0.4; 4; 40 microg/g ointment) and the vehicle were applied on normal skin of the back of 25 healthy volunteers under occlusive conditions for 5 days. Assessment of erythema, infiltration and scaling as well as measurement of transepidermal water loss (TEWL) was performed on days 1 to 5. On day 5, additional skin barrier tests (DMSO test, alkali resistance test) were performed. Erythema and slight infiltration, but no scaling, were observed in a number of subjects without significant differences. TEWL also did not show significant differences for the test formulations, though there was a tendency towards lower values in the untreated areas. In the skin barrier tests, a tendency towards higher alkali resistance in the test areas treated with 40 microg tacalcitol/g ointment was detected. Thus, under occlusive conditions, the irritant potential of tacalcitol is very low. There is no convincing evidence of concentration dependence in irritation generated by tacalcitol when applied under occlusive conditions.

An update on vitamin D3 analogues in the treatment of psoriasis.

Vitamin D3 analogues have revolutionized the topical treatment of psoriasis during the last decade. The mode of action of this ligand for the vitamin D3 receptor is via modulation of the transcription of genes with vitamin D3 response elements in their promoter region. Vitamin D3 analogues cause inhibition of various aspects of cutaneous inflammation and epidermal proliferation with enhancement of normal keratinization. In vivo, active vitamin D3 analogues proved to have a substantial antipsoriatic effect. Calcipotriol (50 micrograms/g in ointment or cream), tacalcitol (4 micrograms/g in ointment) and calcitriol (3 micrograms/g in ointment) have been shown to have an antipsoriatic effect in placebo-controlled studies. The most extensive body of information on comparative studies and on combination therapies is available for the analogue calcipotriol. So far, calcipotriol is available as a routine treatment in most countries, whereas tacalcitol has been registered in Japan and some European countries. From the available data in the literature we may conclude that calcipotriol is a first-line treatment for psoriasis and is advantageous in the combination with several other antipsoriatic treatments such as topical corticosteroids, PUVA, cyclosporin and acitretin. Tacalcitol 4 micrograms/g as a once-daily principle is effective in psoriasis. Comparative studies will indicate the position of the existing and new vitamin D3 analogues.

Current experience with tacalcitol ointment in the treatment of psoriasis.

Various controlled studies have demonstrated the efficacy and safety of tacalcitol ointment (4 micrograms/g) in the treatment of psoriasis. Further data are now available from a multicentre post-marketing surveillance study involving more than 5000 outpatients. Once-daily treatment with tacalcitol resulted in a marked decrease of mean sum score (erythema, infiltration, scaling) from 6.3 to 2.7 score points in an average period of 61 days. Efficacy was assessed by dermatologists as 'very good' or 'good' in 71% of the patients. Local tolerance was stated to be 'very good' or 'good' in 94% of the patients. Only 1% of the patients experienced skin irritation. No case of hypercalcaemia was observed. Compared with conventional therapies, 52% of the patients saved up to half an hour of treatment time daily because of the once-daily application. Good local tolerance and a convenient treatment regimen may also help compliance.