Efficacy of topical treatment in psoriasis with MC903, a new vitamin D analogue. A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis. Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis. Topical paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot study. Comparing clobetasol propionate 0.05% spray to calcipotriene 0.005% betamethasone dipropionate 0.064% ointment for the treatment of moderate to severe plaque psoriasis. Evaluation of halobetasol propionate ointment in the treatment of plaque psoriasis: report on two double-blind, vehicle-controlled studies. Intra-individual comparison of the cutaneous safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or flexural areas. Rationale for use and clinical responsiveness of hexafluoro-1,25-dihydroxyvitamin D3 for the treatment of plaque psoriasis: a pilot study.
In 10 in-patients with chronic plaque psoriasis, the antipsoriatic effect of MC903, a new synthetic analogue of vitamin D was evaluated. In each patient two symmetrical located psoriatic plaques were selected for the study. Topical treatment with MC903 cream (containing 1.2 mg MC903 per g cream) was compared with placebo cream in a double-blind, controlled, left-right, randomized way during 6 weeks of therapy. Compared with baseline, the clinical (erythema, scaling and infiltration) improvement was significant after 1 week of therapy with MC903 cream, while lateral comparison showed MC903 cream significantly better than cream base after 4 weeks of therapy (p less than 0.05). Measurements of skin blood flow by the laser Doppler technique in evaluating the disease activity was not superior to the clinical assessments. In 3 patients the psoriatic lesions treated with MC903 cream cleared completely during 6 weeks of therapy. No essential adverse reactions were observed. MC903 has a potent effect on cell proliferation and cell differentiation, but has minimal effect on calcium metabolism. It is concluded that this synthetic vitamin D analogue is potentially useful in the treatment of psoriasis. The efficacy and safety of halobetasol propionate 0.05% cream, an ultra high-potency corticosteroid preparation, was evaluated in a double-blind, vehicle-controlled, paired comparison study. Patients' psoriatic lesions were evaluated before treatment and after 1 and 2 weeks of twice-daily treatment with halobetasol propionate and vehicle. Response measures (plaque elevation, erythema, scaling, and pruritus) were evaluated with a 4-point severity scale whereby the sum provided a total score. Patient self-assessment measures were obtained at the 2-week visit by categorizing his or her global responses to queries about each treatment's "effectiveness" and "overall rating." All efficacy parameters, as judged by the physician, showed statistically significant (p = 0.0001) treatment differences favoring halobetasol propionate at both week 1 and week 2 evaluations. Patient global responses for "effectiveness" and "overall rating" favored halobetasol propionate 0.05% cream over vehicle after 2 weeks of use. No systemic adverse drug effects were reported during the study. No patient was discontinued from the study because of an adverse event, and there was no evidence of skin atrophy after 2 weeks of treatment with either agent. Patient reports of "stings" or "burns" were equally distributed between the active and vehicle treatment groups. This trial demonstrates that halobetasol propionate 0.05% cream is clinically beneficial and without evidence of significant risk in the treatment of plaque psoriasis. Ninety psoriasis patients, who were either completely cleared of or manifested only a minimal presence of disease signs following 3-4 weeks of twice daily treatment with augmented betamethasone dipropionate (ABD) ointment 0.05%, were enrolled in this multicenter, double-blind, placebo-controlled study. The study was designed to determine if an intermittent pulse dose regimen of ABD ointment could safely and effectively maintain a remission disease status when treatment was applied in three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months. The disease of 60% of the patients in the active treatment group was successfully controlled for 6 months, while 80% of the placebo-treated patients experienced exacerbation of disease signs. No serious local or systemic treatment-related adverse experiences were reported. ABD ointment 0.05%, when applied using the intermittent treatment regimen described here, was shown to be a clinically beneficial and well-tolerated method of long-term (up to 6 months) maintenance therapy for psoriasis patients. 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. There continues to be a need to develop new pharmacological approaches for treating psoriasis. Topical active vitamin D compounds have proven to be both safe and effective for treating psoriasis. Paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D(2)) is a novel vitamin D analogue which has been developed for the prevention of secondary hyperparathyroidism in patients with chronic renal failure.
                To investigate the efficacy and safety of 12 weeks' therapy with a once-daily application of paricalcitol ointment (15 microg g(-1)) in comparison with placebo ointment.
                This pilot double-blinded self-controlled study was initiated in 11 patients with moderate plaque psoriasis. To characterize the biological effects further and to evaluate the efficacy of topical paricalcitol treatment in psoriasis, we have analysed immunohistochemically the expression of one of the markers for epidermal differentiation (transglutaminase K) in paricalcitol-treated skin as compared with placebo treatment.
                Treatment with paricalcitol was superior to placebo treatment beginning at week 1. The global severity score for erythema, plaque elevation and scaling was improved significantly more by paricalcitol ointment than by placebo (P < 0.001). Similar results were obtained for assessments of scaling, erythema and plaque elevation. No symptoms of local skin irritation were noted. Laboratory parameters including serum calcium, phosphorus, parathyroid hormone and urinary calcium/creatinine ratio did not reveal any changes of clinical relevance during treatment. The immunoreactivity of transglutaminase K changed after 12 weeks of paricalcitol treatment almost completely to the pattern characteristic for nonlesional psoriatic skin.
                Once-daily application of paricalcitol ointment was safe and effective for the treatment of plaque psoriasis. Topical corticosteroids are widely used in the treatment of psoriasis. This study was conducted to compare the efficacy and safety of clobetasol propionate (CP) 0.005% spray to calcipotriene 0.005%-betamethasome diproprionate 0.064% (C-BD) ointment in patients with moderate to severe plaque psoriasis. Assessments were made at baseline, week 2, week 4 (end of treatment) and week 8 (4 weeks posttreatment). An assessment for Overall Disease Severity (ODS) found that 75% of CP spray-treated patients achieved a rating of clear or almost clear after 4 weeks of treatment compared to 45% of C-BD ointment-treated patients (P=.003). Adverse events were reported by less than one-third of patients from each treatment group (31% for CP spray and 33% for C-BD ointment). The results of two studies are presented that reveal the efficacy and safety of 0.05% halobetasol ointment in the treatment of patients with plaque psoriasis of at least moderate severity. Both multicenter studies were randomized, double-blind, and vehicle controlled, and study medications were applied twice daily for 2 weeks. One study was a paired-comparison (PC); the other study was of parallel-group (PG) design. Both studies called for evaluations at entry (week 0) and after 1 and 2 weeks of treatment. The PC study enrolled 100 patients; the PG study enrolled 110 patients; 204 patients provided efficacy data over both studies. In the PC study, plaque elevation, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistical (p less than or equal to 0.0003) and clinical significance (all greater than 1-unit difference on the rating scale) favoring 0.05% halobetasol ointment over vehicle. Pruritus (initially mild) and total score also showed statistically significant treatment differences favoring halobetasol at the final evaluation. Patient global responses for "effectiveness" and "overall rating" favored 0.05% halobetasol ointment over vehicle. In the PG study, induration, erythema, and scaling, at least moderately severe at entry, showed at the end of treatment both statistically and clinically significant differences favoring 0.05% halobetasol ointment over vehicle. Physician's global evaluation favored 0.05% halobetasol ointment over vehicle after 2 weeks of use. No patients were released from either study because of adverse events. No systemic adverse events or findings of skin atrophy were reported in these studies. Reports of "stings" or "burns" were equally divided between halobetasol and its vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) Psoriasis involving sensitive skin areas remains difficult to treat because of the side-effects of topical corticosteroids and the irritancy potential of vitamin D3 derivatives. Several clinical trials have demonstrated that calcitriol, the naturally occurring and hormonally active form of vitamin D3, is effective and safe at the dose of 3 microg g(-1) for the treatment of psoriasis affecting the trunk and limbs.
                We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas. One pair of symmetrical and bilateral target lesions was selected from each area and assessed for perilesional erythema, oedema, and stinging/burning. Global assessment of local tolerability and global improvement were rated by the investigator, and the subjects were asked to evaluate the tolerability and efficacy of each product and to express their global preference.
                In the 75 subjects, calcitriol and calcipotriol both led to clearing of at least one target lesion in 21 (28%) of the subjects each. Perilesional erythema (P < 0.001), perilesional oedema (P < 0.02) and stinging/burning (P < 0.001) were all significantly less severe with calcitriol than with calcipotriol. The subjects' evaluation of local tolerability was significantly (P < 0.0001) in favour of calcitriol. Ten treatment-related dermatological events occurred in eight subjects, including one subject who experienced skin discomfort on both sides. All other events occurred only on the calcipotriol-treated side (irritant dermatitis, six subjects; contact dermatitis, one subject). Global assessment of improvement from baseline by the investigators was significantly greater for the calcitriol-treated lesions (P < 0.02). The subjects' global preference was significantly in favour of calcitriol (P < 0.02).
                In the present study, calcitriol ointment was found to be better tolerated and would appear to be more effective than calcipotriol ointment in the treatment of psoriasis in sensitive areas. Vitamin D analogues are useful in topical therapy of psoriasis.
                To evaluate the effect of hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) in treatment of psoriasis.
                Fifteen patients with plaque-type psoriasis were enrolled in a single centre double-blind, right/left comparison, placebo-controlled study, and received 0.1 g of petrolatum containing 5 microg of F6-1,25(OH)2D3 or 0.1 g of petrolatum (placebo) for 3 months. After completion of this double-blind study, a subset of these patients (n = 12) applied F6-1,25(OH)2D3 ointment (50 microg g-1 of petrolatum) to all their lesions (total area, 100-5000 cm2, mean area: 3300 m2) for 2 months as a single application at night.
                The mean severity score in the right/left-sided controlled topical F6-1,25(OH)2D3 (50 microg g-1) therapy group showed a decrease of 85%. In contrast, the mean severity score for the placebo-treated areas showed a decrease of 45% (P < 0.001). In the 12 patients who subsequently applied F6-1,25(OH)2D3 (50 microg g-1) ointment to all of their lesions, 91.6% showed moderate to excellent improvement. The mean Psoriasis Area and Severity Index score decreased by 44.9% (from 33.6 +/- 15 to 18.5 +/- 13). No effect on calcium homeostasis was noted. Adverse events included mild irritation in two patients that resolved during therapy.
                Topical F6-1,25(OH)2D3 is a safe and effective once a day treatment for psoriasis.
Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data.