John Sefton

Tazarotene gel, a new retinoid, for topical therapy of psoriasis: Vehicle-controlled study of safety, efficacy, and duration of therapeutic effect

BACKGROUND Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis. OBJECTIVE Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods. METHODS In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment. RESULTS Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation. CONCLUSION Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Response of psoriasis to a new topical retinoid, AGN 190168

BACKGROUND Oral retinoids have been widely used in psoriasis, but topical forms have been ineffective or irritating. OBJECTIVE Our purpose was to determine the clinical and molecular effects of a new topical retinoid, AGN 190168, on psoriasis. METHODS Seven patients with psoriasis were treated for 2 weeks with topical retinoid and 2 weeks with vehicle. Two control subjects with psoriasis were treated for 2 weeks with vehicle alone. Biopsy specimens from normal skin as well as from untreated and treated psoriatic lesions were compared by immunohistochemical analysis. Differentiation and inflammatory markers were studied. RESULTS Clinical improvement was seen in all seven patients after 2 weeks of treatment. Improvement was still present, but not significant, after 2 additional weeks of vehicle application. Histologic examination showed a return to a more normal morphology in four of seven biopsy specimens, which correlated with filaggrin expression. There was a diminution in the precocious expression of keratinocyte transglutaminase, keratin 16, and involucrin, as well as a decrease in epidermal growth factor receptor and in the number of cells expressing intercellular adhesion molecule type 1 and HLA-DR. CONCLUSION Clinical and histologic improvements were seen in psoriasis in association with the topical application of AGN 190168 at 2 weeks, including decreased inflammation and restoration of normal epidermal differentiation. Small patient numbers and the possibility that the changes were related to clinical improvement alone and not the topical agent preclude definitive conclusions.

Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis.

Abstract Background: Topical corticosteroids are often used in the treatment of psoriasis, but long-term use may be associated with serious adverse events such as tachyphylaxis or atrophy of the skin. Tazarotene, a new topical retinoid, has demonstrated significant clinical benefits but can cause mild to moderate local irritation. Objective: We evaluate whether a combination treatment of topical tazarotene and a topical corticosteroid would increase efficacy while reducing the incidence of local adverse events associated with a topical retinoid. Methods: Three hundred patients enrolled in an investigator-masked study were randomly assigned to 1 of 4 treatment groups: tazarotene 0.1% gel in combination with placebo cream, or with a low-, mid-, or high-potency corticosteroid cream, for 12 weeks of treatment and a posttreatment follow-up at week 16. Results: Tazarotene 0.1% gel in combination with a mid- or high-potency corticosteroid, when compared with tazarotene plus placebo cream, achieved significantly greater reductions in scaling, erythema, and overall lesional severity, and a decreased incidence of adverse events. Conclusion: All tazarotene combinations (including tazarotene plus placebo) were highly effective in rapidly reducing the severity of psoriasis. Combining tazarotene with a topical corticosteroid increased efficacy while reducing the incidence of local adverse events. (J Am Acad Dermatol 1998;39:590-6.)

Once-daily tazarotene gel versus twice-daily fluocinonide cream in the treatment of plaque psoriasis

BACKGROUND A new class of topical receptor-selective acetylenic retinoids, the first of which is tazarotene, has been developed. OBJECTIVE Our purpose was to compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide 0.05% cream in the treatment of patients with plaque psoriasis. METHODS Three hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients completed a multicenter, investigator-masked, randomized, parallel-group clinical trial. RESULTS Both tazarotene gels were as effective as fluocinonide in reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of trunk/limb lesions at all study weeks except week 4. Tazarotene 0. 1% gel was similar to fluocinonide in reducing scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly greater effect on erythema than tazarotene at weeks 2 through 8. However, treatments were not significantly different at week 12, and tazarotene demonstrated significantly better maintenance of therapeutic effect after cessation of therapy. CONCLUSION Tazarotene 0.1% and 0.05% gels were safe and effective in the treatment of mild-to-moderate plaque psoriasis.

Efficacy of a sunscreen containing butyl methoxydibenzoylmethane against ultraviolet. A radiation in photosensitized subjects

Topical formulations containing a new chemical entity, the ultraviolet A absorber Parsol 1789 (butyl methoxydibenzoylmethane), were evaluated as agents for protecting human skin against ultraviolet A (UVA) radiation. Healthy subjects were photosensitized to UVA radiation by ingestion of 8-methoxypsoralen (0.6 mg/kg). After 90 minutes, five formulations (vehicle, vehicle + butyl methoxydibenzoylmethane, vehicle + butyl methoxydibenzoylmethane + padimate O, vehicle + padimate O, and a marketed sunscreen containing padimate O, oxybenzone, and octyl salicylate) were applied in a randomized, double-blind manner to areas on the lower part of the back. Thirty minutes later, sites in the five treated areas and in a sixth unprotected area were exposed to graduated doses of UVA radiation. Test sites were evaluated for erythema 48 and 72 hours after UVA exposure, and for melanogenesis approximately 2 weeks later. The combination of butyl methoxydibenzoylmethane + padimate O demonstrated significantly greater protection than the combination of padimate O, oxybenzone, and octyl salicylate.

Indoor and outdoor efficacy testing of a broad-spectrum sunscreen against ultraviolet A radiation in psoralen-sensitized subjects

The efficacy of a sunscreen containing an investigational drug, butyl methoxydibenzoylmethane in combination with padimate O against the erythemogenic effect of ultraviolet A (UVA) radiation was evaluated in two double-blind studies involving subjects sensitized with topical 8-methoxypsoralen. UVA radiation was supplied from either a filtered solar simulator (indoors) or filtered sunlight (outdoors). Five formulations were tested: 3% butyl methoxydibenzoylmethane and 7% padimate O, 7% padimate O, 5% octyl salicylate, and 3% oxybenzone, 3% butyl methoxydibenzoylmethane alone, 7% padimate O alone, and vehicle. Sunscreen protection against the erythemogenic effect of UVA radiation was expressed as phototoxic protection factors. The phototoxic protection factor for each sunscreen was derived from a ratio of the minimal phototoxic dose of UVA radiation that produced delayed erythema on sunscreen-protected and unprotected skin. The combination of 3% butyl methoxydibenzoylmethane and 7% padimate O provided significantly greater protection than the other sunscreen formulations, and for each sunscreen the phototoxic protection factors determined indoors and outdoors were comparable.

Erythromycin 2% gel in comparison with clindamycin phosphate 1 % solution in acne vulgaris

One hundred two patients with mild to moderate facial acne vulgaris completed a 12-week, investigator-masked, randomized, parallel-group comparison of a gel formation of erythromycin (2%) with clindamycin phosphate 1% solution. Patients were evaluated at a baseline visit and after 4, 8, and 12 weeks of twice-daily treatment. Both medications significantly reduced the numbers of papules and open and closed comedones. No significant differences in lesion count reductions were detected between the treatment groups after 8 and 12 weeks of treatment. By the end of 12 weeks, 48% of the patients in the erythromycin group and 47% in the clindamycin group had good or excellent responses to treatment. No patient was terminated from the study for side effects. Most patients, 65% in the erythromycin 2% gel group and 67% in the clindamycin phosphate 1% solution group, had a favorable impression of the overall cosmetic characteristics of their study medication.

Naftifine cream 1% versus econazole cream 1% in the treatment of tinea cruris and tinea corporis

Data from 104 subjects with tinea cruris or tinea corporis were evaluated in this double-blind, randomized study. The subjects applied naftifine cream 1% or econazole nitrate cream 1% to affected areas twice daily for 4 weeks. After 1 week of treatment naftifine had an overall cure rate of 19% compared with 4% for econazole (p = 0.03). A difference in favor of naftifine, although not statistically significant after the first week, persisted throughout treatment. Two weeks after the end of treatment both medications had overall cure rates of approximately 80%. Three percent of the naftifine-treated subjects had side effects compared with 13% of the econazole-treated subjects. In two subjects using econazole, the side effects were severe enough to warrant discontinuation of treatment.

Addition of a topically applied corticosteroid to a modified Goeckerman regimen for treatment of psoriasis: Effect on duration of remission

A double-blind parallel group study was undertaken to assess the effect of adding a topically applied corticosteroid cream to a modified Goeckerman regimen to treat patients with psoriasis. Nineteen patients with psoriasis were treated with either this regimen and hydrocortisone valerate cream or the regimen and vehicle cream. Patients were given daily treatments until their skin cleared or until twenty-eight treatments were received. They were then followed up until rebound or relapse occurred or 6 months had passed. The addition of hydrocortisone valerate cream to the modified Goeckerman regimen led to relapse after 5.9 weeks in comparison with 17.9 weeks for the control group.

Double-blind comparison of naftifine cream and clotrimazole/betamethasone dipropionate cream in the treatment of tinea pedis

chenoid infiltrate of lymphocytes. Immunofluorescence examination of a perivesicular papule was characterized by numerous ovoid bodies scattered in the papillary dermis. These stained for IgM, IgG, and fibrinogen. IgG, C3, and fibrinogen were also deposited linearly along the dermoepidermal junction. Immunofluorescence studies on normal-appearing skin showed a strong linear band of IgG and C3 at the dermoepidermal junction without staining of colloid bodies. Serum and blister fluid were positive at a titer of 1:80 for basement membrane zone (BMZ) antibodies. A diagnosis ofLPP was made. She was initially treated with prednisone, 40 mg daily (1.5 mg/kg/day), with a good response, no new vesicles appeared and the papular lesions cleared. After 2 weeks circulating BMZ antibodies decreased to a titer of 1:20. The dosage of prednisone was reduced to 20 mg daily for 14 days and then discontinued. Topical fluorinated corticoids were administered for an additional month. At that time she had resolution of all lesions. Two months later, she had a relapse of LP, without blistering, on both ankles. At the time of relapse circulating BMZ antibodies were absent.