Deborah A. Lew-Kaya

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.)

Pharmacokinetics of Tazarotene Cream 0.1% After a Single Dose and After Repeat Topical Applications at Clinical or Exaggerated Application Rates in Patients with Acne Vulgaris or Photodamaged Skin

AbstractObjective: To evaluate the safety and pharmacokinetics of tazarotene cream 0.1% under standard (face only) or exaggerated (15% body surface area, including the face) application conditions after a single dose and after repeat topical applications once daily to patients with acne vulgaris or photodamaged skin. Methods: Two separate, randomised, single-centre, nonblinded, parallel-group pharmacokinetic studies were conducted. In one study, tazarotene cream 0.1% was applied either to the face of eight female patients with moderate acne or to 15% body surface area of ten female patients with severe acne. In the other study, tazarotene cream 0.1% was applied either to the face (six females, two males) or to 15% body surface area (8 females, 8 males) of patients with photodamaged skin. In both studies, tazarotene cream 0.1% was applied once daily (except on days 1 and 2) for 30 days. Blood was drawn for measurement of plasma concentrations of tazarotenic acid at defined time intervals after application of the cream. Plasma tazarotenic acid concentrations were determined by a validated gas chromatography-tandem mass spectrometry method with a lower limit of quantification of 0.005 μg/L. Results: At exaggerated application rates in patients with acne vulgaris, the maximum average peak concentration (Cmax) and 24-hour area under the concentration-time curve (AUC) values of tazarotenic acid were (mean ± SD) 1.20 ± 0.41 μg/L (n = 10) and 17.0 ± 6.1 μg · h/L (n = 10), respectively, and occurred on day 15. The single highest Cmax was 1.91 μg/L. At standard application rates in patients with acne vulgaris, the maximum average Cmax and AUC values of tazarotenic acid were 0.10 ± 0.06 μg/L (n = 8) and 1.54 ± 1.01 μg · h/L (n = 8), respectively, and occurred on day 15. At exaggerated application rates in patients with photodamaged skin, the maximum average Cmax and AUC values of tazarotenic acid were (mean ± SD) 1.75 ± 0.53 μg/L (n = 16) and 23.8 ± 7.0 μg · h/L (n = 16), respectively, and occurred on day 22. The single highest Cmax was 3.43 μg/L on day 29. At standard application rates in patients with photodamaged skin, the maximum average Cmax and AUC values of tazarotenic acid were 0.236 ± 0.255 μg/L (n = 8) and 2.44 ± 1.38 μg · h/L (n = 8), respectively, and occurred on day 15. Gender had no influence on the systemic exposure of tazarotenic acid. The most common treatment-related adverse events were signs and symptoms of local irritation, of mild or moderate severity. Conclusion: The pharmacokinetics of tazarotene cream 0.1% in patients with acne vulgaris or photodamaged skin are similar. The maximum average plasma concentrations of tazarotenic acid after topical application of tazarotene cream 0.1% to the face were less than 0.25 μg/L. The maximum average plasma concentrations of tazarotenic acid following application to an exaggerated body surface area (15%) were less than 1.8 μg/L.

Once‐Daily Naftifine Cream 1% in the Treatment of Tinea Cruris and Tinea Corporis

Seventy patients with tinea cruris or tinea corporis were treated with naftifine cream 1% or vehicle once daily (or 4 weeks in this double‐blind, randomized study. After two weeks, the patients using naftifine had a significantly higher mycologic cure rate than the vehicle‐treated patients (79% vs. 31 %, p < 0.001), and they showed significantly better resolution of signs and symptoms. Statistically significant differences favoring naftifine over its vehicle were found throughout the treatment period and 2 weeks posttreatment.