Tretinoin microsphere gel 0.1% for photodamaged facial skin: a placebo-controlled trial.

Tretinoin microsphere gel (TMG) 0. 1% was evaluated as a treatment of photodamaged skin. The study included a 6-month, randomized, double-blinded, placebo-controlled phase and an additional 6-month open-label phase during which all subjects received TMG 0. 1%. Forty-five subjects with moderate to severe photodamaged facial skin applied study gel topically to the face once nightly (22 subjects received TMG 0.1% and 23 subjects received placebo). At 6 months, TMG 0. 1% was found to be superior to placebo in improving overall severity of photodamage (P=.0003) and in the investigator's global assessment of clinical response (P<.0001). Statistically significant improvement relative to placebo was observed in fine wrinkling (P<.0001), mottled hyperpigmentation (P=.0002), yellowing/ sallowness (P<.0001), and lentigines (P=.0054). The improvements observed after 6 months of open-label therapy were consistent with the results observed in TMG 0. 1%-treated subjects during double-blinded treatment. Most signs and symptoms of cutaneous irritation were mild throughout the treatment period. At one month, a higher proportion of subjects in the TMG 0. 1% group relative to the placebo group experienced an increase in severity of cutaneous irritation. After 6 months, the difference between treatment groups was statistically significant only for peeling (P=.001) and dryness (P=.007).

Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial.

BACKGROUND: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition. OBJECTIVE: The objective of the study was to determine the long-term safety and efficacy of tretinoin emollient cream 0.05% in the treatment of moderate to severe facial photodamage. METHODS: A total of 204 subjects were treated with tretinoin or placebo (vehicle emollient cream) applied to the entire face once a day for up to 2 years. Clinical and histologic effects were assessed at regularly scheduled clinic visits. RESULTS: Treatment with tretinoin resulted in significantly greater improvement relative to placebo in clinical signs of photodamage (fine and coarse wrinkling, mottled hyperpigmentation, lentigines, and sallowness), overall photodamage severity, and investigator's global assessment of clinical response (p<0.05). Histologic evaluation showed no increase in keratinocytic or melanocytic atypia, dermal elastosis, or untoward effects on stratum corneum following treatment with tretinoin compared with placebo. Immunohistochemistry studies, conducted at three study centers, showed a significant increase relative to placebo in facial procollagen 1C terminal, a marker for procollagen synthesis, at month 12 (p=0.0074). CONCLUSION: Long-term treatment with tretinoin emollient cream 0.05% is safe and effective in subjects with moderate to severe facial photodamage.

Clobetasol propionate lotion, an efficient and safe alternative to clobetasol propionate emollient cream in subjects with moderate to severe plaque-type psoriasis.

BACKGROUND: Various formulations of clobetasol propionate are currently used to treat psoriasis due to its anti-inflammatory, anti-pruritic, vasoconstrictive and immunomodulating properties. OBJECTIVE: To assess the efficacy, safety and remission profile of clobetasol propionate lotion compared to that of clobetasol propionate emollient cream and lotion vehicle in subjects with moderate to severe plaque-type psoriasis. METHODS: Multicentre, investigator-blind, randomized, active- and vehicle-controlled, parallel-group study. RESULTS: A total of 192 subjects were treated: 82 with clobetasol propionate lotion, 81 with clobetasol propionate cream and 29 with the vehicle. Clobetasol propionate lotion was significantly more effective than vehicle lotion and was comparable in efficacy to the emollient cream after 4 weeks of treatment. Treatment success was higher for subjects in the clobetasol propionate lotion group than in the emollient cream group after 4 weeks of a treatment-free follow-up period. Clobetasol propionate lotion was safe and well tolerated. CONCLUSION: The present study demonstrates that clobetasol propionate lotion is an efficacious, safe and well-tolerated alternative to the currently available emollient cream formulation, while showing a better remission profile after 4 weeks of treatment-free follow-up period.

Topical retinoid and antibiotic combination therapy for acne management.

The agents most commonly used in combination for the management of acne include topical retinoids and antibiotics. Topical retinoids normalize desquamation of the follicular epithelium, whereas antibiotics inhibit the growth of P. acnes and the production of free fatty acids. This therapeutic combination decreases comedogenesis, bacterial growth, and inflammation, thus targeting three of the four pathogenic factors associated with acne. Efficacy and tolerance are maximized with combination therapy, and the degree of skin irritation is minimized. Furthermore, adjunctive therapy with topical retinoids and antibiotics tends to produce results more quickly than single-agent therapy. This article will examine the individual agents used in combination for acne management, and discuss the mechanisms by which they achieve efficacy. The rationale of utilizing topical retinoids with antibiotics will be highlighted, particularly in relation to improved tolerance and reduced irritation.

A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris.

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.

Ciclopirox gel in the treatment of patients with interdigital tinea pedis.

UNLABELLED: BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis; Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum. OBJECTIVE: Two multicenter, double-blind, clinical studies compared the efficacy and safety of ciclopirox gel with that of its vehicle base in subjects with moderate interdigital tinea pedis with or without plantar involvement. METHODS: Three hundred and seventy-four subjects were enrolled and randomized to one of two treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice daily for 28 days, with a final visit up to day 50. The primary efficacy variable was Treatment Success defined as combined mycological cure and clinical improvement >/= 75%. Secondary measures of effectiveness were Global Clinical Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH examination and final culture result), Mycological Cure (negative KOH and negative final culture results) and Treatment Cure (combined clinical and mycological cure). RESULTS: At endpoint (final post-baseline visit), 60% of the ciclopirox subjects achieved treatment success compared to 6% of the vehicle subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of vehicle subjects were either cleared or had excellent improvement. Pooled data showed that 85% of ciclopirox subjects were mycologically cured, compared to only 16% of vehicle subjects at day 43, 2 weeks post-treatment. CONCLUSIONS: Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E. floccosum and is associated with a low incidence of minor adverse effects.

Efficacy and safety of a new triple-combination agent for the treatment of facial melasma.

Treatment of melasma, a hyperpigmentation disorder, remains a challenge. The primary objective of two 8-week, multicenter, randomized, investigator-blind studies was to compare the efficacy and safety of a hydrophilic cream formulation containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination agents tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All agents had the same drug concentration and vehicle. A total of 641 adult patients, predominantly female, with moderate to severe melasma and Fitzpatrick skin types I through IV, were randomized to the various treatment groups. Due to the similarity of the study designs, the results of the 2 studies were combined and are reported here. The primary efficacy analysis involved the proportion of intent-to-treat patients in each treatment group whose condition had completely cleared by week 8. The results of the combined clinical trials demonstrated that significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with the other treatment groups (4.6%) at the end of week 8 (P<.0001). In addition, at week 8, a 75% reduction in melasma/pigmentation was observed in more than 70% of patients treated with RA+HQ+FA compared with 30% in patients treated with the dual-combination agents. The most common adverse reactions seen with all treatment groups were erythema, skin peeling, burning, and/or stinging sensation. The majority of treatment-related adverse events were of mild severity.

Overall results of the BEST study following treatment of patients with mild to moderate acne.

In patients with acne, assurance of satisfaction with therapy is a significant factor in helping patients cope with their condition. Therefore, the BenzaClin (benzoyl peroxide/clindamycin topical gel) Efficacy and Satisfaction Trial (BEST) was developed to evaluate patient satisfaction following 8 weeks of treatment with benzoyl peroxide/clindamycin topical gel in patients with mild to moderate acne who were dissatisfied with their current acne therapy. Additional evaluations included efficacy, evaluated with the Global Acne Grading System (GAGS), and the impact of therapy on the social aspects of living with acne, measured with the Acne Quality of Life (AQOL) scale. Results demonstrated significant improvements for all study variables. Patient satisfaction, which was rated from 0 (not satisfied) to 10 (very satisfied) increased almost 3-fold from baseline to week 8 (P < or = .0001). The mean overall AQOL score also improved significantly by a mean of 2.2 points (P < .0001). Acne severity was reduced to almost half of its baseline value (measured using the GAGS score), indicating a significant treatment effect of benzoyl peroxide/clindamycin topical gel (P < or = .0001). Furthermore, as indicated by the Physician Global Assessment (PGA) performed at week 8, acne improved in 94% of patients. Improved patient satisfaction was most likely related to the significant improvements in both efficacy and quality of life (QOL). Overall results of the study suggest that benzoyl peroxide/ clindamycin topical gel is effective for the treatment of acne in patients who are dissatisfied with their current therapy.

Preliminary results of a nonrandomized, multicenter, open-label study of patient satisfaction after treatment with combination benzoyl peroxide/clindamycin topical gel for mild to moderate acne.

BACKGROUND: Assessments of patient satisfaction are needed to determine treatment-related improvement in acne from the patient's perspective. OBJECTIVES: The aims of this study were to assess patient satisfaction, drug efficacy, and the social aspects of quality of life after treatment with benzoyl peroxide/clindamycin topical gel in patients who were dissatisfied with their previous acne treatment regimens. METHODS: This nonrandomized, open-label, multicenter study was open to patients aged > or = 12 years who were dissatisfied with their previous acne treatments. Patients applied topical benzoyl peroxide/clindamycin gel twice daily for 8 weeks. Patient satisfaction was assessed on an 11-point analog scale (0 = not satisfied; 10 = very satisfied). The social effects of acne were assessed using a 9-question acne quality of life (AQOL) scale, and treatment efficacy was assessed using the global acne grading system (GAGS). Safety and tolerability were monitored continuously through self-reporting and patient questioning. RESULTS: Preliminary results were gathered for 257 patients. Relative to baseline, patients were significantly more satisfied after 8 weeks of treatment with benzoyl peroxide/ clindamycin gel (P < 0.001). The mean overall cumulative AQOL score improved significantly among 249 patients aged > or = 12 years (P < 0.001), but the clinical relevance of this finding is unknown. The mean GAGS score decreased from 15.9 (SD = 6.0) at baseline to 8.2 (SD = 5.7) at week 8 (P < 0.001). The most common adverse events were dry skin and skin irritation. CONCLUSIONS: These preliminary results suggest that patients who are dissatisfied with their current acne regimen may be more satisfied after treatment with benzoyl peroxide/clindamycin gel. However, more definitive conclusions can be drawn only following the completion of the study.

Effective treatment of actinic keratosis with 0.5% fluorouracil cream for 1, 2, or 4 weeks.

New therapeutic options would benefit patients with actinic keratosis (AK), a precancerous condition that is a significant health concern. The efficacy and safety of a microsphere-based formulation of 0.5% fluorouracil cream were evaluated in a randomized, double-blind, multicenter, parallel-group study. Patients (N= 177) were randomized to receive 0.5% fluorouracil or vehicle once daily for 1, 2, or 4 weeks. Efficacy was assessed by lesion counts and clearance. Safety was evaluated by monitoring adverse events, including facial irritation. Significant improvements were seen from baseline to posttreatment follow-up in all efficacy variables for all fluorouracil regimens compared with vehicle. Patients treated for one week experienced significant improvements compared with vehicle, although efficacy increased with increasing treatment duration. Most patients experienced mild to moderate facial irritation of predictable onset and duration. Once-daily administration of 0.5% fluorouracil cream for 1, 2, or 4 weeks is safe and effective for the treatment of AKs.