Plaque psoriasis of mild to moderate severity is routinely treated with topical steroids and coal tar along with emollients. A safe and convenient new treatment modality would be of value to most patients with psoriasis.
Our purpose was to evaluate the safety and efficacy of a new vitamin D3 analogue, calcipotriene, for the treatment of plaque psoriasis.
Twice-daily dosing of calcipotriene was compared with its vehicle, for up to 8 weeks, in a double-blind study of 277 patients at 10 study centers in the United States. Two hundred forty-seven patients completed the trial. The clinical characteristics of plaque elevation, erythema, scaling, and overall disease severity were evaluated at baseline and after 1, 2, 4, 6, and 8 weeks of treatment. A Physician's Global Assessment of improvement or worsening of the disease was performed after 1, 2, 4, 6, and 8 weeks of treatment. Blood and urine samples, for routine clinical laboratory tests, were collected at baseline and after 1, 2, 4, and 8 weeks of treatment.
As early as the week 1 evaluation, patients treated with calcipotriene ointment 0.005% had significantly lower mean scores (p = 0.043) than the vehicle-treated patients for the disease characteristics of plaque elevation, erythema, and scaling. This trend continued through week 8 of treatment when 70% of the calcipotriene-treated patients showed 75% or more improvement compared with only 19% of vehicle-treated patients. Only minor treatment-related adverse events were observed. There were no abnormal laboratory results judged related to treatment and the rare instances of elevated serum calcium values were equally distributed between active and vehicle treatments.
This study provides evidence that calcipotriene is a safe, effective, and promising new agent for the treatment of moderately severe plaque psoriasis.
Plaque-type psoriasis may at times require systemic therapy. There are limited data as to whether topical calcipotriene ointment 0.005% can be used to increase the efficacy and improve the risk/benefit ratio of concurrent systemic antipsoriatic therapy.
We attempt to answer this question by means of a literature review and results of a written survey that was sent to 100 international psoriasis treatment experts.
The survey was sent to academic and psoriasis treatment center-based dermatologists who treat approximately 3000 to 4000 patients with psoriasis per month. The survey requested that dermatologists relate their experience regarding the safety and efficacy of topical, systemic, and combined topical/systemic agents in psoriasis after 8 weeks of therapy.
The results of the survey support the experience in the literature regarding the favorable use of calcipotriene ointment combined with systemic therapy for the treatment of psoriasis.
Combination therapy with calcipotriene ointment and acitretin/etretinate, cyclosporine, methotrexate, or phototherapy usually enhances efficacy while improving the risk/benefit ratio by decreasing exposure to the potentially hazardous systemic agent.
The use of corticosteroids to treat periorbital dermatoses carries significant risk of serious side effects such as glaucoma, cataracts, and blindness. Studies to assess levels of corticosteroid penetration in the eyelid are lacking.
We assessed corticosteroid penetration in eyelid skin in vitro to obtain information leading to the establishment of safer dosing regimens.
Fluticasone propionate ointment, 0.005%, was applied (approximately 2-5 mg/cm(2)) to samples of human eyelid skin, and penetration was assessed by using modified Franz diffusion cells. Drug concentration was determined at 12, 24, 36, and 48 hours after application by liquid chromatography tandem mass spectrometry.
Only very small amounts of fluticasone propionate penetrated the skin (range, 0.618% +/- 0.339% to 1.467% +/- 0.695%).
Further studies are warranted to examine the safety and efficacy of 0.005% fluticasone propionate ointment for the treatment of eyelid dermatoses.
Facial and intertriginous skin is more susceptible to corticosteroid-induced atrophy. Dosing regimens are needed for long-term management of corticosteroid-sensitive sites.
The safety and efficacy of 0.005% fluticasone propionate ointment were assessed in the short-and long-term management of moderate to severe psoriasis of facial and intertriginous areas compared with nonfacial, nonintertriginous areas.
Affected areas in 20 patients with psoriasis were treated twice daily for 2 weeks, then once daily for 2 consecutive days every week for 8 more weeks.
More than 50% improvement occurred after 2 weeks (day 15) in 100% of facial and intertriginous lesions and was maintained during long-term therapy in more than 85% of facial and intertriginous lesions. More than 50% improvement for nonfacial, nonintertriginous areas reached only 80% by day 15. Recurrence rates for facial and intertriginous areas were lower than in the nonfacial, nonintertriginous areas. Skin atrophy and telangiectasia did not occur. Facial and intertriginous sites responded more quickly to topical fluticasone propionate ointment than nonfacial, nonintertriginous skin.
Limited application of fluticasone propionate ointment over a period of 10 weeks is effective and delays lesion recurrence without causing skin atrophy in patients with moderate to severe psoriasis in areas at risk for corticosteroid application, such as facial and intertriginous areas.
Fluocinolone acetonide 0.01% in a blend of refined peanut and mineral oils has been used as treatment for scalp psoriasis for several years, but only more recently for atopic dermatitis.
We sought to study the effectiveness for atopic dermatitis, potential for adrenal axis suppression, and safety of the fluocinolone acetonide 0.01% in oil in children with atopic dermatitis, including children with atopic dermatitis and peanut allergic sensitivity.
Three separate studies were performed in children aged 2 to 12 years with atopic dermatitis: multicenter double-blind, randomized, and vehicle-controlled trial; cortisol stimulation testing; and prick testing, patch testing, and monitored medication use in children with peanut allergic sensitivity.
Improvement of >/=50% was demonstrated within 2 weeks in 81% to 87% of 81 patients treated with active medication versus 39% of 45 children treated with vehicle oil alone. No adrenal suppression occurred after 4 weeks of therapy in 32 patients. None of 9 patients who were peanut sensitive reacted to either the full formulation or vehicle in prick or patch testing; 20 children who were peanut sensitive showed no allergic reactions after application of the medication.
Fluocinolone 0.01% in peanut oil is an effective alternative to the use of topical corticosteroid agents in ointment, cream, and lotion forms in children. No evidence of adrenal suppression or adverse local effects were demonstrated in these studies. The medication was well tolerated in patients with peanut allergic sensitivity.
Solar lentigines are a chronic condition of the aging population resulting from years of cumulative sun exposure. A topical treatment that is both safe and effective would be welcome and useful. Combinations of therapeutic agents are often used and allow synergy of mechanisms with tolerability. A tyrosinase inhibitor in use in Europe, 4-hydroxyanisole (Mequinol), and the retinoid tretinoin have been used singly as depigmenting agents.
The efficacy and safety of the combination product of 2% 4-hydroxyanisole (4HA [mequinol]) /0.01% tretinoin solution (tradename Solagé) were evaluated in two phase III, randomized, controlled, double-blind trials.
Subjects were randomized to treatment with 4HA/tretinoin solution, one of the active components (4HA or tretinoin), or vehicle. Subjects applied the test solution with a wand applicator twice daily to all solar lentigines and related hyperpigmented lesions on the face, forearms, and backs of hands for up to 24 weeks. Trial 1 had a 24-week no-treatment regression phase and trial 2 had a 4-week no-treatment regression phase. Information collected included clinical assessments of Target Lesion Pigmentation, Physician's Global Assessment of Improvement/Worsening, an Assessment of Overall Cosmetic Effect, and a Subject's Self-Assessment Questionnaire.
The 4HA/tretinoin combination was clinically superior to each of its active components and to the vehicle in the treatment of solar lentigines. At the end of treatment, in trial 1 and trial 2, 4HA/tretinoin was statistically superior to each of its active components and vehicle on the forearms and face (P </=.03), except versus tretinoin on the face in trial 2 (P =.2). In trial 2, a trend toward greater efficacy of 4HA/tretinoin over tretinoin on the face was demonstrated at the end of treatment (P =.2), which was also increasingly evident at the end of the 4-week follow-up (P =.06). Most skin-related adverse events were mild and were similar for both the 4HA/tretinoin and tretinoin treatment groups.
For the treatment of solar lentigines and related hyperpigmented lesions, the topical combination product containing 2% 4HA/0.01% tretinoin solution is well tolerated and superior to either active component.
Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris.
We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris.
A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products.
A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p < 0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported.
The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.
Preclinical study and human patch tests indicate polyolprepolymer-2 may reduce cutaneous tretinoin-induced irritation.
This study compared the clinical efficacy and safety of a 0.025% tretinoin cream containing polyolprepolymer-2 and its vehicle to a commercially-available 0.025% tretinoin cream.
In this 12-week multicenter, double-blind, parallel group study in patients with mild to moderate acne, objective lesion counts and the investigators' global evaluations evaluated efficacy. Subjective evaluations of skin irritation were used to study safety.
A total of 271 patients were enrolled. The active treatments demonstrated comparable efficacy that was statistically significantly greater than that of the vehicle. Safety evaluations of cutaneous and noncutaneous adverse events also indicated comparable results of the active treatments.
The commercially-available 0.025% tretinoin cream and the 0.025% tretinoin cream containing polyolprepolymer-2 demonstrated comparable efficacy and safety.
Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris.
The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris.
Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus.
Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed.
Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.
There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis.
Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis.
Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period.
All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring.
Local skin responses may have suggested active treatment to investigators.
Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.
Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris.
We compared the skin tolerance of adapalene 0.1% gel with tretinoin 0.025% gel in subjects with acne.
Fifteen acne patient volunteers were enrolled in this investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Adapalene 0.1% gel and tretinoin 0.025% gel were applied once a day to one half-face by the volunteers for 14 consecutive days. Clinical signs (erythema, desquamation, papules, vesicles, edema) and subjective symptoms (tightness, pruritus, burning) were evaluated and scored daily except on weekends.
Adapalene 0.1% gel was better tolerated than tretinoin 0.025% gel. The overall mean score calculated from all features combined was significantly higher with tretinoin gel than with adapalene gel (p = 0.002).
Adapalene 0.1% gel was significantly less irritating than tretinoin 0.025% gel when tested in acne patients.
The addition of polyolprepolymer-2 in tretinoin formulations may reduce tretinoin-induced cutaneous irritation.
This study compared the efficacy and safety of a new 0.025% tretinoin gel containing polyolprepolymer-2, its vehicle, and a commercially-available 0.025% tretinoin gel in patients with mild to moderate acne vulgaris.
In this 12-week multicenter, double-blind, parallel group study, efficacy was evaluated by objective lesion counts and the investigators' global evaluations. Subjective assessment of cutaneous irritation by the investigators and patients evaluated safety.
The efficacy of the two active treatments in this 215 patient study was comparable, and both treatments were statistically significantly more effective than vehicle. When compared with the commercially-available tretinoin gel, the formulation containing polyolprepolymer-2 demonstrated statistically significantly less peeling at days 28, 56, and 84, statistically significantly less dryness by day 84, and statistically significantly less itching at day 14. Irritation scores for the formulation containing polyolprepolymer-2 were numerically lower but not statistically different from those of the commercially-available gel for erythema and burning. The number of cutaneous and noncutaneous adverse events were similar for both active medications.
The two 0.025% gels studied demonstrated comparable efficacy. However, the gel formulation containing polyolprepolymer-2 caused significantly less peeling and drying than the commercially-available formulation by day 84 of the study.
To evaluate pimecrolimus cream 1% and tacrolimus ointment 0.03% in pediatric patients with moderate atopic dermatitis (AD).
141 patients (aged 2-17 years) were randomized to treatment with pimecrolimus cream 1% (n=71) or tacrolimus ointment 0.03% (n=70) twice daily for 6 weeks.
At day 4, local, application-site reactions were less common and of shorter duration with pimecrolimus than with tacrolimus. Incidence of erythema/irritation was 8% (6/71) with pimecrolimus compared with 19% (13/70) with tacrolimus (P=.039). Fewer patients receiving pimecrolimus (0%, 0/6) experienced erythema/irritation lasting >30 minutes, compared with those receiving tacrolimus (85%, 11/13; P <.001). Fewer patients reported itching with pimecrolimus (8%; 6/71) than with tacrolimus (20%; 14/70; P=.073). Incidence of warmth, stinging, and burning was similar in both groups; however, reactions lasting >30 minutes were fewer with pimecrolimus (0%, 0/14) than with tacrolimus (67%, 8/12; P <.001). More patients receiving pimecrolimus rated ease of application as 'excellent' or 'very good', compared with tacrolimus (76% vs 59%, respectively; P <.020). Efficacy was similar in both groups at day 43. Both treatments were generally well tolerated with no unexpected adverse events.
Pimecrolimus cream 1% had better formulation attributes and local tolerability than tacrolimus ointment 0.03% while providing similar efficacy and overall safety in pediatric patients with moderate AD.
Tacrolimus ointment is approved for the treatment of moderate to severe atopic dermatitis (AD). We sought to evaluate the efficacy and safety of tacrolimus ointment 0.03% compared with vehicle in the treatment of patients with mild to moderate AD.
Two identically designed, independent, randomized, double-blind, 6-week studies--one pediatric and one adult--in patients with mild to moderate AD were conducted. Combined data from 617 patients were used in the analysis. The primary efficacy end point was percentage of patients with treatment success (defined as "clear" or "almost clear" on the Investigator's Global AD Assessment) at end of study.
As early as day 4, treatment success occurred in 17.7% of patients treated with tacrolimus compared with 9.8% of patients treated with vehicle ( P = .003), and by study end had increased to 49.7% for tacrolimus versus 29.0% for vehicle (P < .0001). Tacrolimus was associated with significantly less application site pruritus than vehicle (29.0% vs 37.5%; P = .03). There was no difference between tacrolimus and vehicle in the incidence of application site skin burning and stinging.
Tacrolimus ointment 0.03% is effective and safe for the management of mild to moderate AD in both adult and pediatric patients, and has a rapid onset of action.
Treatment with clobetasol propionate 0.05% cream is effective against lichen sclerosus et atrophicus (LSA) of the vulva.
The purpose of this study was to retrospectively evaluate whether clinical and histologic responses to topical clobetasol can be accomplished in penile LSA.
A self-assessment questionnaire was obtained from 22 men with LSA, and a clinical examination was performed in 21 of them. Biopsy specimens from 15 cases were compared before and after treatment.
Itching, burning, pain, dyspareunia, phimosis, and dysuria decreased significantly (P < .001 to .05) after 1 to 2 daily applications, for a mean of 7.1 weeks (2-16 weeks). Additional operation for phimosis was required in 6 of the 22 men. All histologic LSA criteria were significantly (P < .01 to .05) reduced after treatment.
Topical treatment of penile LSA with clobetasol propionate represents a safe and effective therapy with no risk of epidermal atrophy but with some potential for triggering latent infections, most importantly human papillomavirus.
Desonide 0.05% was recently developed in an emulsion foam formulation.
The safety of desonide foam 0.05% in children aged 3 months to 17 years was evaluated in two phase II studies and one phase III study.
A phase II open-label study of the effect of desonide foam 0.05% on the hypothalamic-pituitary-adrenal axis was evaluated in pediatric and adolescent participants with mild-to-moderate atopic dermatitis. The phase II and III clinical efficacy studies evaluated adverse events.
At the end of the 4-week treatment in the phase II study, 4% (3 of 75) of participants experienced mild, reversible hypothalamic-pituitary-adrenal-axis suppression. The combined safety data from the phase II and III studies revealed 6% of participants in the desonide foam group and 14% in the vehicle foam group reported adverse events (P = .0002), with application site burning as the most commonly reported adverse event (3% in the desonide foam group vs 7% in the vehicle foam group; P = .004).
The studies evaluated short-term use only.
Desonide foam was safe and well tolerated in participants as young as 3 months.
The efficacy and safety of clobetasol propionate 0.05% scalp application was evaluated in 378 patients with moderate to severe scalp psoriasis in a double-blind vehicle-controlled parallel group study. After 2 weeks of twice-daily applications, 81% receiving active drug versus 22% receiving vehicle had clearing of 50% or greater. Complete clearing was seen in 26% with active drug and 1% with vehicle. Local side effects were primarily burning or stinging in 11% and 10% of patients treated on an active or a vehicle regimen, respectively. The morning cortisol levels of 168 patients were checked at baseline and again after 2 weeks of drug therapy. Subnormal morning plasma cortisol values were seen in 5% of the patients receiving active drug and in 5% receiving vehicle; 13% of those taking active drug versus 5% taking vehicle had a 50% or greater decrease in morning cortisol at the 2-week visit compared with baseline values. Clobetasol propionate 0.05% scalp application appears to be a safe and an effective treatment for scalp psoriasis.
The potential systemic availability of retinoids from topically applied isotretinoin was assessed in 12 men with acne vulgaris. Isotretinoin 0.05% gel was applied to patients at a daily dose of 20 gm (equivalent to 10 mg of isotretinoin) over a 1900 cm2 surface area of skin on the face, back, and chest for 30 days. Blood samples were collected throughout the study and up to 48 hours after the last topical application; they were assayed for isotretinoin, tretinoin, and 4-oxo-isotretinoin by specific high-performance liquid chromatography. Plasma concentrations of isotretinoin, tretinoin, and 4-oxo-isotretinoin were not measurable (less than 20 ng/ml) at any time. Most adverse experiences were cutaneous; a few systemic adverse experiences were judged to be remotely related to topical drug administration. The lack of measurable plasma concentrations of isotretinoin, tretinoin, or 4-oxo-isotretinoin and systemic adverse experiences indicates negligible systemic availability of retinoids even after multiple application of isotretinoin 0.05% gel at doses approximately 12 times greater than normal daily use.
Clobetasol propionate 0.05% emulsion foam was recently developed for use on multiple body sites.
We sought to evaluate safety and efficacy of clobetasol emulsion foam 0.05% to treat steroid-responsive dermatoses in multiple age groups.
A phase II open-label study evaluated the effect of clobetasol foam on the hypothalamic-pituitary-adrenal axis in 52 participants aged 6 years or older with mild-to-severe atopic dermatitis (AD). Cosyntropin stimulation test was used to determine the effect of clobetasol foam on hypothalamic-pituitary-adrenal axis, with a normal response considered to be a postinjection serum cortisol level greater than 18 mug/dL. Another phase II open-label pharmacokinetic safety study was conducted in 32 participants aged 12 years or older with mild-to-moderate plaque-type psoriasis. Pharmacokinetic parameters evaluated included maximal plasma concentration of clobetasol propionate, time to achieve maximum concentration, and area under the curve. Two phase III, randomized controlled studies assessed treatment success in participants aged 12 years or older with moderate-to-severe AD (N = 377) or mild-to-moderate plaque-type psoriasis (N = 497). In all studies, participants received study drug for 2 weeks. In the AD study, treatment success was determined using a composite end point requiring an Investigator's Static Global Assessment (ISGA) score of 0 or 1, erythema score of 0 or 1, induration/papulation score of 0 or 1, and improvement in the ISGA score of at least two grades from baseline. Likewise, the study in plaque-type psoriasis used a composite end point requiring an ISGA score of 0 or 1, erythema score of 0 or 1, scaling score of 0 or 1, plaque thickness score of 0, and improvement in the ISGA score of at least two grades from baseline.
Significantly more participants achieved treatment success on clobetasol foam than vehicle foam (P < .0001 and P = .0005 for each study). Reversible hypothalamic-pituitary-adrenal axis suppression was observed in 27% of participants aged 18 years or older and 47% in participants aged between 6 and younger than 12 years, but 0% in participants aged between 12 and younger than 18 years.
The studies evaluated short-term use only.
Clobetasol emulsion formulation foam is safe and effective for treatment of moderate-to-severe AD and mild-to-moderate plaque-type psoriasis in patients aged 12 years or older.
Topical corticosteroids are useful for the treatment of pediatric dermatoses. However, concerns regarding possible systemic and topical toxicities have limited the use of moderate-potency corticosteroids in children.
Our purpose was to characterize the safety of fluticasone propionate cream in children.
Children between 3 months and 5 years 11 months (n = 32) and 3 up to 6 years of age (n = 19) with moderate to severe atopic dermatitis (> or =35% body surface area; mean body surface area treated, 64%) were treated with fluticasone propionate cream, 0.05% twice daily for 3 to 4 weeks. Serum cortisol response, fluticasone levels, skin changes, and adverse events were analyzed.
Mean cortisol levels were similar at baseline (13.76 +/- 6.94 microg/dL prestimulation and 30.53 +/- 7.23 microg/dL poststimulation) and at end of treatment (12.32 +/- 6.92 microg/dL prestimulation and 28.84 +/- 7.16 microg/dL poststimulation). Only 2 of 43 children had end-treatment poststimulation values less than 18.0 microg/dL. No significant adverse cutaneous effects were noted.
Fluticasone propionate cream 0.05% appears to be safe for the treatment of severe eczema for up to 4 weeks in children 3 months of age and older.
A novel lotion formulation of fluticasone propionate 0.05% has recently become available. Two large, randomized, placebo-controlled, double-blind studies involving 438 subjects demonstrated its efficacy and safety when applied once daily in the treatment of atopic dermatitis in subjects from 3 months to 87 years of age. The studies were limited to 4 weeks duration of use of fluticasone lotion and did not assess longer term efficacy or side effects.
Tazarotene in a gel formulation is widely used in the treatment of psoriasis.
To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis.
A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period.
Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation.
Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream.
We studied the effectiveness of clobetasol propionate ointment 0.05% in experimentally induced Rhus dermatitis. Clobetasol rapidly decreased the vesiculation at each treated site, although the effect was most prominent at the site to which clobetasol was applied the earliest, that is, at 12 hours after exposure to Rhus extract. On the basis of this experimental model, clobetasol propionate ointment 0.05% may be effective therapy for naturally occurring Rhus dermatitis.
In a double-blind, parallel-group, multicenter trial in 134 patients with severe, localized, plaque psoriasis, the success rate (described as "healed" or "marked improvement") at the end of the study was 96% in the halobetasol propionate group and 91% in the clobetasol propionate group. A significantly larger proportion of patients treated with halobetasol had no disease or mild disease after 14 days compared with those treated with clobetasol (86% versus 70%, p = 0.023). Healing within 24 days of starting treatment was noted in 69% and 56% of patients treated with halobetasol and clobetasol, respectively. Adverse effects were reported in a smaller percentage of patients treated with halobetasol propionate ointment than in those treated with clobetasol propionate ointment (7% versus 12%). Cosmetic acceptability and ease of application were recorded as "very good" in a larger percentage of patients treated with halobetasol propionate ointment than in the group treated with clobetasol propionate (90% versus 80%).
In a double-blind, parallel-group, multicenter comparative trial in 127 evaluable patients with chronic, localized atopic dermatitis or lichen simplex chronicus, healing was reported in a higher percentage of patients treated with halobetasol propionate ointment than in those in the clobetasol propionate treatment group (65.1% versus 54.7%). The success rates (described as "healed" and "marked improvement") were practically identical in the two treatment groups (93.7% versus 92.2%). Early onset of therapeutic effect, that is, within 3 days of the start of treatment, was similar in the two treatment groups (24% versus 28%). Both preparations were well tolerated. Adverse effects were reported in 5% and 2% of the patients treated with halobetasol propionate and clobetasol propionate ointments, respectively.
Fluticasone propionate is a novel and potent corticosteroid. It seems to have an improved therapeutic index on the basis of studies on skin thinning and suppression of hypothalamic-pituitary-adrenal axis.
We assessed the efficacy and safety of fluticasone propionate (FP) 0.05% cream once daily as compared with clobetasone butyrate (CB) 0.05% cream twice daily in children with atopic dermatitis (AD).
Twenty-two children (3 to 8 years old) with moderately active AD received either FP once daily or CB twice daily. Severity of AD was scored weekly by means of the modified Scoring of Atopic Dermatitis system (SCORAD) and treatment was either stopped when skin lesions were almost cleared (SCORAD < 9) or after 4 weeks. Cortisol excretion was determined by means of 24-hour urine before and after treatment.
Twenty-one children completed the study. After 1 week of treatment, mean SCORAD significantly decreased in both treatment groups. After 2, 3, and 4 weeks cumulatively, 8, 12, and 16 children, respectively, were clinically healed (SCORAD < 9). No significant differences in efficacy were observed between the two treatments. Urinary cortisol excretion was not altered by either of the treatments. Two weeks after discontinuation of active treatment, mean SCORAD had increased to 22, but still was significantly lower than that at the beginning of the study.
Once-daily treatment with FP is as safe and effective as twice-daily treatment with CB in children with AD. All children experienced an exacerbation of AD within 2 weeks after treatment was withdrawn, indicating the need for long-term "intermittent" treatment.
Vulvar lichen sclerosus is a chronic condition usually responsive to topical corticosteroids.
We sought to evaluate the efficacy (reduction of signs and symptoms) and safety of clobetasol propionate 0.05% and tacrolimus 0.1% in the treatment of vulvar lichen sclerosus.
This double-blind, randomized study comparing 2 treatments over a 3-month period, enrolled 58 female patients with newly diagnosed vulvar lichen sclerosus or untreated vulvar lichen sclerosus for at least 1 month.
In all, 55 patients were included in the statistical analysis. A total of 28 patients were assigned to the tacrolimus group and 27 patients to the clobetasol group. Both groups showed a significant difference in the decrease of symptoms and signs of lichen sclerosus. At the end of the study, 28 participants (19 tacrolimus and 9 clobetasol) still had some clinical signs of lichen sclerosus (χ(2) = 6.56, P = .015). However, a significantly higher number of patients in the clobetasol group (n = 15) had absence of signs and symptoms of lichen sclerosus (χ(2) = 10.35, P = .002; χ(2) = 10.35, P = .002). No adverse events were reported.
Short length of trial and recruitment through our vulvar disease referral center are limitations.
This study showed that topical clobetasol propionate was significantly more effective in treating vulvar lichen sclerosus than topical tacrolimus.
The efficacy and safety of 0.05% halobetasol propionate ointment were evaluated in patients with chronic atopic or other eczematous dermatoses in two vehicle-controlled, double-blind studies: a paired-comparison study in 124 patients (study A) and a parallel-group study in 100 patients (study B). In study A, patients applied both treatments twice daily for 2 weeks and were evaluated by investigators on days 0, 7, and 14 with 0 to 3 severity scales and by self-assessment with two 5-step end-of-treatment rating scales. In study B, patients applied treatments twice daily for 2 weeks, and investigators made evaluations on days 0, 3, 7, and 14 with 0 to 6 scales and also made a 5-step end-of-treatment physician's global assessment. In study A, both severity scores and patient ratings favored halobetasol propionate significantly on days 7 (p less than or equal to 0.0013) and 14 (p less than 0.0001); in study B, severity scores on days 3 (p less than or equal to 0.045, pruritus, erythema, and overall lesion severity), 7, and 14 (p less than 0.001, all comparisons) also favored halobetasol propionate significantly, and global assessments showed complete resolution or marked improvement for 83% of patients using halobetasol propionate versus 28% of those using vehicle (p less than 0.0001). No instances of systemic effects or skin atrophy were reported in either study. We conclude that 0.05% halobetasol propionate ointment is highly effective and well tolerated in the treatment of the conditions studied, with the rapid action and high degree of clearing associated with superpotent corticosteroid formulations.
In a double-blind, parallel-group, multicenter comparative trial in 84 evaluable patients with severe, localized plaque psoriasis, 0.05% halobetasol propionate ointment proved significantly superior (p = 0.02) to 0.1% betamethasone valerate ointment with respect to the success rate, as indicated by ratings of "healed" or "marked improvement" (88.1% versus 64.3%). The therapeutic effect was observed within 5 days of the start of treatment in 76% and 67% of the patients treated with halobetasol propionate and betamethasone valerate ointments, respectively. Both preparations were well tolerated. Minor adverse effects at the site of application were reported in only 2% of the patients in each treatment group. Neither skin atrophy nor systemic adverse effects were observed.
In a double-blind, parallel-group, multicenter comparative trial on 104 evaluable patients with severe, localized plaque psoriasis, 0.05% halobetasol propionate ointment demonstrated an 88.7% success rate assessed as "healed" or "marked improvement" compared with 78.5% for 0.05% betamethasone dipropionate ointment. Healing was observed within 24 days of the start of treatment in 40% and 25% of the patients who received halobetasol propionate and betamethasone dipropionate ointments, respectively. After 4 weeks' treatment, tolerability of both ointments was good. Neither skin atrophy nor systemic adverse effects were observed. Patient acceptance of halobetasol propionate ointment, based on cosmetic acceptability and ease of application, was significantly better (p = 0.02) than that of betamethasone dipropionate ointment.
It was discovered that Skin Cap (Cheminova Internacional S.A., Madrid, Spain), an over-the-counter psoriasis therapy with zinc pyrithione, contained clobetasol propionate and it was withdrawn from the market by the US Food and Drug Administration review. Some suggested that there might be a synergistic effect of zinc pyrithione with clobetasol propionate.
We sought to evaluate the efficacy of clobetasol propionate 0.05% foam with and without the coadministration of a topical 0.25% zinc pyrithione spray in treating psoriasis involving sites other than the scalp.
We conducted a randomized, double-blind, right/left study of patients with mild to moderate, generally symmetric, plaque-type psoriasis. Patients were assigned to treatment with clobetasol propionate foam on all psoriatic lesions and then randomly assigned to use zinc pyrithione spray to either the right or left side of their body (vehicle spray to be applied to the opposite side). There was a 2-week treatment phase (visits at baseline, week 1, and week 2) and a follow-up phase (visit at week 4), and all treatments were administered twice daily for 2 weeks. The primary outcome measure was the change from baseline to week 2 in the composite score of the signs of psoriasis (erythema, scaling, plaque thickness) for symmetric target lesions.
A total of 25 patients were enrolled; 24 completed the trial and 1 was lost to follow up. Of those who completed the study, 63% (15 of 24) were men, and the mean age (+/-SD) was 50 years (+/-12.2). After 2 weeks of therapy, the average decline in the composite score was 3.5 (+/-1.8) for monotherapy (clobetasol propionate foam and vehicle) and, similarly, 3.3 (+/-1.8) for clobetasol propionate foam plus zinc pyrithione spray (P =.5).
Zinc pyrithione spray does not appear to enhance the efficacy of clobetasol propionate foam after 2 weeks of therapy.
Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children.
Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopic dermatitis.
One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration.
No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment (p < 0.05).
Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months.
Two hundred sixty-eight patients with mild to moderate acne vulgaris completed a multicenter, double-blind, controlled study comparing isotretinoin 0.05% gel with its vehicle. Patients were treated twice daily for up to 14 weeks. Efficacy was measured by counting facial inflammatory and noninflammatory lesions and by grading acne severity initially and at 2- to 3-week intervals throughout the study. The isotretinoin 0.05% gel proved to be statistically more effective than vehicle in reducing inflammatory lesions after 5 weeks and in reducing noninflammatory lesions and acne severity grade after 8 weeks. Except for two patients who dropped out because of irritation, isotretinoin 0.05% gel was well tolerated.
Efficacy of topical steroids in alopecia areata is still discussed.
The purpose of this study was to evaluate the efficacy of clobetasol propionate 0.05% ointment under occlusion in 28 patients with alopecia areata totalis (AT) or AT/alopecia universalis.
A total of 28 patients were instructed to apply 2.5 g of clobetasol propionate to the right side of the scalp every night under occlusion with a plastic film. Treatment was performed 6 days a week for 6 months. When regrowth of terminal hair occurred, treatment was extended over the entire scalp. All patients were followed up for another 6 months.
Of the 28 patients included in the study, 8 were treated successfully (28.5%). Regrowth of terminal hair began on the treated side 6 to 14 weeks after the start of treatment. Of these 8 patients, 3 had a relapse and were not able to maintain hair regrowth.
Our study shows that clobetasol propionate 0.05% under occlusion is effective in inducing hair regrowth in patients with AT or AT/alopecia universalis. Occurrence of hair regrowth only on the treated half of the scalp clearly shows that efficacy of treatment is a result of a local and not systemic effect of the drug. Although only 17.8% of patients had long-term benefit by treatment, our results were obtained in a population of patients with severe and refractory forms of the disease.
Six investigators evaluated 0.05% halobetasol propionate cream and its vehicle in 111 patients with chronic atopic dermatitis and several other eczematous dermatoses. Patients applied treatment twice daily to bilateral lesions for 14 days. Investigators graded pruritus, erythema, scaling, papulation, and lichenification using 4-point severity scales on days 0, 7, and 14. On day 14 patients provided an assessment of efficacy for both treatments. Statistically significant differences favoring halobetasol propionate over the vehicle were seen for all signs and symptoms (p less than 0.001). Substantial improvements were achieved by the active treatment by day 7 (p less than 0.001). Patients assessments of efficacy were significantly higher for halobetasol cream than for vehicle (p less than 0.001). No instances of systemic effects or skin atrophy were reported and adverse experiences were limited to burning or stinging and other minor, nonspecific complaints distributed uniformly between active treatment and vehicle. These results demonstrate that 0.05% halobetasol propionate cream is highly effective in the treatment of atopic dermatitis and other eczematous dermatoses.
In a double-blind, parallel-group, multicenter, comparative trial in 120 evaluable patients with chronic, localized atopic dermatitis or lichen simplex chronicus, the success rate (described as "healed" and "marked improvement") was 91.5% in patients treated with halobetasol propionate ointment and 83.6% in those in the diflucortolone valerate treatment group. Of patients treated with halobetasol propionate ointment, 40.7% reported healing within 17 days, whereas of those in the diflucortolone valerate treatment group, 32.8% reported healing within that time. Early onset of therapeutic effect, that is, within 3 days of the start of treatment, was reported in a higher percentage of patients treated with halobetasol propionate ointment than in those treated with diflucortolone valerate ointment (70% versus 59%). Adverse effects at the site of application were less frequently reported in patients belonging to the halobetasol propionate treatment group than in those treated with diflucortolone valerate ointment (3% versus 8%).
Betamethasone oral mini-pulse (OMP) therapy has been used effectively and safely in vitiligo, alopecia areata, and lichen planus.
We sought to evaluate the efficacy and safety of betamethasone OMP in patients with symptomatic moderate to severe oral lichen planus and to compare it with topical triamcinolone acetonide.
In all, 49 patients with moderate to severe oral lichen planus were randomly allocated to receive either OMP comprising 5 mg of betamethasone orally on 2 consecutive days per week (group A) or triamcinolone acetonide (0.1%) paste application thrice daily (group B), for 3 months followed by stepwise tapering during the next 3 months. Treatment response was assessed by the change in the score, which was based on the number of sites involved and the area affected. The changes in the symptoms and side effects were also recorded. Patients were followed up after treatment for 3 months to look for relapse.
In all, 23 of 25 patients in group A and 23 of 24 patients in group B completed the study. Good to excellent response was seen in 17 of 25 (68.0%) patients in group A as compared with 16 of 24 (66.0%) in group B at 6 months. Symptom-free state was achieved in 13 of 25 (52%) patients in group A and 12 of 24 (50%) in group B. The difference in the mean scores within each group was statistically significant from the fourth week onward in group A and eighth week onward in group B, whereas in patients with erosive disease it was second and twelfth week onward, respectively. The difference in the treatment response between the two groups was statistically significant only at week 24 when reduction in severity score was more in triamcinolone group. Side effects were seen in 14 (56%) patients in group A and 6 (25%) patients in group B, which were mild and reversible. Relapse occurred in 9 of 23 (39.1%) patients in group A after 13.78 +/- 6.96 weeks as compared with 5 of 23 (21.7%) in group B after 19.20 +/- 1.79 weeks.
The study was not blinded and the change in the quality of life with treatment was not measured.
Betamethasone OMP improves the clinical outcome in patients with moderate to severe oral lichen planus. When compared with topical triamcinolone acetonide it is equally effective but the response is earlier, especially in erosive disease. It may be a useful and convenient alternative either as a monotherapy or to achieve rapid symptomatic relief during periods of exacerbations.
This multicenter, randomized, investigator-blinded study compared the efficacy and tolerability of a combination of lymecycline 300 mg/day orally and adapalene topical gel 0.1% (n = 118) to lymecycline 300 mg/day orally plus vehicle gel (n = 124) in patients with moderate to moderately severe acne vulgaris with both inflammatory and noninflammatory lesions. The primary efficacy end point, total lesion count at end point (last observation carried forward), showed a statistically significant difference in favor of the lymecycline plus adapalene group (P =.0011). The mean decrease in total, inflammatory and noninflammatory lesion counts was significantly greater at end point in the lymecycline plus adapalene group than in the lymecycline plus vehicle group (P <.01). In addition, a significant difference for inflammatory and total acne lesions was seen sooner in the adapalene plus lymecycline group. In total, 75.5% of patients in the lymecycline plus adapalene group were markedly improved, almost clear or clear of their lesions at week 12, compared with 51.8% of those in the lymecycline plus vehicle group (P <.001). Local cutaneous tolerance was generally good in both groups, although more patients receiving the lymecycline plus adapalene combination experienced cutaneous reactions than those receiving lymecycline plus vehicle. There are relatively few studies comparing the efficacy of combined oral and topical therapy with either individual therapy alone. This study clearly demonstrates that lymecycline plus adapalene combination treatment resulted in a significantly greater mean decrease in the number of inflammatory, noninflammatory and total lesions than lymecycline plus vehicle and was well tolerated.
Previous studies indicate that tazarotene is efficacious in reducing signs of photodamage. Objective We sought to confirm the efficacy and tolerability of tazarotene 0.1% cream in the treatment of facial photodamage.
A total of 568 patients with at least moderate fine wrinkling or mottled hyperpigmentation applied tazarotene 0.1% cream or vehicle cream to their face once daily for 24 weeks.
Tazarotene cream was significantly more effective than vehicle in reducing fine wrinkles, mottled hyperpigmentation, lentigines, irregular depigmentation, apparent pore size, elastosis, tactile roughness, and an overall integrated assessment of photodamage. Significance was achieved as early as week 2 for some parameters and had not plateaued by week 24. The majority of patients reported improvements in their photodamage as early as week 4. Adverse events were predominantly mild or moderate signs or symptoms of skin irritation.
Once-daily tazarotene 0.1% cream is effective in ameliorating multiple signs of facial photodamage.
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.
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.
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.
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.
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.