British Journal of Dermatology

No specific data are available on tacrolimus ointment as a second-line treatment in adults with facial eczema. To compare tacrolimus 0.1% and fluticasone 0.005% ointments in adults with moderate to severe atopic dermatitis (AD) of the face in whom conventional treatment was ineffective or poorly tolerated. Patients were randomized to double-blind treatment of facial AD with twice-daily tacrolimus ointment (n = 288) or fluticasone ointment (n = 280) for 3 weeks or until clearance. After day 21, patients could continue without the study treatment, apply the same ointment once daily, or switch to the other medication twice daily, depending on lesion clearance and patient/physician satisfaction. The primary endpoint was the day-21 response [> or = 60% reduction in the modified Local Eczema and Severity Index (mLEASI) score]. Secondary endpoints included facial erythema and pruritus, global clinical response, treatment switching at day 21 and safety. RESULTS Response with tacrolimus ointment (93%) was superior to that with fluticasone (88%; P = 0.026). Improvements in mLEASI components were also greater with tacrolimus ointment. Facial erythema and pruritus improved in both groups. Global clinical response was rated 'marked improvement' or better in 88% and 79% of patients in the tacrolimus ointment and fluticasone groups, respectively. At day 21, 9% of patients switched from fluticasone to tacrolimus ointment, while 4.5% switched from tacrolimus ointment to fluticasone. Adverse events were more frequent with tacrolimus ointment as a result of the higher incidence of application-site skin burning sensation. Safety of both drugs was in line with their respective summary of product characteristics. Tacrolimus 0.1% ointment has superior efficacy to fluticasone 0.005% ointment for twice-daily treatment of adults with moderate to severe facial AD in whom conventional therapy was inadequately effective or not tolerated. Tacrolimus 0.1% ointment is a safe and effective second-line treatment for the control of moderate to severe AD of the face.

Melasma is an acquired, chronic hypermelanosis for which therapy remains a challenge. To compare the efficacy and safety of a triple combination [TC: fluocinolone acetonide 0.01%, hydroquinone (HQ) 4%, tretinoin 0.05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma in Asian patients. This was a multicentre, randomized, controlled, investigator-blinded, parallel comparison study. East and South-East Asian patients aged 18 years or older, with a clinical diagnosis of moderate to severe melasma, were enrolled in this study. Patients were enrolled at baseline and treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8. The primary efficacy variable was the melasma global severity score (GSS). Other outcome measures included Melasma Area and Severity Index, global improvement and patient satisfaction. Safety was assessed through the reporting of adverse events. TC had superior efficacy to HQ for the primary variable: 77/120 patients (64.2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients (39.4%) on HQ (P < 0.001). The secondary efficacy variables confirmed these results. Patient satisfaction was in favour of TC (90/127, 70.8%, vs. 64/129, 49.6%; P = 0.005). More patients had related adverse events on TC (63/129, 48.8%) than on HQ (18/131, 13.7%) but most were mild and none was severe. Efficacy in Asians and patient satisfaction were superior with the fixed TC than with HQ 4%.

A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.

Thirty patients were entered into a double-blind trial comparing a dimethoxynaphthalene derivative (RS-43179 gel) and fluocinolone acetonide (Synalar gel) in the treatment of psoriasis. The two preparations were applied three times daily for 4 weeks, and the patients were assessed at weeks 1, 2, 3, 4, 7 and 9. No significant differences between the two preparations could be detected. By the end of the 4-week treatment period, the number of patients showing a 'Good, Excellent or Clear' therapeutic response was 25 out of 28 after RS-43179 treatment and 26 out of 28 after Synalar treatment. Four patients experienced irritation on the side treated with RS-43179. In two of these patients the reaction was severe and the treatment was discontinued, but in the other two patients, the local irritation was only moderate. No other adverse reactions were seen.

Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations. This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of <or=2 was achieved, the patient entered the disease control period (DCP) and was randomized to receive tacrolimus (n=125) or vehicle ointment (n=125) twice weekly for 12 months. Exacerbations were treated with 0.03% tacrolimus ointment twice daily until an IGA<or=2 was regained, then randomized treatment was restarted. The outcome measure was the number of DEs during the DCP that required substantial therapeutic intervention. Proactive application of 0.03% tacrolimus ointment significantly reduced the number of DEs during the DCP that required substantial therapeutic intervention (median difference: 1.0; P<0.001; Wilcoxon rank-sum test), the percentage of DE treatment days (median difference: 6.2; P<0.001; Wilcoxon rank-sum test), and increased the time to first DE requiring intervention (median: 173 vs. 38 days; P<0.001; stratified log-rank test). Differences in quality of life scores were not significant between groups. The adverse event profile was similar for both treatment approaches. Twice-weekly proactive application of 0.03% tacrolimus ointment over 12 months was effective for most paediatric study patients in preventing, delaying and reducing the occurrence of AD exacerbations.

Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes. 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.

Topical application of isotretinoin and adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. To compare the efficacy and tolerability of adapalene gel 0.1% and isotretinoin gel 0.05% in the treatment of acne vulgaris of the face, in a randomized open-label clinical trial. Eighty patients were enrolled and were instructed to apply adapalene gel 0.1% or isotretinoin gel 0.05% once daily over a 12-week treatment period. Efficacy determination included noninflammatory and inflammatory lesion counts by the investigator and global evaluation of improvement. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus. Adapalene and isotretinoin gels were highly effective in treating facial acne. Adapalene gel produced greater reductions in noninflammatory and inflammatory lesion counts than did isotretinoin gel, but differences between treatments were not statistically significant. Adapalene gel was significantly better tolerated than isotretinoin gel during the whole treatment period. The two gels studied demonstrated comparable efficacy. When adapalene and isotretinoin were compared, significantly lower skin irritation was noted with adapalene, indicating that adapalene may begin a new era of treatment with low-irritant retinoids.

The aim of this study was to compare the efficacy and safety of once-daily with twice-daily application of a 0.05% cream formulation of fluticasone propionate in the treatment of atopic eczema in adults and children. Two hundred and seventy patients with moderate to severe atopic eczema were enrolled in the study, and randomized to receive either once-daily or twice-daily fluticasone propionate 0.05% cream for 4 weeks. Patients randomized to the once-daily group also received the vehicle cream to ensure that the study remained blinded. The clinical response of a preselected target area of affected skin was assessed by investigators at weekly intervals and compared with the baseline. Analysis of the investigators' overall assessment of the response of the target area for both the 'intent-to-treat' population and the per protocol population showed that 79-85% of patients were judged a clinical success. For both populations, there was no statistically significant difference between the response to once-daily and twice-daily active treatment (intent-to-treat; P = 0.35; 95% confidence interval for difference -14.2 to +5.0 percentage points: per protocol; P = 0.42; 95% confidence interval for difference -14.7 to +6.2 percentage points.) The improvement in the signs and symptoms was judged a success in 95-97% of patients. There was an equal reduction in severity scores for disease activity in both groups, and the speed of symptom relief was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Three hundred and fifty-four patients with symmetrical dermatoses took part in a multicentre, double-blind, half-side study in order to compare the efficacy of a new topical steroid, diflucortolone valerate 0.3% (Nerisone Forte) against that of an established, potent topical steroid, clobetasol propionate 0.05% (Dermovate). The assessment of overall response, as judged by the physicians preference for one side or another, showed no difference between the two compounds. However, when the results were examined by separate diagnostic category the number of preferences was greater for diflucortolone valerate 0.3% in eczema, and for clobetasol propionate 0.05% in psoriasis, although neither of these differences reached levels of statistical significance. The graded assessments of response indicated that both compounds were highly effective, potent, topical steroids. Eighty-one percent of patients showed marked improvement or heating with diflucortolone valerate 0.3% and 84% showed marked improvement or healing with clobetasol propionate 0.05%. This difference was not statistically significant. Analysis of response, either by diagnosis or grade of severity, showed no statistically significant differences between the two compounds. No significant differences in the incidence of severity of side-effects were observed. It was concluded that the two compounds were of equal clinical efficacy.

Both clobetasol propionate 0·05% (CP 0·05%) and tacrolimus 0·1% (T 0·1%) ointments have been shown to be efficacious and safe in treating vitiligo in the paediatric population. To assess efficacy and safety of these two therapies compared with each other and with placebo. In this prospective study, children aged 2-16 years with vitiligo, stratified into 'facial' (n = 55) and 'nonfacial' (n = 45) groups, were randomized into three arms: CP 0·05% ointment (n = 30), T 0·1% ointment (n = 31) and placebo (n = 29) for 6 months. Successful repigmentation, defined as > 50% improvement, was evaluated by comparing photographs taken at baseline and at 2, 4 and 6 months. In the facial group, 58% of the CP 0·05% group responded successfully compared with 58% of the T 0·1% group, and in the nonfacial group, 39% of the CP 0·05% group responded compared with 23% of the T 0·1% group (P > 0·05). There was a significant difference in response between the CP 0·05% group vs. placebo (P < 0·0001) and the T 0·1% group vs. placebo (P = 0·0004). Spontaneous repigmentation was evaluated as 2·4%. No significant clinical adverse events were noted in any group. Both CP 0·05% and T 0·1% ointments offer similar benefit in paediatric vitiligo, both facial and nonfacial. The facial lesions responded faster than the nonfacial ones.

Delayed pressure urticaria (DPU) is characterized by the appearance of typical painful skin lesions (weals) after pressure stimulus. Oral corticosteroids are effective treatments but long-term therapy is problematic. A new topical formulation of clobetasol propionate 0.05% in thermophobic foam (CF) (Olux) has recently become available. The foam is easy to apply, with low skin residues. To evaluate in a double-blind placebo-controlled trial the efficacy, tolerability and safety of CF in the topical treatment of DPU. Twenty-six subjects with a positive history of DPU (13 men, mean age 44 years) were enrolled in a 4-week trial. CF or the corresponding placebo were applied twice daily. Drug application was performed in the most affected areas and in a target area where a standardized pressure challenge test was performed at baseline and at week 4. Efficacy was evaluated by scoring skin lesions regarding erythema, oedema and itching (0, no sign; 4, severe signs) and by calculating the area of the pressure challenge-induced lesion. Safety was evaluated by measuring plasma levels of adrenocorticotropic hormone (ACTH) and cortisol. CF significantly (P = 0.0001) reduced lesion area by 84% in comparison with baseline values and by 97% in comparison with the placebo group values. Lesion area in the CF group was reduced from 144 cm(2) to 21 cm(2) at the end of the study. No significant differences in lesion area and clinical lesion scores were observed in the placebo group (lesion area 201 cm(2) at baseline; 216 cm(2) after 4 weeks). A significant clinical improvement was observed in all treated skin areas in the CF group. Mean +/- SD erythema score was reduced by CF from 1.8 +/- 0.6 at baseline to 0.6 +/- 0.5 at the end of the treatment (P = 0.001). Similar modifications were observed also for oedema (from 1.6 +/- 0.6 to 0.2 +/- 0.5) and itching score. Nonsignificant modifications of plasma levels of ACTH, cortisol and glucose were observed in both study groups, in comparison with baseline values. No adverse events were recorded during the trial in either treatment group. CF is effective, safe, convenient and well tolerated in the short-term treatment of DPU.

The clinical and histological response to 12 weeks of treatment with a very potent topical fluorinated steroid was studied in 15 patients with vulval lichen sclerosus (LS) who were treated with twice daily applications of clobetasol propionate 0.05% cream (Dermovate, Glaxo U.K.). Thirteen patients completed the study and all showed a marked clinical improvement. Histological measurements of skin biopsies taken before and after treatment showed a significant reduction in the characteristic features of LS. One patient developed contact sensitivity to clobetasol propionate. There was no evidence of infection or skin atrophy during the study. Patients completing the study have been followed up for up to 22 months and have been maintained in remission with moderately potent topical steroids which had previously been ineffective.

As a topical immunosuppressant, tacrolimus ointment may be beneficial in the treatment of seborrhoeic dermatitis, while avoiding adverse effects related to long-term use of topical corticosteroids. To determine the safety and efficacy of topical tacrolimus 0.1% ointment in the treatment of seborrhoeic dermatitis. Sixteen subjects (15 men and one woman) were enrolled in a 6-week, open-label, uncontrolled trial of daily topical tacrolimus 0.1% ointment. Following a 2-week washout period for subjects using conventional therapy for seborrhoeic dermatitis, study medication was applied nightly to affected areas until clinical clearance occurred, and then for 7 days thereafter. Lesional extent and severity were assessed at baseline (day 0), at week 2 and at week 6 using the following parameters: (i). clinical assessment of erythema and scaling using a 0-3 scale; (ii). investigator global assessment; (iii). subject global assessment using a 0-6 scale; and (iv). serial photography. Thirteen of 16 (81%) subjects completed the study protocol; three subjects were lost to follow-up at week 6. Relative to the mean baseline value, the mean lesional erythema scores improved by 66.1% and 70.9% at weeks 2 and 6, respectively. Compared with baseline, the mean scaling scores improved by 63.7% at week 2 and 87.8% at week 6. These observations were statistically significant (P < 0.05, Wilcoxon two-sample test). Mean investigator global assessment scores improved by 76.6% at week 2 and 82.7% at week 6, relative to the mean baseline value. Mean subject global assessment scores also improved, by 69.4% at week 2 and 83.5% at week 6, relative to the mean baseline value. Other than transient application site pruritus/burning in two subjects, no serious adverse events were observed. This pilot study suggests that topical tacrolimus 0.1% ointment is efficacious in the short-term treatment of seborrhoeic dermatitis. Further controlled trials are warranted, to determine its efficacy and safety for this common condition.

For the treatment of a chronic disease like atopic dermatitis, sustained tolerability and efficacy of the applied medication are essential. The present open-label, noncomparative study was conducted to obtain information on the long-term safety and efficacy of 0.1% tacrolimus ointment. Patients aged 2 years or older with an affected body surface area of more than 5%, who previously participated in a clinical trial on tacrolimus ointment, were eligible for this study. The treatment area was defined by the investigator at study entry. Both children and adults applied continuously or intermittently 0.1% tacrolimus ointment twice daily during episodes of active disease plus an additional week after remission over a follow-up period of up to 4 years. The intent-to-treat population comprised 782 patients, with a median age of 22 years (range 2-72). Patients remained in the study for up to 4 years. Approximately half of the patients discontinued the study prematurely; the median follow-up was 1422 days. Median tacrolimus ointment use was 31.2 g during the first week; ointment use decreased during the first year and then remained stable for the remainder of the study. The median cumulative tacrolimus use was 271.5 g at month 6, 462.5 g at month 12, 739.9 g at month 24, 1029.3 g at month 36 and 1320.8 g at month 48. Altogether 51.8% of patients discontinued the study prematurely; the main reasons were withdrawal of consent (13.3%), loss to follow-up (11.3%) and lack of efficacy (9.4%). Adverse events led to study discontinuation in 3.7% of the patients. The most frequent application site events were skin burning and pruritus. These events were most often reported in adult patients during the initial treatment period; prevalence decreased after the first week and remained at a low level throughout the study. Nonapplication site events occurred with stable incidences throughout the study period. In general, calculated daily hazard rates did not indicate an increased risk of adverse events with prolonged treatment. The total affected body surface area decreased substantially upon onset of treatment and efficacy of treatment was maintained until the end of the study with smaller but continuous improvements throughout the follow-up period. Overall, 75% of the patients and 76% of the investigators rated their satisfaction with the treatment as excellent, very good or good at the end of the study or at the time of premature discontinuation. The safety profile of intermittent or continuous long-term application of 0.1% tacrolimus ointment for up to 4 years was consistent with that which has been established from shorter studies and gave no reason for concern. In addition, 0.1% tacrolimus ointment demonstrated sustained efficacy as reflected by the expression of high satisfaction with treatment by both patients and investigators.

Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects. In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD. Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3. By month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6% vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the corticosteroid group; P < 0.001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group. Long-term treatment with 0.1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.

Perianal eczema is an inflammatory skin disease with a high prevalence in most industrialized countries. As general practitioners and dermatologists frequently see patients with perianal eczema the need for efficient, fast and safe therapies is high. Topical calcineurin inhibitors such as tacrolimus (FK506) ameliorate cutaneous inflammation and associated pruritus in an array of inflammatory dermatoses. To investigate the effect of topical tacrolimus in perianal eczema. Twenty-four patients with perianal eczema were treated with tacrolimus 0.1% ointment twice daily on the affected skin area for 2 weeks. All returning patients showed clinical improvement as assessed by macroscopic appearance and clinical score (modified SCORAD index). In this short-term trial we demonstrate that topical tacrolimus 0.1% is safe, efficient and well tolerated in patients with perianal eczema irrespective of the underlying cause.

Nineteen patients with symmetrically distributed patches of vitiligo took part in a double blind trial comparing 0.1% betamethasone valerate in 50% isopropyl alcohol with the unmedicated base. Fifteen patients responded to the medicated application, none to the base alone. Two patients failed to respond and two patients defaulted from the trial.

Pityriasis alba (PA) is a frequent reason for dermatological consultation because of its chronic course, tendency to relapse and aesthetic impact. In view of its strong association with atopic dermatitis, the objective of this open-label study was to assess the efficacy and safety of tacrolimus ointment in the treatment of PA compared with the efficacy of moisturizers. The study population consisted of 60 individuals of phototype III or IV according to Fitzpatrick's classification, aged 6-21 years. Patients were randomly assigned to one of two groups. Subjects in group A were instructed to apply tacrolimus ointment 0.1% twice daily, 12 h apart, on all hypopigmented macules. Standard moisturizers with SPF 20 sunscreen were used on all lesions applied at least 30 min apart from the tacrolimus ointment. Subjects in group B used solely the same moisturizers with sunscreen. Hypopigmented areas were evaluated at baseline and weeks 0, 3, 6 and 9 by investigators for scaling, hypopigmentation and pruritus on a scale of 0-3. Patient satisfaction was also recorded on a scale of 0-3. All adverse effects were recorded. A statistically significant improvement through time, in hypopigmentation, pruritus and scaling was observed in both groups during the course of 9 weeks. Hypopigmentation resolved from a baseline score of 2.38+/-0.64 to 1.15+/-0.54 at week 3, 0.46+/-0.51 at week 6 and 0.00+/-0.00 at week 9 for the group applying tacrolimus ointment 0.1%. The difference in improvement between the two groups was statistically significant on all three assessments for hypopigmentation (P<0.001), and for pruritus on week 6 and 9 assessments (P<0.05). Three patients (11.5%) in the tacrolimus group reported a mild transient sensation of burning. All patients in the tacrolimus group reported they were completely satisfied or just satisfied with the treatment compared with only 50% of patients using the placebo. Tacrolimus ointment 0.1% appears to be an effective and safe treatment for PA.