Pimecrolimus 1% cream versus betamethasone 17-valerate 0.1% cream in the treatment of facial discoid lupus erythematosus: a double-blind, randomized pilot study

Background.  Discoid lupus erythematosus (DLE) is commonly treated with topical agents, the most important of which are glucocorticosteroids. However, prolonged use of these agents, especially on sensitive areas such as the face, may result in side-effects (e.g. atrophy and telangiectases) by altering collagen synthesis. Therefore, alternative treatments are needed for these patients.
Aim.  To investigate and compare the efficacy of topical pimecrolimus 1% cream and topical betamethasone 17-valerate 0.1% cream on facial lesions of DLE.
Methods.  This was a randomized double-blind pilot study, performed in outpatient clinics of two major referral hospitals. Ten patients aged 20–53 years with moderate to severe DLE of the face were randomized into two groups for 8 weeks of treatment and 8 weeks of follow-up after treatment. In this double-blind study, one group applied pimecrolimus 1% cream twice daily and the other group applied betamethasone valerate 0.1% cream twice daily to facial lesions. Efficacy end-points included a combined score based on evaluation of erythema, infiltration and presence of scale.
Results.  Efficacy end-points showed significant improvement in both groups. A decrease of 86% and 73% in clinical severity scores was obtained for pimecrolimus and betamethasone, respectively ( P  = 0.043). There was no significant difference between the two groups in terms of efficacy ( P  = 0.1). No adverse effect was found at the end of the 8-week trial in any of our patients.
Conclusions.  The efficacy of pimecrolimus 1% cream is comparable with that of betamethasone valerate 0.1% cream in treating facial DLE.     

Improvement in pruritus in children with atopic dermatitis using pimecrolimus cream 1%

The objective of this study was to assess time to onset of pruritus improvement in a pediatric population treated with pimecrolimus cream 1%. This 8-day, double-blinded, vehicle-controlled study randomized 174 children and adolescents (aged 2-17 years) with mild to moderate atopic dermatitis (AD) and moderate to severe pruritus to twice-daily applications of pimecrolimus cream 1% or vehicle. There were no significant between-group differences in demographics or baseline disease characteristics. Pruritus was assessed by subjects using a 4-point pruritus severity scale (0-3). The primary efficacy variable was time to a 1 point or more improvement in pruritus score from baseline. The 2 treatment groups were compared using log-rank testing of the time-to-event data. In the per-protocol (PP) population, median times to a 1 point or more improvement in pruritus score were 48 and 72 hours for pimecrolimus and vehicle groups, respectively (P = .038). From day 3 onward, significantly more subjects (P = .023) in the pimecrolimus group versus the vehicle group reported complete pruritus resolution. Pimecrolimus cream 1% improved pruritus within 48 hours in children and adolescents with mild to moderate AD and achieved complete resolution of pruritus in a significantly greater number of subjects in the pimecrolimus group versus the vehicle group by the end of the 7-day treatment period (P = .008).     

Calcipotriol cream with or without concurrent topical corticosteroid in psoriasis: tolerability and efficacy

The objectives of the study were to determine whether concurrent treatment with calcipotriol (50 μg/g) and either clobetasone 17-butyrate cream (0.5 mg/g) (moderate potency) or betamethasone 17-valerate cream (1 mg/g) (potent) or placebo (vehicle of calcipotriol) was more effective and/or caused less skin irritation than calcipotriol cream (50 μg/g) used twice daily. It was a multicentre, double-blind, parallel group study. Patients applied calcipotriol cream in the morning and either vehicle (n = 174), calcipotriol (n = 174), clobetasone (n = 175) or betamethasone creams (n = 176) in the evening for up to 8 weeks. Adverse events led to withdrawal in 20 patients (2.9%). The mean percentage change in PASI (psoriasis area and severity index) was ?40.6 in the calcipotriol/vehicle group, ?48.3 in the calcipotriol/calcipotriol group, ?53.7 in the calcipotriol/clobetasone 17-butyrate group and ?57.5 in the calcipotriol/betamethasone 17-valerate group. A statistically significant difference was seen between the four treatment groups (P = 0.006) with calcipotriol/vehicle being less effective than the other treatments. A statistically significant difference in favour of calcipotriol/betamethasone 17-valerate was seen between the calcipotriol/calcipotriol group and the calcipotriol/betamethasone 17-valerate group. The majority of adverse events were skin irritations, which were reported for 31.2% of patients treated with calcipotriol/vehicle, 34.3% of patients treated with calcipotriol twice daily and 23.8% vs. 17.1% of patients treated with calcipotriol/clobetasone 17-butyrate and calcipotriol/betamethasone 17-valerate, respectively. Skin irritation was seen statistically significantly less frequently in patients treated with calcipotriol/ clobetasone 17-butyrate or calcipotriol/betamethasone 17-valerate (P = 0.001), whereas no difference was seen between the other groups. In conclusion, calcipotriol applied twice daily was as effective as calcipotriol/clobetasone 17-butyrate, but slightly less effective than calcipotriol/betamethasone 17-valerate. The incidence of skin irritation was less for patients using concurrent corticosteroids, whereas treatment with calcipotriol/vehicle did not reduce the incidence of skin irritation when compared with calcipotriol twice daily.     

Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents

BACKGROUND: The ascomycin derivative pimecrolimus (ASM 981) is a cell-selective cytokine inhibitor, specifically developed for the treatment of inflammatory skin diseases. OBJECTIVE: When applied topically, pimecrolimus cream 1% has shown promise as a treatment for inflammatory skin conditions, including atopic dermatitis (AD) in children and adults, allergic contact dermatitis, and chronic contact irritant hand dermatitis in adults. METHODS: In two independent 6-week, randomized, multicenter studies of identical design, the efficacy and safety of pimecrolimus cream 1% in children with predominantly moderate AD were compared with vehicle. Pooled data from a total of 403 patients were used in the analysis. The primary efficacy parameter was the Investigator's Global Assessment (IGA) score. Secondary parameters included Eczema Area and Severity Index (EASI) and severity of pruritus scores. Subjects were also asked to assess their disease control as uncontrolled, limited, good, or complete. RESULTS: Significant therapeutic benefits relative to vehicle were observed in the pimecrolimus-treated group at the first efficacy assessment, 8 days after initial application of the study medication (eg, relief of pruritus). At each subsequent postbaseline visit, pimecrolimus-treated patients showed significant improvement relative to controls in all efficacy measures. The medication was well tolerated. CONCLUSION: Pimecrolimus cream 1% appears to be a safe and effective alternative to currently used therapies for AD.     

Randomized, placebo-controlled, double-blind study on clinical efficacy of ciclopiroxolamine 1% cream in facial seborrhoeic dermatitis

BACKGROUND: Antifungal agents are beneficial in the treatment of seborrhoeic dermatitis. OBJECTIVES: To perform a randomized, vehicle-controlled, double-blind clinical study with an antifungal ciclopiroxolamine (CIC) 1% cream in patients with mild-to-moderate seborrhoeic dermatitis of the face. METHODS: One hundred and twenty-nine patients were enrolled, 57 patients in the CIC group and 72 patients in the vehicle group, and comprised the study population for efficacy (intent-to-treat analysis) and safety. Patients were randomly allocated to apply either the CIC cream or the vehicle on their facial lesions, twice daily for a maximum of 28 days (initial phase), followed by a once daily application of the test products for another 28 days (maintenance phase). Test lesions were defined as lesions localized in the nasolabial folds and/or the eyebrow. The main efficacy parameter (end-point) was the proportion of patients who achieved complete disappearance of erythema and scaling (treatment responders) at the end of the initial phase (28 days or less) and of the maintenance phase (28 days). RESULTS: At baseline, both treatment groups were comparable in terms of demographic data and lesional status. At the end of the initial phase, responders to treatment were higher with CIC (25 patients, 44%) than with the vehicle (11 patients, 15%) (P < 0.001, Fisher exact test). At the end of the maintenance phase, responders in both groups were even higher, comprising 27 patients (63%, n = 43) in the CIC group and 15 patients (34%, n = 44) in the vehicle group (P < 0.007, intergroup analysis). The local tolerance was good in the two groups, except for a higher rate of lesional exacerbation in the vehicle group. No drug-related systemic adverse event was observed during the study. CONCLUSIONS: CIC administered in a cream demonstrated a good therapeutic value in mild-to-moderate seborrhoeic dermatitis of the face.     

Occlusive treatment of chronic hand dermatitis with pimecrolimus cream 1% results in low systemic exposure,is well tolerated,safe, and effective. An open study

BACKGROUND: Pimecrolimus cream 1% (Elidel, SDZ ASM 981) is a novel, non-steroid inflammatory cytokine inhibitor, effective in the treatment of atopic dermatitis. Here, we evaluate the treatment of chronic hand dermatitis with pimecrolimus cream 1%. OBJECTIVES: To determine pimecrolimus blood concentrations, and evaluate the safety, tolerability and efficacy following application of pimecrolimus cream 1% to subjects with chronic hand dermatitis. METHOD: In this open-label, multiple-topical-dose, non-controlled, pharmacokinetic study, pimecrolimus cream 1% was applied twice daily to dorsal and palmar areas (affected and unaffected) of both hands. Evening applications (except day 8) were immediately followed by overnight occlusion (> or =6 h). Full pharmacokinetic profile (days 1, 8 and 22), trough concentrations (days 3 and 15), physical examinations, laboratory measurements and adverse events were recorded. Efficacy was assessed via Investigators' Global Assessment (IGA), total key signs and symptoms and the subject's overall self-assessment. RESULTS: Twelve patients completed the study. The majority of pimecrolimus blood concentrations (73.6%) remained below the limit of quantitation (0.1 ng/ml). The maximum concentration observed was 0.91 ng/ml and the maximum area under the concentration-time curve from 0-12 h post dose was 7.6 ng.h/ml. Treatment was well tolerated locally and systemically. No serious adverse events occurred; 4/13 subjects showed a total of 6 adverse events at the application site: burning (n=4), and pruritus (n=2). No clinically relevant or drug-related changes were observed. Clear efficacy of the treatment was shown by all 3 assessment methods. Disease state at day 22 had improved in 11 (85%) subjects compared with baseline (IGA). CONCLUSION: Twice daily topical treatment of moderate to severe chronic hand dermatitis with pimecrolimus cream 1% results in low pimecrolimus blood levels, is well tolerated, safe, and effective.     

A randomized controlled trial of pimecrolimus cream 1% in adolescents and adults with head and neck atopic dermatitis and intolerant of, or dependent on, topical corticosteroids

BACKGROUND: There is a need for alternative treatments for atopic dermatitis (AD) of the face and neck as long-term use of topical corticosteroids (TCS) is associated with skin atrophy and telangiectasia and some patients develop allergy, intolerance or other side-effects. OBJECTIVES: This study was designed to assess the efficacy and safety of pimecrolimus cream 1% in patients with AD of the face and neck who are either dependent on, or intolerant of, TCS. METHODS: A 12-week study comprising a 6-week, double-blind, randomized, vehicle-controlled phase was conducted, followed by a 6-week, open-label phase. Two hundred patients aged 12 years or over with mild to moderate head and neck AD, intolerant of, or dependent on, TCS were randomized to either pimecrolimus cream or vehicle cream. The primary efficacy criterion was the facial investigator's global assessment score at 6 weeks. Secondary efficacy criteria were head and neck Eczema Area and Severity Index (EASI), pruritus score and eyelid dermatitis. Facial skin atrophy and telangiectasia were assessed with dermatoscopy. RESULTS: A significantly higher percentage of patients treated with pimecrolimus was cleared or almost cleared of facial AD compared with vehicle (47% vs. 16%, respectively). A statistically significant difference was also seen on head and neck EASI and pruritus score. Significantly more pimecrolimus-treated patients than vehicle-treated patients achieved clearance of eyelid dermatitis (45% vs. 19%, respectively). Among the 77 patients with skin atrophy at baseline, treatment with pimecrolimus was associated with a reversal in skin thinning. Of the 112 patients with telangiectasia at baseline, no statistically significant difference was seen between treatment groups. Adverse events occurred with similar frequency in both groups. CONCLUSION: Pimecrolimus cream 1% is effective in patients with head and neck dermatitis intolerant of, or dependent on, TCS. Reversion of skin atrophy may occur during TCS-free intervals.     

Twice-daily versus Once-daily Applications of Pimecrolimus Cream 1% for the Prevention of Disease Relapse in Pediatric Patients with Atopic Dermatitis

Abstract:  The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score ≥ 3 and pruritus score ≥ 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily ( n  = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31–1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.     

Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study

The efficacy, safety and tolerability of calcipotriol cream was compared with betamethasone 17-valerate cream in the treatment of plaque-type psoriasis in a multicentre double-blind, parallel group study. Patients with stable mild-to-moderate chronic disease were randomized to treatment with either calcipotriol, 50 μg/g, in a cream formulation (210 patients) or betamethasone 17-valerate cream, 1 mg/g (211 patients). After a wash-out period of 2 weeks. the treatment was applied twice daily, without occlusion. for 8 weeks or to complete clearing. The severity of psoriasis was assessed using the PASI at baseline and after 4 and 8 weeks treatment. The mean percentage reduction of PASI from baseline to end of treatment was 47.8% in the calcipotriol group and 45.4% in the betamethasone group. The reduction from baseline was highly significant in both groups. but the differecnce between the groups was not significant. There was a difference in the reduction in thickness of the lesions in favour of calcipotriol. The investigator's as well as the patient's overall assessment of treatment response at end of treatment showed no difference between the two treatment groups. Treatment-related adverse events were more frequent with calcipotriol thanbetamethasone. Lesional/perilesional irritation was reported in 16% and 9% (P=0.03). and facial irritation in 10% and 0.5% (P<0.001), respectively. No change was found in serum levels of calcium. Calcipotriol in a cream formulation was effective, safe well-tolerated. and equal in effect to betamethasone valerate cream.     

Comparative study of ketoconazole 2% foaming gel and betamethasone dipropionate 0.05% lotion in the treatment of seborrhoeic dermatitis in adults.

Sixty-two patients with seborrhoeic dermatitis were treated topically with a 2% ketoconazole foaming gel or with a 0.05% betamethasone dipropionate lotion in a single-blind study for 4 months. Changes in the number of Pityrosporum ovale were scored by a mycologist. The investigator rated the severity of erythema, scaling and itching of the patients' scalp, eyelashes, nasolabial folds and thorax. In addition, both the investigator and the patients evaluated the treatments globally. At the end of treatment, the response rate for ketoconazole 2% foaming gel was significantly higher than that for betamethasone dipropionate 0.05% lotion according to the global evaluation by the physician (89 vs. 62%, p less than 0.05) and the patient (89 vs. 65%, p less than 0.05). Ketoconazole was also superior to betamethasone with reference to the evolution of the symptoms, irrespective of their localization. This efficacy manifested itself by a significant reduction of the number of P. ovale on the scalp in the ketoconazole group (p less than 0.001) compared to the betamethasone group, in which the count was hardly changed during therapy. The treatment was also better tolerated in the ketoconazole group (5 vs. 16 patients with side-effects, p less than 0.001). It is concluded that ketoconazole 2% foaming gel offers an excellent alternative to local corticosteroids in the treatment of seborrhoeic dermatitis.     

Treatment with pimecrolimus cream 1% clears irritant dermatitis of the periocular region, face and neck

Background  Irritant dermatitis of the face and neck is particularly prevalent in women ≥ 30 years old, who typically present with periocular cutaneous symptoms. Current therapies are limited, indicating a need for rapid, effective alternatives. Pimecrolimus cream 1%, a nonsteroid, cell-selective inhibitor of inflammatory-cytokine release, is effective in the treatment of inflammatory skin diseases, such as chronic irritant dermatitis of the hands, and thus offers a potential therapeutic option for this indication. This study reports on the safety and efficacy of pimecrolimus treatment in patients with irritant periocular dermatitis, extending to the face and neck in some patients.
Methods  Twenty-seven patients with periocular irritant dermatitis (extending onto the face and neck in eight) were treated twice daily with pimecrolimus cream 1% for 7 d, followed by once-daily application for a further 7 d. Erythema, swelling, and pruritus were assessed at baseline, weeks 1–4 using a 4-point clinical score (0, absent; 1, mild; 2, moderate; and 3, severe).
Results  All patients showed marked improvement within 2–3 d of treatment with disease clearance in 23 of 27 patients within 14 d. In the remaining four patients, mild relapse occurred at weeks 3–4, but improvement was observed following a further 10-d treatment. Side-effects were mild and transient.
Conclusion  Pimecrolimus cream 1% provides a new potential option for treatment of irritant dermatitis of the periocular region, head and neck. Further double-blind, controlled studies are required to confirm the efficacy and safety of pimecrolimus cream 1% for this indication.     

Pimecrolimus cream 1% for papulopustular rosacea: a randomized vehicle-controlled double-blind trial

BACKGROUND: Rosacea remains difficult to treat, despite many therapeutic options. OBJECTIVES: To investigate the effect of pimecrolimus cream 1% (Elidel; Novartis Pharma, Nuremberg, Germany) in the treatment of papulopustular rosacea. METHODS: Forty patients with rosacea (25 men and 15 women, mean age 58 years) were enrolled in a randomized, vehicle-controlled, double-blind study. For 4-8 weeks, patients applied pimecrolimus cream or vehicle twice daily to the involved areas on the face. Rosacea severity score, subjective severity assessment and quality of life assessment were obtained, along with photographic documentation. RESULTS: Both treatment groups of 20 patients showed an improvement after 4 weeks. The differences were not significant (P > 0 x 05) with regard to mean absolute values, mean percentage changes from baseline, or mean absolute values as differences from baseline for the total score or scores of the different clinical signs (erythema, papulation, scaling and pustules). In the subjective severity score and the quality of life assessment, there was also no significant difference between pimecrolimus and the vehicle (P > 0 x 05). CONCLUSIONS: Treatment of rosacea for 4-8 weeks with the topical calcineurin inhibitor pimecrolimus cream 1% was not more efficacious than treatment with the vehicle cream.     

Efficacy of pimecrolimus 1% cream in the long term management of atopic hand dermatitis. A double-blind RCT

Background: Efficacy and steroid sparing effects of pimecrolimus 1 % cream in atopic dermatitis have been shown recently, but there is no data on efficacy in long term management of atopic hand dermatitis. This study aims to investigate the efficacy of pimecrolimus 1 % cream as maintenance therapy in patients suffering from atopic hand dermatitis. Patients and Methods: A double‐blind vehicle controlled study in 40 adult patients with atopic hand dermatitis (IGA < 3) comparing the efficacy of twice daily application of pimecrolimus 1 % cream given as maintenance treatment versus vehicle over a 8 week period after clinical response (IGA < 2) to a 1–3 week pre‐treatment with mometasone fuorate 0.1 % was performed. Primary endpoint was the time to relapse (IGA > 3). Results: Thirty‐six out of 40 patients were randomised to receive either pimecrolimus 1 % (P) or vehicle cream (V). The number of patients with stable remission in patients randomised to pimecrolimus (53.8 %) and vehicle (43.8 %) did not achieve statistical significance between the groups (p = 0.41). Subgroup analysis of patients with initially moderate dermatitis (IGA = 3, n = 20) showed a trend towards a better outcome for the pimecrolimus group (stable remission P = 81.8 % versus V = 55.6 %) (p = 0.244). Conclusions: Pimecrolimus 1 % cream twice daily was not superior to vehicle in the sequential maintenance therapy of atopic hand dermatitis, but efficacy in moderate forms should be investigated in further studies.     

Pimecrolimus cream 1%: a potential new treatment for chronic hand dermatitis

A multicenter, randomized, vehicle-controlled, 3-week study was conducted in patients with chronic hand dermatitis (HD) of various etiologies and locations to identify subgroups particularly responsive to twice-daily application of pimecrolimus cream 1% with overnight occlusion. A total of 294 patients were randomized to the study. By the final visit on day 22, there was a trend toward greater clearance in patients who received pimecrolimus than in those treated with vehicle cream. An analysis of treatment success by various stratification factors was performed, and it was found that palmar involvement had notable impact on response (P = .033). Patients in the pimecrolimus group continued to improve throughout the study; however, in the vehicle group, improvement plateaued after 15 days. Pimecrolimus was well tolerated, with a low rate of application-site reactions such as burning. Pimecrolimus cream 1%, when used twice daily with overnight occlusion, may be of benefit in the management of chronic HD.     

Blood concentrations, tolerability and efficacy of pimecrolimus cream 1% in Japanese infants and children with atopic dermatitis

Pimecrolimus cream 1% is a topical calcineurin inhibitor for the treatment of atopic dermatitis. Minimal systemic exposure to pimecrolimus has been previously observed in Caucasian pediatric patients treated with the cream twice daily for up to 1 year. The objective of this open-label, non-comparative, multicenter study was to assess the systemic exposure, tolerability and efficacy of pimecrolimus cream 1% when used twice daily for 3 weeks in pediatric patients of Japanese background. The patient cohort consisted of 17 Japanese infants and children (age range, 3.6 months to 11.6 years) with atopic dermatitis of at least mild severity affecting >or=10% of the total body surface area (range, 10-48%). Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood levels of pimecrolimus were determined on days 1, 10 and 22. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, physical condition and vital signs. Efficacy parameters included the Eczema Area and Severity Index, the Investigators' Global Assessment and the pruritus score. The median exposure to pimecrolimus cream 1% was 22 treatment days (range, 9-29 treatment days). Pimecrolimus blood concentrations were <0.5 ng/mL in 94% of samples on day 1, in 93% of samples on day 10 and in 100% of samples on day 22, with no indication of an increase with increasing body surface area treated (up to 48% of the total body surface area). No drug-related systemic adverse events or serious adverse events were reported. Treatment was effective according to all efficacy parameters. The findings of this study indicate that the use of pimecrolimus cream 1% results in minimal systemic absorption of the active ingredient in pediatric patients of Japanese background with extensive disease.     

Safety and efficacy of pimecrolimus cream 1% in the daily practice: Results of a patient self‐observation study in patients with atopic dermatitis

Background: Pimecrolimus cream 1% has proven to be well‐tolerated and effective in controlled clinical studies in patients with atopic dermatitis (AD). In a 15‐week patient self‐observation study, safety and efficacy was investigated in the daily practice. Patients and methods: 3502 patients with AD (mean age 26.2 ± 18 years, 62% female) received pimecrolimus cream 1% from 810 physicians in the German Federal Republic.The severity of the disease was assessed at baseline, two times during the 15‐week observation period and at the end of treatment.Patients recorded daily the degree of erythema and pruritus. At the end of treatment, safety and efficacy were assessed by the physician based on patient's daily records and by the patient. Results: The percentage of patients with severe or massive AD decreased from 25% to 7%, whereas the percentage of patients without or with mild symptoms increased from 9% to 55%.The efficacy of treatment was rated by physicians as good or very good in 83.5% of cases and by 79% of patients.At baseline 35% of the patients were free of flares as compared to 75% at the end of therapy. Disease control was better in patients who followed the recommended treatment algorithm for pimecrolimus cream.Tolerability was mostly rated as good or very good. Conclusion: Treatment with pimecrolimus cream 1% for patients with AD is well‐tolerated and effective in daily practice.     

Inhibition of T-cell activation in vitro in human peripheral blood mononuclear cells by pimecrolimus and glucocorticosteroids and combinations thereof

Pimecrolimus is an ascomycin macrolactam derivative that has been recently approved for the topical treatment of atopic dermatitis. In this study we report for the first time on a direct comparison of the inhibitory activity of pimecrolimus and the glucocorticosteroids betamethasone 17-valerate, dexamethasone and hydrocortisone at the level of T-cell proliferation and cytokine production. Stimulated human peripheral blood mononuclear cell (PBMC) systems were used that are either sensitive or resistant to calcineurin inhibitors or glucocorticosteroids. Pimecrolimus and the glucocorticosteroids inhibited dose-dependently T-cell proliferation and cytokine production in a sensitive system (anti-CD3 mAb-stimulated PBMC) with the following rank order of potency: pimecrolimus approximately betamethasone 17-valerate approximately dexamethasone > hydrocortisone. In resistant systems (anti-CD3 plus anti-CD28- or Staphylococcal enterotoxin B-stimulated PBMC), pimecrolimus or the glucocorticosteroids alone exerted either no effect, or only a partial inhibitory effect. However, combinations of pimecrolimus with a glucocorticosteroid synergistically and strongly inhibited T-cell proliferation. Taken together, the data indicate that medium potency glucocorticosteroids, such as betamethasone 17-valerate and dexamethasone, are as potent T-cell inhibitors as pimecrolimus. Furthermore, the experimental evidence suggests that combinations of glucocorticosteroids and pimecrolimus could be used clinically to achieve superior therapeutic efficacy, when monotherapy with the individual agents is unsatisfactory.     

Pimecrolimus cream 1%: A new development in nonsteroid topical treatment of inflammatory skin diseases

Atopic dermatitis (AD) is one of a family of inflammatory skin diseases (psoriasis, irritant contact dermatitis, and allergic contact dermatitis). Dermal inflammation and production of proinflammatory cytokines by activated T cells is a prominent and defining characteristic in all of these conditions. Corticosteroids, though effective and potent immunosuppressants, are associated with a number of systemic and local adverse effects. The ascomycin derivative pimecrolimus (formerly ASM 981) is a nonsteroid with topical anti-inflammatory activity. Pimecrolimus cream 1% is minimally absorbed into the circulation; thus, it has a low bioavailability-reducing the risk for systemic adverse effects. The efficacy and safety of pimecrolimus cream 1% has been well shown in diverse patient populations with inflammatory skin diseases in several well-controlled trials. Significant and rapid amelioration of the signs and symptoms of AD was established in 3 studies lasting 6 weeks each, evaluating 589 pediatric patients. In a 1-year study, pimecrolimus was applied at the first signs and symptoms of eczema to prevent the progression of AD to flares. Flares were prevented in over 50% of patients who used pimecrolimus cream 1%, reducing or completely eliminating the need for topical corticosteroids during a 1-year treatment period. Results in pimecrolimus studies in chronic irritant hand dermatitis and chronic hand dermatitis of mixed causes indicate potential for use in these important diseases, and further study in these indications is warranted.     

Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis

BACKGROUND: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). OBJECTIVE: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. METHODS: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. RESULTS: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. CONCLUSION: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients' quality of life.     

A double-blind comparison of sulconazole nitrate 1% cream with clotrimazole 1% cream in the treatment of dermatophytoses

Forty patients with dermatophytosis were treated with either sulconazole 1% cream or clotrimazole 1% cream (twenty patients in each group) twice daily for 4 weeks. Overall clinical improvement with respect to baseline at weeks 2, 3 and 4 favoured sulconazole-treated patients (the differences were statistically significant). The weekly mean severity scores for the sulconazole-treated patients for erythema, scaling, fissuring and itching were consistently lower than those for the clotrimazole-treated patients and the differences were statistically significant for erythema and sealing. It was concluded that sulconazole nitrate 1% cream is very effective against various dermatophytoses.