Influence of pimecrolimus cream 1% on different morphological signs of eczema in infants with atopic dermatitis

BACKGROUND: In the published studies on the efficacy of the topical immunomodulator pimecrolimus, different eczema scores were used, and the impact on morphological key signs of eczema was not analysed. OBJECTIVE: To compare the influence of pimecrolimus cream 1% on different standard eczema scores in infants with atopic dermatitis and to analyse the impact of treatment on the individual morphological key signs of eczema. METHODS: Pimecrolimus cream 1% (n = 129) or double-blind vehicle control (n = 66) was administered for 4 weeks. The Eczema Area and Severity Index (EASI), Investigators' Global Assessment (IGA) and Scoring Atopic Dermatitis Index (SCORAD) were determined and were correlated with each other. RESULTS: Following treatment with pimecrolimus, the EASI, IGA and SCORAD were significantly reduced on day 29 as compared with the vehicle group (p < 0.001, p < 0.001, p = 0.002, respectively). There was a close correlation between EASI, IGA and SCORAD. The single parameters of the EASI were already significantly decreased by day 4 in the pimecrolimus group as compared to vehicle (each p < 0.001). CONCLUSION: Treatment with pimecrolimus 1% cream leads to a rapid improvement of all morphological signs of eczema. The close correlation of different scores was shown for the first time.     

Spotlight on topical pimecrolimus in atopic dermatitis

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.     

Pimecrolimus cream (1%) efficacy in perioral dermatitis – results of a randomized, double-blind, vehicle-controlled study in 40 patients

BACKGROUND: Perioral dermatitis (POD) is a common skin disease and difficult to treat. Pimecrolimus cream (1%) successfully controls atopic eczema. OBJECTIVE: Our aim was to investigate its efficacy in POD. STUDY DESIGN: Single-centre, randomized, double-blind, vehicle-controlled study including 40 POD patients with a 4-week treatment and a 4-week follow-up. Efficacy was assessed by a novel Perioral Dermatitis Severity Index (PODSI) and Finlay's Dermatology Life Quality Index (DLQI). SETTING: Outpatient clinics of a large dermatological hospital in Munich, Germany. RESULTS: During treatment, the PODSI was significantly lower in the pimecrolimus group compared with vehicle (P = 0.005-0.02) whereas at follow-up, no significant differences were observed. At week 2, the responder rates (> or = 50% PODSI improvement) were 50% with pimecrolimus cream (1%) and 25% with vehicle (P = 0.095). DLQI was improved in pimecrolimus group compared with vehicle. CONCLUSION: Results suggest that pimecrolimus cream (1%) effectively treats acute-stage POD.     

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.     

Use of pimecrolimus cream 1% (Elidel) in the treatment of atopic dermatitis in infants and children: the effects of ethnic origin and baseline disease severity on treatment outcome

BACKGROUND: Pimecrolimus cream 1%, a cell-selective inhibitor of inflammatory cytokines, has been shown to be effective in treating atopic dermatitis (AD). This report examines the effect of ethnic origin and baseline disease severity on treatment outcomes in pediatric patients with AD treated with pimecrolimus cream 1%. METHODS: The analysis included 589 patients aged 3 months to 17 years from three 6-week, randomized, multicenter studies of similar design. Patients were treated with pimecrolimus cream 1% or vehicle twice daily. Efficacy, safety and tolerability in Caucasian and non-Caucasian groups were compared. In addition, the effect of baseline disease severity on treatment outcome was investigated. RESULTS: A total of 321 Caucasian and 268 non-Caucasian patients [Blacks, Asians and others (including Hispanics)] with mild, moderate or severe disease at baseline were included. Baseline characteristics were comparable between the pimecrolimus and vehicle control groups and between Caucasian and non-Caucasian groups. Significantly higher efficacy [measured by Investigators' Global Assessment and Eczema Area and Severity Index (EASI) scores] was achieved in the pimecrolimus-treated group, compared with the vehicle group, irrespective of ethnic origin. Baseline disease severity had no effect on treatment outcome: patients with both mild and moderate AD responded well to pimecrolimus (absolute change from baseline in EASI score -2.60 and -5.48, respectively; both P < 0.001). Pimecrolimus cream 1% was safe and well tolerated in all ethnic groups and at all levels of disease severity. CONCLUSIONS: Ethnic origin and baseline disease severity had no effect on treatment outcome with pimecrolimus cream 1% in patients with AD.     

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.     

The treatment of facial atopic dermatitis in children who are intolerant of, or dependent on, topical corticosteroids: a randomized, controlled clinical trial

Background  Atopic dermatitis (AD) is most prevalent in areas of reduced skin barrier reserve, like face and neck, especially in children. Treatment with topical corticosteroids (TCS) is limited due to heightened risk of treatment-associated side-effects, thus necessitating alternative AD therapies.
Objectives  The primary study objective was to determine the efficacy of pimecrolimus cream 1% in children with mild–moderate facial AD dependent on/intolerant of TCS. Secondary objectives included effects on overall Eczema Area and Severity Index (EASI), head/neck EASI, pruritus severity and time to clearance of facial AD.
Methods  A multicentre, double-blind (DB) study of ≤ 6 weeks, followed by a 6-week, open-label (OL) phase was conducted. Two hundred patients (aged 2–11 years) were randomized 1 : 1 to pimecrolimus cream 1% ( n  =   99) or vehicle ( n  =   101) twice daily until clearance of facial AD or for a maximum of 6 weeks (DB phase). Sixteen patients receiving vehicle were allowed to switch to the OL phase at day 22.
Results  Significantly more pimecrolimus-treated vs. vehicle-treated patients were cleared/almost cleared of facial AD (Investigators' Global Assessment 0/1): 74·5% vs. 51·0%, P  <   0·001 (day 43) [57·1% vs. 36·0%, P  =   0·004 (day 22)]. Median time to clearance was 22·0 vs. 43·0 days (pimecrolimus vs. vehicle, respectively). Statistically significant differences for pimecrolimus vs. vehicle were also seen on head/neck EASI, overall EASI, and head/neck pruritus scores. Adverse events were mainly mild–moderate, occurring with similar frequency in both treatment groups.
Conclusions  In children with facial dermatitis intolerant of/dependent on TCS, pimecrolimus cream 1% effectively controls eczema and pruritus and is well tolerated.     

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.     

An exploratory study to evaluate the efficacy of pimecrolimus cream 1% for the treatment of pityriasis alba

BACKGROUND: Use of topical corticosteroids for the treatment of pityriasis alba is limited by their potential side-effects, such as skin atrophy especially with long-term use on the face. Pimecrolimus cream 1% is a topical calcineurin inhibitor that has anti-inflammatory properties, lacks the cutaneous side-effects associated with steroids, and provide a potential benefit for the treatment of pityriasis alba. METHODS: This 10-patient, prospective, single-arm, open-label, single-center, 12-week, investigator-initiated proof of concept study assessed the efficacy, safety, and patient acceptance of pimecrolimus cream 1% twice daily. In addition to pimecrolimus cream, patients used facial emollient containing SPF 15 sunscreen and mild soap-free cleanser. Efficacy assessments were Investigator Global Assessment (IGA) of disease severity and evaluation of uneven skin color, scaling, eczema, follicular keratosis, and pruritus. All efficacy assessments were reported on a 4-point scale (0 = none to 3 = severe). RESULTS: Of the 10 patients enrolled (aged: 12-35 years), all had intensive sun-exposure, 90% had skin type IV-V, and 80% completed the 12-week treatment. At baseline, mean IGA was 1.20 (mild-moderate), uneven skin color was 2.3 (moderate-severe) and scaling was 1.2 (mild). IGA decreased to 0.25 by week 12, uneven skin color improved by week 3 with near complete resolution by week 12 (mean = 0.38) and scaling resolved at week 3. Pruritus, eczema, and follicular keratosis remained at low levels from baseline throughout the course of the study. Patients consistently reported satisfaction with the treatment ("satisfied" or "very satisfied"). No adverse events were reported. CONCLUSIONS: Pimecrolimus cream 1% may represent an alternative for the treatment of pityriasis alba.     

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).     

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.     

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial

Background  Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance.
Objectives  To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD.
Methods  This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2–49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control].
Results  An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points.
Conclusions  In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.     

Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study

BACKGROUND: Pimecrolimus cream (Elidel, SDZ ASM 981), a non-steroid inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms reduces the need for topical corticosteroids. OBJECTIVE: To investigate the efficacy and safety of pimecrolimus cream 1% in the long-term management of adult AD. METHODS: 192 adults with moderate to severe AD were randomised (1:1) for twice daily (b.i.d.) treatment of early signs or symptoms of AD with either pimecrolimus cream 1% or vehicle cream (control group) to prevent progression to flares. Treatment was given as needed for 24 weeks. In the event of flares, a moderately potent corticosteroid (prednicarbate 0.25% cream) was permitted as rescue medication in both groups. The percentage of days on which a topical corticosteroid was used to treat disease flares was the main outcome measure. RESULTS: Corticosteroid medication was used on 14.2% (95% confidence interval, CI: 8.3-21.1) of the days of the 24-week treatment period in the pimecrolimus group and on 37.2% (95% CI: 30.4-44.0) of the days in the control group (p < 0.001). In total, 44.8% (43/96) of patients in the pimecrolimus group did not experience a flare compared with 18.8% (18/96) of patients in the control group. The median time to first flare was 144 days in the pimecrolimus group and 26 days in the control group (p < 0.001). Pimecrolimus treatment was also associated with improvement in signs and symptoms of AD, pruritus, patients' self-assessment and quality of life. CONCLUSIONS: Pimecrolimus cream 1% b.i.d. is an effective, well-tolerated, long-term treatment for AD in adults, substantially reducing the number of flares compared to a conventional therapy and consequently reducing or eliminating the need for corticosteroid treatment.     

Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme

OBJECTIVE: To validate the Eczema Area and Severity Index (EASI) by assessing its internal consistency, reliability and sensitivity to change and by correlating it to other efficacy parameters. DESIGN: Three short-term and two long-term double-blind, randomized, controlled trials, performed in 138 study centres in Europe, South Africa, Australia, New Zealand, and North and South America. PATIENTS AND METHODS: In total, 1550 paediatric patients with atopic dermatitis were studied. Pimecrolimus cream 1% was used twice daily to treat atopic dermatitis. The three short-term studies were placebo controlled. The two long-term studies evaluated the efficacy and safety of early intervention with pimecrolimus to prevent progression to disease flare requiring topical corticosteroid treatment, compared with reactive treatment with topical corticosteroids to treat flares of atopic dermatitis. MAIN OUTCOME MEASURES: Five parameters were measured: (i) the EASI (range of score 0-72); (ii) Investigators' Global Assessment (IGA), using a six-point (0-5) scale; (iii) patients' assessment, using a four-point (0-3) scale; (iv) severity of pruritus assessment, using a four-point (0-3) scale; and (v) a quality-of-life evaluation. RESULTS: The EASI score varied in parallel and in correlation with the IGA, pruritus and patients' assessment. All correlation coefficients were statistically different from 0 (P < 0.05). The EASI correlated well with each of its components, and all paired comparisons were within agreed limits. The EASI showed good sensitivity to changes in severity. CONCLUSION: In a large, multinational patient population with atopic dermatitis, the EASI showed good validity, reliability and sensitivity to change and correlated well with other measures of severity. It therefore qualifies as a valid method of assessment in clinical studies of atopic dermatitis.     

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.     

Pimecrolimus 1% cream for oral erosive lichen planus: a 6‐week randomized,double‐blind,vehicle‐controlled study with a 6‐week open‐label extension to assess efficacy and safety

Objective To assess the efficacy and safety of topical pimecrolimus 1% cream in the treatment of oral erosive lichen planus. Design A 6‐week randomized, double‐blind, vehicle‐controlled phase followed by a 6‐week open‐label phase. Setting Outpatients of the Department of Dermatology, University of Utah. Patients Twenty‐one patients with oral erosive lichen planus were randomized and treated with either pimecrolimus 1% cream or vehicle cream. Intervention Pimecrolimus 1% cream, or its vehicle, were applied twice daily for 6 weeks to each side of the mouth with a 2 × 2 inch gauze pad folded in half and placed directly on the erosive lesion. Main Outcome Measures Efficacy was based on clinical evaluation of Investigator’s Global Assessment (IGA) of the overall severity of the disease, erythema, measurement of the size of any target erosion in millimetres, and assessment of spontaneous pain. Blood levels of pimecrolimus were monitored in all subjects on day 0 and repeated on day 7. Results Pimecrolimus 1% cream was superior to vehicle cream in reducing mean IGA, pain, and erosion size. For the vehicle group that entered the open‐label phase, pimecrolimus 1% cream improved the mean IGA, pain, erosion size, and erythema. Pimecrolimus levels were detected in nine out of 10 of the pimecrolimus‐treated subjects. These levels were consistently low. The pimecrolimus cream was well‐tolerated. No clinically relevant, drug‐related adverse events were reported. Conclusion Pimecrolimus 1% cream was superior to vehicle in reducing pain, erythema, decreasing erosion size, and improving overall severity of disease when compared with vehicle treatment.     

Use of pimecrolimus cream in disorders other than atopic dermatitis

BACKGROUND: Pimecrolimus is indicated for treatment of atopic dermatitis and has been evaluated in many other disorders. OBJECTIVE: To review the efficacy of pimecrolimus in treatment of disorders other than atopic dermatitis. METHODS: We performed a PubMed search of the English-language literature using the key word "pimecrolimus." We reviewed articles reporting the use of pimecrolimus in disorders other than atopic dermatitis and classified them by the type of study used to evaluate efficacy. RESULTS: Randomized, double-blind studies have shown that pimecrolimus is superior to vehicle in treatment of seborrheic dermatitis, hand dermatitis, and asteatotic eczema but have yielded conflicting results regarding intertriginous psoriasis and vitiligo. Open-label studies involving four or more patients have shown favorable results in many disorders, including contact dermatitis, rosacea, lichen sclerosus, and oral and genital lichen planus. Case reports have shown that topical pimecrolimus may be useful in cutaneous graft-versus-host disease, lichen striatus, cutaneous lichen planus, and many other disorders. CONCLUSIONS: Topical pimecrolimus appears to be an effective treatment for many disorders other than atopic dermatitis, especially seborrheic dermatitis, hand dermatitis, and asteatoic eczema. It may be effective in many other disorders, but its role in these disorders remains to be clarified by additional studies.     

Clinical management of atopic eczema with pimecrolimus cream 1% (Elidel) in paediatric patients

Atopic eczema is predominantly a disease of children and infants, and is often a significant burden for both the sufferer and the family. Pimecrolimus cream 1% (Elidel) is a topical calcineurin inhibitor that has been developed for the treatment of inflammatory skin diseases. When applied twice daily, pimecrolimus has been shown to be effective and well tolerated in paediatric patients with mild to moderate atopic eczema, and appears to be particularly suitable for use on the face, the neck and skin folds. Reduction of pruritus or erythema can be seen within 48 hours of initiating treatment, and when used at the first signs or symptoms of recurrence, pimecrolimus can significantly reduce the incidence of flares and the amount of topical corticosteroid used. Long-term pimecrolimus therapy shows that the initial reduction of disease severity (Eczema Area and Severity Index) is sustained and that most patients have minimal residual disease at 2 years. The most common application-site reaction is a mild to moderate, transient, warm/burning sensation occurring in approximately 10% of patients. Blood concentrations of pimecrolimus following topical administration remain low in all patients. Currently there is no evidence for systemic adverse events, immune suppression or alterations in the vaccine response, after short-term or prolonged treatment. In conclusion, pimecrolimus is an effective treatment option for the short-term treatment and long-term control of atopic eczema in paediatric patients.     

Low systemic exposure after repeated topical application of Pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis

BACKGROUND: Pimecrolimus is a cell-selective inhibitor of inflammatory cytokine release developed specifically for the treatment of inflammatory skin diseases. AIM: The objective of this study was to evaluate blood concentrations and tolerability of pimecrolimus during topical treatment. METHODS: Twelve adult patients with extensive atopic dermatitis were enrolled in an open-label, noncontrolled, pharmacokinetic study. The patients were treated twice daily for 3 weeks with pimecrolimus cream 1% on all lesions. Pimecrolimus blood concentrations were measured at regular time points, and the safety and tolerability were monitored throughout the study. RESULTS: In 78% of the 444 blood samples evaluated, pimecrolimus concentrations remained below the limit of quantitation (0.5 ng/ml). The highest concentration measured was 1.4 ng/ml. There was no indication of drug accumulation. Pimecrolimus was well tolerated locally and systemically. CONCLUSION: The 3-week twice daily treatment with pimecrolimus cream 1% results in consistently low pimecrolimus blood concentrations with no accumulation. Pimecrolimus cream appears suitable for the long-term management of atopic dermatitis.     

外用吡美莫司治疗特应性皮炎的系统评价

【摘要】目的 评价外用吡美莫司治疗特应性皮炎的疗效和安全性。方法 计算机检索Cochrane图书馆（2007年第2期）,Medline（1966～2007）,Embase（1974～ 2007）和中国生物医学文献数据库（CBM, 1978～2007）,收集所有外用吡美莫司与赋形剂或外用糖皮质激素制剂或外用他克莫司制剂的随机对照试验（RCT）,由两名评价人员独立提取资料与评价质量,用RevMan软件统计分析。结果 共纳入16篇RCT,包括4241例患者,均为高质量研究。对IGA治疗成功率的Meta分析结果显示：0. 1%吡美莫司与赋形剂比较,OR合并=2.87 [95% CI(2.21,3.73), P <0.001]。0. 1%吡美莫司与0.1%戊酸倍他米松比较, OR=0.15 [95% CI(0.05,0.47), P <0.001 ]。0. 1%吡美莫司与0. 03%他克莫司比较, OR合并=0.74 [ 95% CI(0.39,1.37) ,P=0.33 ]。所有研究均未发现严重的不良反应。结论 外用吡美莫司治特应性皮炎比赋形剂有效,而不如外用强效糖皮质激素有效。0. 1%吡美莫司与0. 03%他克莫司疗效相同。吡美莫司对湿疹面积和严重程度指数评分、瘙痒程度评分、生活质量相关评分均有明显改善。