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.     

Long-term management of facial atopic eczema with pimecrolimus cream 1% in paediatric patients with mild to moderate disease

Background The aim of this post hoc analysis was to evaluate whether treatment of patients with atopic dermatitis (AD) with pimecrolimus cream 1% can decrease the development of flares necessitating the use of a topical corticosteroid on the face and thus reduce the need for use of topical corticosteroids in this sensitive skin area. Patients and methods In a controlled, double‐blind, multicentre study, 140 patients, aged 2 to 17 years, with facial involvement and mild to moderate disease after treatment of the initial flare with prednicarbate 0.25% cream were randomized to an intermittent treatment with pimecrolimus cream 1% twice daily or vehicle for 24 weeks. If a flare occurred, defined as an exacerbation (unacceptable severity of itching/scratching or onset of oozing) not controlled by study medication, patients were treated with prednicarbate 0.25% cream instead. Results Patients in the vehicle group needed prednicarbate treatment on the face on 20.7% of the days vs. 11.7% of the study days in the pimecrolimus group (P = 0.0024). Fifty per cent of patients in the pimecrolimus group had no flare on the face during the treatment period compared with 37.5% of patients in the vehicle group (P = 0.012). The median time to first flare in pimecrolimus‐treated patients was twice as long as in patients receiving vehicle (138 vs. 68 days, P = 0.01). Three adverse events (one case of skin burning) suspected to be related to use of the study medication were reported for three patients (3.9%) in the pimecrolimus group. Conclusion Long‐term intermittent treatment of facial AD in children and adolescents with pimecrolimus cream 1% does significantly reduce the need for topical corticosteroids.     

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.     

Effectiveness and safety of a prevention‐of‐flare‐progression strategy with pimecrolimus cream 1% in the management of paediatric atopic dermatitis

Objective This study was performed to investigate the efficacy and safety of a prevention‐of‐flare‐progression strategy with pimecrolimus cream 1% in children and adolescents with atopic dermatitis (AD). Methods A 26‐week multi‐centre, randomized, double‐blind, vehicle‐controlled study was conducted in 521 patients aged 2–17 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n = 256) or vehicle cream (n = 265). Twice‐daily treatment with study medication was started at the first signs and/or symptoms of recurring AD. If, despite the application of study medication for at least 3 days, AD worsened (as confirmed by the investigator), treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy end point was the number of days on study without TCS use for a flare. Results The mean number of TCS‐free days was significantly higher (P < 0.0001) in the pimecrolimus cream 1% group (160.2 days) than in the control group (137.7 days). On average, patients on pimecrolimus cream 1% experienced 50% fewer flares requiring TCSs (0.84) than patients on vehicle cream (1.68) (P < 0.0001). Patients on pimecrolimus cream 1% also had fewer unscheduled visits (87) than patients on vehicle cream (246). Conclusions In children and adolescents with a history of mild or moderate AD but free/almost free of signs or symptoms of the disease, early treatment of subsequent AD exacerbations with pimecrolimus cream 1% prevented progression to flares requiring TCS, leading to fewer unscheduled visits and reducing corticosteroid exposure.     

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.     

Low systemic absorption and good tolerability of pimecrolimus, administered as 1% cream (Elidel) in infants with atopic dermatitis--a multicenter, 3-week, open-label study

Pimecrolimus cream 1%, a nonsteroid inhibitor of inflammatory cytokines, offers an alternative to corticosteroids in the treatment of atopic dermatitis. Here we evaluate pimecrolimus blood concentrations and tolerability to pimecrolimus cream 1% in 22 infants below 2 years of age with atopic dermatitis (10-92% body surface area affected at baseline). Efficacy was assessed as a secondary objective. Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood concentrations were low, typically (96% of total 100 concentrations measured) below 2 ng/mL, the majority (71%) remaining below 0.5 ng/mL. The highest concentration observed was 2.26 ng/mL. At steady state, there was no indication of accumulation. Pimecrolimus was well tolerated locally and systemically, with no serious adverse events recorded. Most adverse events recorded (35 in 17/22 patients) were typical of the young pediatric population studied, of mild to moderate severity, and not considered to be study-medication related, with the exception of four local adverse effects limited to the site of cream application. No clinically relevant change was observed in physical examination, vital signs, or laboratory safety parameters. A rapid onset of therapeutic effect was observed within the first four days of treatment. Pimecrolimus cream 1% is well tolerated in infants 3 to 23 months of age treated for 3 weeks, and results in minimal systemic exposure.     

StabiEL: Stabilization of skin condition with Elidel – a patients’ satisfaction observational study addressing the treatment,with pimecrolimus cream,of atopic dermatitis pretreated with topical corticosteroid

Background The objective of this 4‐month multicentre observational study was to evaluate safety and efficacy of intermittent long‐term treatment of patients with atopic dermatitis (AD) with pimecrolimus cream 1% in the daily practice and to compare it with the preceding topical corticosteroid‐based therapy in retrospective. Patients and methods Overall severity of AD and individual symptoms were assessed in 3200 patients by the physician, whereas acceptance of treatment and satisfaction of patients was investigated using a patient questionnaire. Results The percentage of patients clear or almost clear of symptoms increased from 12% to 82%. Seventy‐four per cent of physician rated the treatment better than the preceding therapy, and 21% noted no difference. Seventy‐seven per cent of the patients asserted that long‐term intermittent treatment with pimecrolimus reduces the frequency of flares as opposed to less than 27% for topical corticosteroids. Patients also felt that pimecrolimus results in a higher improvement in quality of life; 84% stated that pimecrolimus stabilized the skin compared with 27% for topical steroids. Conclusion Intermittent treatment of AD patients with pimecrolimus cream 1% is effective and well tolerated, and results in higher patient satisfaction compared with topical corticosteroids in retrospective.     

Pimecrolimus 1% cream in the treatment of vulvar lichen sclerosus in postmenopausal women

Background Vulvar lichen sclerosus (LS), a poorly recognized chronic inflammatory skin disease, may represent a therapeutic challenge. Pimecrolimus cream 1% is a nonsteroidal, selective inflammatory cytokine inhibitor that has recently been indicated for some inflammatory cutaneous diseases. Objective To investigate the efficacy, tolerability, and safety of 1% pimecrolimus cream therapy in postmenopausal women with LS. Methods A total of 16 patients applied pimecrolimus cream 1% twice a day over the first 3 months and then as required. All the patients completed this study and were then followed up over the next 12 months. The symptoms and clinical appearance of the lesions in every subject were recorded before and after treatment using a severity scale. Results Using pimecrolimus, most of the patients exhibited a significant improvement with respect to symptoms and the clinical appearance of the disease. After 3 months of treatment, complete remission was seen in 11 patients, partial remission in four, whereas one patient experienced no response at all. Over the subsequent 12 months of follow‐up, 10 patients exhibited complete remission while five had partial remission. Four cases with complete remission experienced a few relapses during the follow‐up period. Older patients and those with an advanced stage of the disease responded poorly. No significant side effects were observed. Conclusions Pimecrolimus cream 1% appears to be an effective and well‐tolerated therapeutic alternative option in the treatment of early stage of vulvar LS. Pimecrolimus may reduce the incidence of flare ups, improve long‐term disease control, and enhance the patients’ quality of life, especially in postmenopausal women.     

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

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.     

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.     

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.     

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.     

Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. A randomized controlled trial

BACKGROUND: Previous studies suggested that early intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a relapse of atopic dermatitis (AD) following remission may prevent the occurrence of more severe flares and therefore reduce corticosteroid exposure in the long term. However, this possibility was not rigorously evaluated. OBJECTIVES: To evaluate the effectiveness of pimecrolimus cream 1% for the prevention of flare progression in adults with AD. METHODS: A 26-week randomized controlled study was conducted in 543 patients aged>or=18 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n=277) or matching vehicle cream (n=266). Twice-daily treatment with study medication was started at the onset of the first signs and/or symptoms of a relapse. If disease worsened, despite the application of study medication for at least 3 days, treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy endpoint was the number of days without TCS use for disease worsening. RESULTS: The mean number of TCS-free days was significantly higher (P<0.001) in the pimecrolimus cream 1% group (152 days) than in the vehicle cream group (138.7 days). In comparison with vehicle cream, pimecrolimus cream 1% reduced the mean number of flares requiring TCS use from 1.39 to 0.97 (P=0.0014). Patients on pimecrolimus cream 1% made 30% fewer unscheduled visits (156) than patients on vehicle cream (223). CONCLUSIONS: In adults with a history of mild or moderate AD but free of active skin lesions, intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a subsequent recurrence reduces the number of flares requiring TCS use and decreases the number of disease-related office visits.     

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.     

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.     

Effect of pimecrolimus cream 1% on the long-term course of pediatric atopic dermatitis

BACKGROUND: This report investigates the effect of pimecrolimus cream 1% (Elidel, Novartis pharma AG, Basel, Switzerland), a nonsteroid, cell-selective, cytokine inhibitor on the course of atopic dermatitis (AD), as assessed by changes in body surface involvement and pattern of drug use over time. METHODS: Data from 961 patients in two 1-year double-blind, multicenter, pediatric studies of similar design were analyzed: 250 infants (aged 3-23 months) were randomized 4 : 1 and 711 children (aged 2-17 years) were randomized 2 : 1 to receive pimecrolimus cream 1% or vehicle, respectively. Emollients were used by all patients to alleviate dry skin and, at the first signs or symptoms of AD, pimecrolimus or vehicle was applied twice daily to prevent progression to flares. If flares occurred in either group, moderately potent topical corticosteroids were mandated. RESULTS: Pimecrolimus was applied for 68.4% (infants) and 53.8% (children) of study days, and frequency of use of pimecrolimus decreased over time, reflecting improvement in disease control. The mean total body surface area affected decreased continuously over time. Significantly more patients in the pimecrolimus than control groups were maintained without corticosteroid therapy (infants: 63.7% vs. 34.8%, P < 0.001; children: 57.4% vs. 31.6%, P < 0.001, respectively). CONCLUSION: The need for pimecrolimus therapy decreases over time as the patients' disease improves. Hence, once long-term management of AD with pimecrolimus is established, the burden of disease for both the patient and the caregiver decreases significantly and disease-free periods become more frequent.     

Skin physiological parameters confirm the therapeutic efficacy of pimecrolimus cream 1% in patients with mild-to-moderate atopic dermatitis

Abstract:  In this double-blind, within-patient vehicle-controlled study, patients with mild-to-moderate atopic dermatitis (AD) were treated for 3 weeks twice daily with pimecrolimus cream 1% on one forearm and with vehicle cream on the other forearm. Efficacy of treatment was assessed clinically using the Atopic Dermatitis Severity Index (ADSI), the Investigators Global Assessment (IGA) and the pruritus visual analogue scale. In parallel, blood microcirculation in the skin was measured as an objective parameter for skin inflammation. Skin hydration and transepidermal water loss (TEWL) were monitored as parameter relevant for the barrier function. Treatment with pimecrolimus cream 1% resulted in a quick and marked improvement of signs and symptoms of AD and a significant reduction of microcirculation from 33.90 to 15.55 AU ( P  < 0.0001). Skin hydration increased continually from 42.86 to 52.69 AU ( P  = 0.002) and TEWL decreased from 35.30 to 21.50 g/m²/h ( P  = 0.001), indicating restoration of skin barrier. At vehicle-treated sites changes of skin physiological parameters were less pronounced and observed only initially with later plateau or even reversal. At the end of the study, there were significant differences for all measured skin physiological parameters between pimecrolimus cream 1% and vehicle: microcirculation 12.15 AU ( P  = 0.004), skin hydration 7.12 AU ( P  = 0.002), TEWL 11.38 g/m²/h ( P  = 0.004). Non-invasive evaluation of microcirculation and barrier functionality thus represent a valuable tool for the objective assessment of treatment response to pimecrolimus cream 1%.