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 in infants with atopic dermatitis in a 1-year pharmacokinetic study with pimecrolimus cream 1%*

Systemic drug exposure following the application of topical agents is a very important safety consideration, particularly in infants, who have a significantly higher ratio of body surface area to body mass than older children and adults. Here, we report on drug exposure in five infants aged 5.7-11.9 months at baseline, with extensive, moderate-to-severe atopic dermatitis (AD). Patients were treated bid for 1 year, as needed, with pimecrolimus cream 1% in an open-label, non-controlled study. No indication of drug accumulation was found; pimecrolimus blood concentrations were consistently low, ranging from below the limit of quantitation (0.1 ng/ml) to 1.94 ng/ml. Treatment over this prolonged period was well tolerated, with no evidence of any treatment-related adverse events. The results of this 1-year study indicate that long-term management of AD with pimecrolimus cream 1% is associated with consistently very low systemic absorption, even in the youngest patients with extensive disease.     

The role of pimecrolimus cream 1% (Elidel)) in managing adult atopic eczema

In approximately 60% of patients atopic eczema starts in early childhood and persists throughout adolescence. The inadequate treatment of adult patients with recurrent flaring atopic eczema is associated with poor symptom control and diminished quality of life. The prolonged continuous use of topical corticosteroids is not advocated because of the risk of local and systemic adverse events. Pimecrolimus cream 1% (Elidel) is an alternative to topical corticosteroids, particularly for delicate skin, e.g. face and other sensitive skin areas, because it has no atrophogenic potential. The results from clinical trials in adult patients demonstrate that intermittent treatment with pimecrolimus relieves the acute symptoms of atopic eczema and improves disease control and quality of life in the long term.     

Pimecrolimus 1% cream (Elidel) for atopic dermatitis

Pimecrolimus is an immunomodulating medication that inhibits production of inflammatory cytokines in the skin and this compound was specifically developed for the treatment of inflammatory skin diseases. Phase II and III clinical trials with the topical formulation of pimecrolimus (Elidel cream, Novartis) have shown that it is safe and effective for use in patients with atopic dermatitis (AD). The US FDA recently approved Elidel for use in patients >or=2 years of age and older with mild to moderate atopic dermatitis (AD).     

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.     

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.     

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).     

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.     

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.     

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.