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.     

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.     

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%) 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.     

Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients

BACKGROUND AND OBJECTIVE: Pimecrolimus cream 1% is an effective treatment for atopic eczema. The aim was to investigate its efficacy in asteatotic eczema, a skin disease similar to atopic eczema and its associated dry skin and itching. METHODS: Single-centre, randomized, double-blind, vehicle controlled study in 40 patients with asteatotic eczema. Efficacy was assessed by eczema area and severity index (EASI), investigators global assessment (IGA), patient's self-assessment, and pruritus severity. RESULTS: After 4 weeks of treatment, EASI, the primary efficacy variable, was reduced by 62+/-7% from baseline in patients on pimecrolimus, compared to 21+/-14% in patients on vehicle (P=0.013). With pimecrolimus there was also a better control of pruritus (P=0.042) at week 4 whereas a better control of disease according to self-assessment could only be observed at weeks 2 (P=0.01) and week 3 (P=0.08). CONCLUSION: Pimecrolimus cream 1% is effective in patients with asteatotic eczema.     

An experimental ointment formulation of pimecrolimus is effective in psoriasis without occlusion

Pimecrolimus (Elidel, SDZ ASM 981), a new macrolactam ascomycin derivative, was highly effective in treating plaque-type psoriasis when applied under Finn-chamber occlusion. A two-centre, randomized, double-blind, vehicle- and positive-controlled within-patient study was therefore conducted in 23 adult psoriasis patients. Pimecrolimus 1% was applied, twice daily, in an experimental ointment formulation, along with the corresponding vehicle, 0.005% calcipotriol ointment and 0.05% clobetasol-17-propionate ointment to test sites without occlusion for 21 days. Erythema, induration and scaling (score: 0 [absent] to 4 [severe]) were evaluated. The total sign score was defined as the sum of the erythema, induration and scaling scores (range 0-12). Pimecrolimus 1% ointment was significantly (p = 0.03) more effective than the corresponding vehicle, with an improvement in total sign score of 51.4% compared with 36.7% for the corresponding vehicle. Improvements with calcipotriol and clobetasol-17-propionate were 71.5% and 88.3%, respectively. No local or systemic drug-related side effects were observed in the study. We conclude that pimecrolimus 1% in the experimental ointment formulation was significantly more effective than its corresponding vehicle, but less effective than calcipotriol and clobetasol ointment. This is the first study reporting a significant therapeutic effect of pimecrolimus in an ointment formulation applied without occlusion to psoriatic plaques.     

Anti-inflammatory effect of pimecrolimus in the sodium lauryl sulphate test

Background Pimecrolimus is a calcineurin inhibitor used for the topical treatment of inflammatory skin diseases. We have shown previously that pimecrolimus cream is not effective on intact skin in the ultraviolet erythema test. Objective To test the anti‐inflammatory effect of pimecrolimus cream after damage of the skin barrier by sodium lauryl sulphate (SLS) in a randomised, placebo‐controlled, observer‐blinded study. Methods SLS (3% v/v) was applied under occlusion on the back of 36 healthy volunteers for 24 h. Subsequently, the test areas were treated for 24 h with pimecrolimus cream, 1% hydrocortisone in a hydrophilic ointment, and the vehicle alone over three consecutive days. One control area remained untreated. The erythema index and the transepidermal water loss (TEWL) served as readout parameters to assess the SLS‐induced skin irritation. Results Pimecrolimus cream and 1% hydrocortisone cream significantly reduced the SLS‐induced erythema. The two test preparations did not have a significant effect on the TEWL. Conclusion After damage to the skin barrier by SLS, pimecrolimus seems to penetrate into the skin as shown by a reduction of the irritation‐induced erythma. These data further support the notion that pimecrolimus is selectively effective in the treatment of skin disorders with an impaired function of the epidermal barrier.     

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.     

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.     

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.     

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).     

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.     

Treatment of oral erosive lichen planus with 1% pimecrolimus cream: a double-blind, randomized, prospective trial with measurement of pimecrolimus levels in the blood

OBJECTIVES: To evaluate the efficacy of 1% pimecrolimus cream in treating oral erosive lichen planus and to assess its tolerance. DESIGN: Double-blind randomized trial with placebo control. SETTING: Outpatients of the Department of Dermatology, University Hospital of Nice, from December 21, 2004, to April 19, 2005. PATIENTS: Fourteen consecutive patients with oral erosive lichen planus confirmed by histological examination and with a clinical score superior to 3. Of the 14 patients, 2 did not meet the inclusion criteria and 12 were enrolled in the trial. INTERVENTION: The intervention was 1% pimecrolimus cream or its vehicle, which was applied on ulcerated lesions twice a day for 4 weeks. MAIN OUTCOME MEASURES: The efficacy of the treatment was quantified using a 12-point clinical score. The blood level of pimecrolimus was analyzed on days 0 (baseline), 14, and 28. RESULTS: In the placebo group, the mean score was 4.67 on day 0 vs 3.33 on day 28 (P = .22). In the pimecrolimus group, the mean score was 6.83 on day 0 vs 3.33 on day 28 (P = .04). In the pimecrolimus group, blood concentrations of pimecrolimus were always above the threshold (mean value, 2.84 ng/mL; extreme values, 0-6.19 ng/mL). Pimecrolimus cream was well tolerated, and only transient burning sensations were reported by some subjects. Each of the patients in the pimecrolimus group whose condition improved subsequently relapsed when assessed 1 month after treatment. CONCLUSIONS: The 1% pimecrolimus cream seems to be an effective and well-tolerated treatment for oral erosive lichen planus. The finding of systemic levels of pimecrolimus after mucosal applications necessitates long-term study because it seems that long-term application is required to maintain clinical improvement.     

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.     

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.     

A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open‐label clinical trial

Background. There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some reports have indicated beneficial effects of topical pimecrolimus. Aim. To compare the efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the treatment of patients with papulopustular rosacea (PR). Methods. A group of 49 patients with PR was investigated in this single‐centre, randomized, open‐label study. Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the inflammatory lesion count, the severity of facial erythema and telangiectasia, Physician’s Global Assessment (PGA), and safety and tolerability at baseline and at weeks 3, 6, 9 and 12. Results. In total, 48 patients completed the study. Both treatments were very effective in the treatment of PR. There were no significant differences between the treatments in inflammatory lesion counts, overall erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05). Neither treatment produced any clinically relevant improvement in telangiectasia. Conclusion. Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR.     

Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study

Background Erosive oral lichen planus (EOLP) is a T‐cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option. Objectives To investigate the efficacy of pimecrolimus cream 1% (Elidel^®) compared with vehicle cream in the treatment of EOLP. Methods Twenty patients were enrolled in a prospective, double‐blind, randomized, vehicle‐controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open‐label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts. Results Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP ‘composite score’ including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus‐treated group compared with vehicle (P = 0·025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long‐lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL^?1. Conclusions Pimecrolimus cream 1% effectively treats EOLP with long‐lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.     

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.     

Sustained efficacy and safety of pimecrolimus cream 1% when used long-term (up to 26 weeks) to treat children with atopic dermatitis

Abstract:  Atopic dermatitis is a chronic, inflammatory condition affecting up to 20% of children. Here, we report the long-term extension study of previously published pivotal phase III studies with pimecrolimus cream 1%. Two identical, 26-week studies (6-week, double-blind, followed by 20-week, open-label phases) were conducted in children aged 2 to 17 years with atopic dermatitis. Pooled efficacy and safety analyses were performed. At day 43, 34.8% pimecrolimus-treated patients versus 18.4% in the vehicle group (p < 0.001) were clear/almost clear (Investigators' Global Assessment 0/1) of disease, with significant differences (p < 0.05) between treatment groups for all double-blind visits in all parameters. Pimecrolimus was significantly more effective (based on the Eczema Area and Severity Index) in treating the face and neck versus the rest of the body (p < 0.0001) and versus vehicle (p < 0.0001) in the double-blind phase. Disease control was sustained in the pimecrolimus group throughout the whole study. Patients treated with vehicle during the double-blind phase experienced rapid, marked improvement when switched to pimecrolimus in the open-label phase. The incidence of adverse events was low and comparable between treatment groups. In conclusion, pimecrolimus cream 1% is effective and well tolerated in the long-term control of children with mild to moderately severe atopic dermatitis.     

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.