Nathalie Barbier

Safety and Tolerability of 1% Pimecrolimus Cream Among Infants: Experience With 1133 Patients Treated for Up to 2 Years

Pimecrolimus is a calcineurin inhibitor developed for the topical treatment of atopic dermatitis. During the clinical development of 1% pimecrolimus cream, 1133 patients 3 to 23 months of age with mild to severe atopic dermatitis were treated for up to 2 years. The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants, on the basis of the combined results from all studies (4 pharmacokinetic studies and 6 clinical trials) conducted among these patients. Pimecrolimus blood concentrations measured for 35 patients were consistently low (≤1 ng/mL in >80% of samples), irrespective of the disease severity and extent, and remained low during intermittent treatment for up to 1 year. The level of systemic exposure to pimecrolimus among infants was comparable to that observed for older pediatric patients enrolled in the same studies and treated in the same way with 1% pimecrolimus cream, which indicated that young pediatric patients are not at higher risk of significant percutaneous absorption of topically applied pimecrolimus, despite their large skin surface area/body mass ratio. The 6 clinical trials included a total of 1098 infants, who were treated for periods ranging from 4 weeks to 2 years. Most of these patients (60%) had moderate to severe disease at baseline. The most frequently reported adverse events were common childhood disorders such as nasopharyngitis, pyrexia, upper respiratory tract infections, ear infections, and bronchitis. During the double-blind (DB) studies or DB phases of studies, the incidence rates for the most frequently reported adverse events were similar for patients who received 1% pimecrolimus cream and patients who received the vehicle, except for the incidence of teething, which was higher among the pimecrolimus-treated infants (relative risk: 2.02; 95% confidence interval: 1.32–3.27). Treatment with 1% pimecrolimus cream was not associated with an increase in the overall incidence of nonskin infections, compared with the vehicle (relative risk: 1.015; 95% confidence interval: 0.88–1.18). The incidence density (ID) rates for total bacterial, fungal, parasitic, and viral skin infections during the DB studies or DB phases of studies were comparable for patients treated with 1% pimecrolimus cream and patients who received the vehicle. The ID rate of herpes simplex virus infections was 0.8 cases per 1000 patient-months of follow-up monitoring among patients treated with 1% pimecrolimus cream and 1.7 cases per 1000 patient-months of follow-up monitoring among patients who received the vehicle. Considering all 1098 infants treated with 1% pimecrolimus cream in DB trials and open-label studies, the ID rate of clinically diagnosed eczema herpeticum was 1.3 cases per 1000 patient-months of follow-up monitoring. Burning and erythema were the most frequently reported application site reactions, with ID rates of 2.0 and 1.2 cases per 1000 patient-months of follow-up monitoring, respectively. No sign of immunosuppression was found among infants treated intermittently with 1% pimecrolimus cream for up to 2 years; they demonstrated normal immune responses to vaccinations and did not show increases in the incidence of systemic infections or skin infections over time.

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.

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.

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.

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.