Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: Results of a randomized, multicentre, comparative study

Background: Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations. Objectives: This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. Patients and methods: During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of ≤ 2 was achieved, the patient entered the disease control period (DCP) and was randomized to receive tacrolimus (n = 125) or vehicle ointment (n = 125) twice weekly for 12 months. Exacerbations were treated with 0.03% tacrolimus ointment twice daily until an IGA ≤ 2 was regained, then randomized treatment was restarted. Results: The outcome measure was the number of DEs during the DCP that required substantial therapeutic intervention. Proactive application of 0.03% tacrolimus ointment significantly reduced the number of DEs during the DCP that required substantial therapeutic intervention (median difference: 1.0; P < 0.001; Wilcoxon rank-sum test), the percentage of DE treatment days (median difference: 6.2; P < 0.001; Wilcoxon rank-sum test), and increased the time to first DE requiring intervention (median: 173 vs. 38 days; P < 0.001; stratified log-rank test). Differences in quality of life scores were not significant between groups. The adverse event profile was similar for both treatment approaches. Conclusions: Twice-weekly proactive application of 0.03% tacrolimus ointment over 12 months was effective for most paediatric study patients in preventing, delaying and reducing the occurrence of AD exacerbations.