The Clinical Efficacy And Safty Of Proactive Management With 0.03% Tacrolimus For Children With Atopic Dermatitis

BackgroundAtopic dermatitis(AD) is a chronic, recurrent inflammatory skin disease, both pruritus and dry skin are the main characteristics. The pathogenesis of AD haven’t been explained entirely, both genetic and immune function defects may contribute to the inflammatory skin. About 60% of AD starting within 1 year old, part of the severe may persist into adulthood or for life. Because of the repeated relapse of AD, the treatment of children’s AD is a urgent problem for long. The traditional treatment consists of application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors when patient typically running in flares. The short term benefit of this method is well known, but long term relieve is still hard to reach. In recent years, some studies proved that clinically normal appearing skin in patients with AD is immunologically abnormal, therefore the maintenance treatment to decrease relapse is necessary. Tacrolimus ointment(trade name protopic)is macrolactam calcineurin inhibitors. Several long-term study abroad comfirmed that twice weekly application of tacrolimus showed significantly fewer flares with a significantly reduced duration of flares. The experiment employed parallel-group comparison, randomized method to study the valid of proactive management with twice weekly application of tacrolimus in the therapy of AD and assess its safety.ObjectiveTo assess the clinical validity and safety of half-year maintenance treatment phase followed with twice weekly application of tacrolimus 0.03% ointment of moderate to severe AD in children, and comparison method to conventional therapy, whether it can prolong the first flare time, reduce the number of flares and prolong the flare-free time.MethodsThis is a randomized-controlled trial. The study included 50 cases of aged 2-15 meets Williams standards for moderate to severe AD patients, The patients had mild (score≥3) to severe as defined by the scoring system of Rajka & Langeland. The study consisted of a first phase of maximum of 6 weeks and a subsequent disease control period(DCP) randomized of 6 months. In the first period, patient was applied tacrolimus ointment twice a day, and during the second phase the test group applied tacrolimus twice weekly to previously affected areas, if the patient experienced an exacerbation during this time [Investigator Global Assessment (IGA) score> 2], they entered the disease exacerbation(DE) period whereby they applied Protopic two times a day to affected areas for 1-6 weeks until the flare resolved before returning to their original randomized treatment. The control group applied the conventional remedies with Protopic, only when DE occurred they were treated. The primary endpoint was the time before the first flare and the NO. of disease exacerbations during the disease control period that needed a treatment.ResultsIn all 50 cases were brought into the first phase, and 42 cases completed the study.1.The time to first DE:test group the time to first DE was significantly longer than the control group (mean±SD:105±66 vs 41±48; P=0.001, log-rank test).As the COX regression model shows, test group first time to recurrence was 4 times higher risk long than control group(P<0.001),and the less severity the longer to first DE (P=0.002)2.The number of DEs:The primary endpoint analysis showed that twice-weekly proactive used tacrolimus ointment significantly reduced the number of DEs needing substantial remedial intervention (1±0.85、 2.69±1.84, P<0.05)3.DE of second phase:Patients in the proactive group required fewer treatment days for exacerbation (51±25、16±17, P<0.05)4.Objective and subjective scores:on 2 weeks and 2 months control group EASI、IGA、VAS value was significantly higher than the test group (P<0.05).But there were no significant difference in EASI、IGA、VAS score on 4 months and 6 months (P>0.05)5.Effective rates and recurrence rates:the effective rates on 2 weeks and 2 months test group was higher than control group (95.6%vs56.5%; 100%vs65.2%, P<0.05),the recurrence rates lower than control group (0.0%vs39.1%;8.6%vs43.5%,P< 0.05). Both effective rates and recurrence rates between the test group and control group had no significant difference on day 4 months and 6 months (P>0.05)ConclusionApplicating 0.03% tacrolimus ointment twice a week proactively over half year was efficient for children in preventing, reducing DEs, prolonging the flare-free time and the period to the first flare.