Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E, Giannetti A, Bieber T, Vyas J, Deleuran M
Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany.
Allergy. 2008 Jun;63(6):742-50. doi: 10.1111/j.1398-9995.2008.01683.x.
Long-term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent relapses. This 12-month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE).
During the initial open-label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of < or =2 was achieved, the patient entered the disease control period (DCP) and was randomized to either proactive tacrolimus (n = 116) or vehicle ointment (n = 108) twice weekly for 12 months. Exacerbations were treated with 0.1% tacrolimus ointment b.i.d. until an IGA < or =2 was regained, then randomized treatment was restarted. The primary endpoint was the number of DEs during the DCP that required a substantial therapeutic intervention.
Proactive tacrolimus 0.1% ointment application significantly reduced the number of DEs requiring substantial therapeutic intervention (median difference 2; P < 0.001; Wilcoxon rank sum test), the percentage of DE treatment days (median difference: 15.2%; P < 0.001; Wilcoxon rank sum test) and increased the time to first DE (median 142 vs 15 days; P < 0.001; stratified log-rank test). The adverse event profile was similar for the two treatment approaches.
A 12-month, twice weekly proactive tacrolimus ointment application was an effective treatment in most study patients which prevented, delayed and reduced the occurrence of AD exacerbations.
使用低剂量、间歇性外用抗炎药对特应性皮炎（AD）进行长期治疗可控制急性病情并预防复发。这项为期12个月的欧洲多中心随机研究调查了每周两次主动使用0.1%他克莫司软膏是否能使AD保持缓解状态并降低疾病加重（DE）的发生率。
在初始开放标签期，257例成年AD患者在受累区域每日两次（bid）涂抹0.1%他克莫司软膏，持续长达6周。当研究者整体评估（IGA）评分≤2时，患者进入疾病控制期（DCP），并被随机分为两组，一组每周两次主动使用他克莫司（n = 116），另一组使用赋形剂软膏（n = 108），持续12个月。病情加重时，每日两次使用0.1%他克莫司软膏治疗，直至IGA评分再次≤2，然后重新开始随机治疗。主要终点是在DCP期间需要进行大量治疗干预的DE次数。
主动使用0.1%他克莫司软膏显著减少了需要进行大量治疗干预的DE次数（中位数差异为2；P < 0.001；Wilcoxon秩和检验）、DE治疗天数的百分比（中位数差异：15.2%；P < 0.001；Wilcoxon秩和检验），并延长了首次出现DE的时间（中位数分别为142天和15天；P < 0.001；分层对数秩检验）。两种治疗方法的不良事件情况相似。
在大多数研究患者中，为期12个月、每周两次主动使用他克莫司软膏是一种有效的治疗方法，可预防、延缓并减少AD病情加重的发生。
