Fröschl Barbara, Arts Danielle, Leopold Christine
Gesundheit Österreich GmbH, Geschäftsbereich ÖBIG, Wien, Österreich.
GMS Health Technol Assess. 2007 Sep 20;3:Doc09.
In developed countries 2.5% of the population - mainly children - are affected by atopic dermatitis. During the past few years its prevalence amongst school children has risen decisively and now lies between 8% to 16%. It is the most frequent chronic skin disease amongst school-aged children.
Current methods of treating atopic dermatitis among children focus on containing and preventing the illness's further progression. Preventing dry skin, relieving symptoms (such as pruritis and inflammation of the skin) and identifying and avoiding provocating factors are elementary goals of treatment. Successful treatment can substantially increase the children's quality of life. Possible therapies of children affected by atopic dermatitis include both topically and systemically applied pharmaceuticals. During the past ten years the use of corticosteroids has been the standard topical anti-inflammatory therapy in case of aggravating inflammations. In 2002 a new group of pharmaceutical substances (topical calcineurin inhibitors tacrolimus and pimecrolimus) was authorised in Germany for topical anti-inflammatory treatment of patients. Because of its high prevalence atopic dermatitis represents a major expense factor to the German health care system. In 1999 the costs of the treatment of atopic dermatitis with corticosteroids in Germany amounted to 230 million Euro. If other direct costs for the treatment are included, for example hospitalisation or doctor appointments, the total costs amount to 3.57 billion Euro.
How effective and efficient are topical anti-inflammatory treatments of children with atopic dermatitis?
A systematic literature search was performed in 35 international databases which yielded 1335 articles. Following a two-part selection process according to predefined criteria 24 publications were included in the assessment.
Of 19 randomised controlled clinical trials, which were included in the assessment, only two evaluated the effect of topical corticosteroids in comparison to tacrolimus, which is one of the calcineurin inhibitors. Both studies show that tacrolimus is more effective than hydrocortisone acetate in children with moderate to severe atopic dermatitis. No study was found that directly compares corticosteroids with pimecrolimus in the treatment of paediatric patients with atopic dermatitis. However, two trials show that an intermittent treatment with pimecrolimus can reduce the need for topical corticosteroids. Two publications focusing on the costs of atopic dermatitis, provide model calculations comparing the use of topical corticosteroids and calcineurin inhibitors. The calculations show that the treatment with topical corticosteroids is inferior to the treatment with pimecrolimus in children with mild to moderate atopic dermatitis. Furthermore the treatment with tacrolimus appears to be more expensive however also more effective in comparison to topical corticosteroids.
During the past five decades topical corticosteroids have represented the first choice therapy when it comes to atopic dermatitis. Their effectiveness has been proven by several studies. Amongst newer generations of topical corticosteroids the occurrence of adverse side effects seems to be less frequent. Due to the fact that they have only recently been authorised experience with tacrolimus and pimecrolimus is limited. So far the only adverse side effect of the calcineurin inhibitors appears to be a burning sensation of the skin. One point for discussion concerns the economical aspects of the treatment of atopic dermatitis. The cost-effectiveness of pimecrolimus has been based on the calculated costs per quality-adjusted life year, which were lower than the frequently hawked value of 50,000 USD. It is up to policy makers to decide on the actual value of a quality-adjusted life year.
CONCLUSIONS/RECOMMENDATIONS: From a medical as well as an economical viewpoint, there appears to be insufficient evidence stating that inflammatory steroid-free substances are more effective and/or efficient than topical corticosteroids. Based on the results of the studies that have been included in this assessment therapies based on calcineurin inhibitors seem to constitute a good alternative in case a child is unresponsive or intolerable to topical corticosteroids and for the treatment of intertriginous areas.
在发达国家，2.5%的人口（主要是儿童）患有特应性皮炎。在过去几年中，学龄儿童中该病的患病率显著上升，目前在8%至16%之间。它是学龄儿童中最常见的慢性皮肤病。
目前治疗儿童特应性皮炎的方法主要集中在控制和预防病情的进一步发展。预防皮肤干燥、缓解症状（如瘙痒和皮肤炎症）以及识别和避免诱发因素是治疗的基本目标。成功的治疗可以显著提高儿童的生活质量。治疗受特应性皮炎影响儿童的可能疗法包括局部和全身应用的药物。在过去十年中，皮质类固醇的使用一直是炎症加重时的标准局部抗炎疗法。2002年，一组新的药物（局部钙调神经磷酸酶抑制剂他克莫司和吡美莫司）在德国被批准用于患者的局部抗炎治疗。由于特应性皮炎的高患病率，它是德国医疗保健系统的一个主要费用因素。1999年，德国用皮质类固醇治疗特应性皮炎的费用达2.3亿欧元。如果包括其他治疗的直接费用，如住院或看医生，总费用达35.7亿欧元。
儿童特应性皮炎局部抗炎治疗的有效性和效率如何？
在35个国际数据库中进行了系统的文献检索，共获得1335篇文章。根据预定义标准进行两部分选择过程后，24篇出版物被纳入评估。
在纳入评估的19项随机对照临床试验中，只有两项评估了局部皮质类固醇与钙调神经磷酸酶抑制剂之一他克莫司相比的效果。两项研究均表明，他克莫司在中度至重度特应性皮炎儿童中比醋酸氢化可的松更有效。未发现直接比较皮质类固醇与吡美莫司治疗儿童特应性皮炎的研究。然而，两项试验表明，吡美莫司间歇治疗可减少局部皮质类固醇的使用需求。两篇关注特应性皮炎费用的出版物提供了比较局部皮质类固醇和钙调神经磷酸酶抑制剂使用的模型计算。计算表明，在轻度至中度特应性皮炎儿童中，局部皮质类固醇治疗不如吡美莫司治疗。此外，与局部皮质类固醇相比，他克莫司治疗似乎更昂贵，但也更有效。
在过去五十年中，局部皮质类固醇一直是特应性皮炎的首选治疗方法。其有效性已得到多项研究证实。在新一代局部皮质类固醇中，不良反应的发生率似乎较低。由于他克莫司和吡美莫司最近才被批准使用，相关经验有限。到目前为止，钙调神经磷酸酶抑制剂唯一的不良反应似乎是皮肤烧灼感。一个讨论点涉及特应性皮炎治疗的经济方面。吡美莫司的成本效益是基于每质量调整生命年的计算成本，该成本低于经常宣传的50000美元的价值。质量调整生命年的实际价值由政策制定者决定。
结论/建议：从医学和经济角度来看，似乎没有足够的证据表明无炎症类固醇物质比局部皮质类固醇更有效和/或更高效。基于本评估中纳入的研究结果，对于对局部皮质类固醇无反应或不耐受的儿童以及间擦部位的治疗，基于钙调神经磷酸酶抑制剂的疗法似乎是一个很好的选择。
