文献简介

出版社:Pediatr Drugs

作  者:Warner W. Carr

编  号:10.1007/s40272-013-0013-9

关键字:

年  份:2013   点击量:794

文献摘要 全文翻译

Abstract

摘要

Atopic dermatitis (AD) is an inflammatory skin disease commonly affecting children and managed by pediatricians, primary care physicians, allergists, and dermatologists alike. For many years, the only available topical pharmacological treatment was topical corticosteroids. This changed in 2000–2001, when topical formulations of two calcineurin inhibitors (tacrolimus and pimecrolimus) were approved for short-term or chronic intermittent treatment of AD in patients ≥2 years of age, in whom other treatments have been ineffective or contraindicated. These topical calcineurin inhibitors (TCIs) quickly became a popular treatment option due at least in part to concerns over adverse events associated with prolonged topical corticosteroid use, especially in children. However, based on theoretical concerns about a possible risk of lymphoma associated with TCI use, a Boxed Warning was placed on both products in 2006. Since then, despite an extensive body of evidence, no causal relationship has been demonstrated between TCI use and an increased risk of lymphoma; however, the US FDA has concluded that a link cannot be ruled out. In fact, based on post-marketing surveillance of spontaneous, literature, and solicited reports, we report here that the lymphoma incidence in the topical pimecrolimus-exposed population is up to approximately 54-fold less than that seen in the general US population. This review summarizes the mechanism of action of TCIs, the factors that prompted the Boxed Warning, and recent TCI safety and efficacy data. Based on these data, both topical corticosteroids and TCIs should have defined roles in AD management, with TCIs favored for sensitive skin areas (e.g., face) and instances where topical corticosteroids have proven ineffective, thereby minimizing the risk of adverse effects with both drug classes.

特应性皮炎(AD)是一种炎症性皮肤疾病,通常影响儿童,主要由儿科医生、初级保健医生、过敏症专科医师、皮肤科医师以相似的方式进行治疗。多年以来,唯一可用的外用药物为外用皮质类固醇。但是这一现象在2000-2001年被打破了,两种钙调神经磷酸酶抑制剂(他克莫司和吡美莫司)的外用配方被批准用于治疗大于2岁AD患者的短期或长期间歇性治疗,这些患者对其他治疗方法无效或有禁忌。由于(至少在某种程度上)对长期使用外用皮质类固醇相关副作用的担忧,尤其是在儿童患者中,这些外用钙调磷酸酶抑制剂(TCI)迅速成为一种受欢迎的治疗药物。然而,基于理论上的有关使用TCI治疗与发生淋巴瘤的可能风险,2006年这两款产品上均印有一个黑框警告。此后尽管有大量的证据实体,但没有证据表明TCI的使用和淋巴瘤的风险增加之间存在因果关系,然而美国FDA认为不能排除它们之间存在某种联系。事实上,基于自发的上市后的监测、文献和征求报告,我们在这里报道了外用吡美莫司人群中的淋巴瘤发病率比普通美国人群中的发病率约少54倍。本文总结了TCI的作用机制,提出黑框警告的原因,以及近期的TCI安全性和有效性数据。基于这些数据,在AD的治疗中,外用皮质类固醇和TCI都应该有其特定的作用,TCI主要用于敏感性皮肤区域(如面部)和那些已被证明对外用皮质类固醇无效果的患者,从而最大限度地减少这两类药物不良反应的风险。