Papier Ariana, Strowd Lindsay C
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Department of Dermatology, Wake Forest Baptist Medical Center, Wake Forest University, Winston-Salem, NC, USA.
Drugs Context. 2018 Apr 3;7:212521. doi: 10.7573/dic.212521. eCollection 2018.
Atopic dermatitis is a chronic inflammatory skin condition that affects up to 20% of children and 3% of adults globally. Although topical corticosteroids are considered to be the first-line agents, they can be associated with cutaneous and systemic adverse effects. Since the early 2000s, two new classes of nonsteroid topical therapies, topical calcineurin inhibitors and phosphodiesterase 4 (PDE4) inhibitors, have been introduced and provide a safe treatment alternative.
We performed a search and review of clinical trials that examined the safety and efficacy of topical calcineurin inhibitors and PDE4 inhibitors. The search was conducted using the PubMed database as well as preselected keywords and filters. This review focuses on the safety and efficacy of each therapy.
Sixty-nine clinical trials identified in this study have demonstrated the efficacy and safety of topical calcineurin and a single novel PDE4 inhibitor in the treatment of atopic dermatitis. Topical calcineurin inhibitors have been shown to be effective in both achieving lesion clearance as well as reducing relapse when used long-term and proactively. Similarly, in clinical trials the PDE4 inhibitor showed success in lesion clearance and symptom management. All three therapies (pimecrolimus, tacrolimus, crisaborole) are associated with low systemic absorption. No clinical trials to date have shown an increased risk of systemic adverse events or malignancy such as lymphoma. The most commonly reported treatment-related adverse event across all three therapies was application-site discomfort, pain or pruritus. It is important to note that long-term studies are not yet available for the novel PDE4 inhibitor.
Topical calcineurin inhibitors provide a safe and effective alternative to topical corticosteroid use in the treatment of atopic dermatitis. Although the US Food and Drug Administration (FDA) black box warning for topical calcineurin inhibitors remains, studies have not shown an increased risk of malignancy. These warnings have caused a decline in use in favor of topical steroids. A novel PDE4 inhibitor has shown efficacy and safety in studies up to one year. Further long-term safety data is needed.
特应性皮炎是一种慢性炎症性皮肤病，全球高达20%的儿童和3%的成年人受其影响。尽管外用糖皮质激素被视为一线药物，但它们可能会引起皮肤和全身不良反应。自21世纪初以来，两类新型非甾体外用疗法，即外用钙调神经磷酸酶抑制剂和磷酸二酯酶4（PDE4）抑制剂已被引入，提供了一种安全的治疗选择。
我们对检验外用钙调神经磷酸酶抑制剂和PDE4抑制剂安全性和疗效的临床试验进行了检索和综述。检索使用了PubMed数据库以及预先选定的关键词和筛选条件。本综述重点关注每种疗法的安全性和疗效。
本研究中确定的69项临床试验已证明外用钙调神经磷酸酶抑制剂和一种新型PDE4抑制剂在治疗特应性皮炎方面的疗效和安全性。外用钙调神经磷酸酶抑制剂已被证明在长期主动使用时，在实现皮损清除以及减少复发方面均有效。同样，在临床试验中，PDE4抑制剂在皮损清除和症状管理方面取得了成功。所有三种疗法（吡美莫司、他克莫司、克立硼罗）全身吸收低。迄今为止，尚无临床试验表明全身不良事件或淋巴瘤等恶性肿瘤风险增加。所有三种疗法中最常报告的与治疗相关的不良事件是用药部位不适、疼痛或瘙痒。需要注意的是，新型PDE4抑制剂尚无长期研究。
外用钙调神经磷酸酶抑制剂为外用糖皮质激素治疗特应性皮炎提供了一种安全有效的替代方案。尽管美国食品药品监督管理局（FDA）对外用钙调神经磷酸酶抑制剂有黑框警告，但研究并未表明恶性肿瘤风险增加。这些警告导致其使用量下降，转而青睐外用糖皮质激素。一种新型PDE4抑制剂在长达一年的研究中已显示出疗效和安全性。需要进一步的长期安全性数据。
