Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis
Application of Topical Phosphodiesterase 4 Inhibitors in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta-analysis
复制标题
DOI：
10.1001/jamadermatol.2019.0008
复制
发表时间：
2019-05
期刊：
影响因子：
10.9
通讯作者：
Huan Yang;Ji Wang;Xin Zhang;Yan Zhang;Zi-Li Qin;Hua Wang;Xiaogang Luo
中科院分区：
文献类型：
--
作者：
Huan Yang;Ji Wang;Xin Zhang;Yan Zhang;Zi-Li Qin;Hua Wang;Xiaogang Luo
重要性 外用药物是特应性皮炎 (AD) 患者的主要治疗方法，但选择有限。磷酸二酯酶 4 (PDE4) 抑制剂是 AD 治疗的新候选药物。目的评价局部PDE4抑制剂治疗轻中度AD的疗效和安全性。数据来源 临床试验从MEDLINE、Embase、Cochrane对照试验注册库、中国医学数据库（万方、中国国家知识基础设施、中国生物医学文献数据库和中国科技期刊数据库）、ClinicalTrials.gov和其他试验注册库中获取，从开始到2018年8月15日。不存在语言限制。研究选择 仅纳入针对轻度至中度 AD 患者的局部 PDE4 抑制剂与局部赋形剂治疗的双盲随机临床试验。数据提取和综合 两名评审员独立提取研究特征、干预细节和结果。使用随机效应模型进行荟萃分析。使用 Cochrane 协作组织的偏倚风险评估工具来评估偏倚风险。漏斗图和 Egger 检验用于评估发表偏倚。主要结果和措施 目标病变评分相对于基线的变化以标准化平均差 (SMD) 和 95% CI 表示。研究人员的评估和安全性结果以 95% CI 的相对风险表示。结果 共确定了 7 项研究，其中包括 1869 名轻度至中度 AD 患者。总体而言，与局部媒介物对照相比，局部应用 PDE4 抑制剂与目标病变评分显着下降相关（SMD -0.40；95% CI，-0.61 至 -0.18；P < .001），并且研究者对透明或几乎透明皮肤的评估有较高的反应率（相对风险，1.50；95% CI，1.33-1.70；P < .001）。 .001）。与治疗相关的不良事件或需要停止治疗的不良事件没有差异。亚组分析表明，PDE4抑制剂治疗14天和28天后，目标病变评分显着下降。然而，这些有益效果仅对 PDE4 抑制剂 crisaborole 和 AN2898 显示（crisaborole 第 14 天：SMD，-0.59；95% CI，-1.15 至 -0.02；P = 0.04；AN2898 第 14 天：SMD，-0.76；95% CI，-1.38 至 -0.13；P = .02；第 28 天的克立硼罗：SMD，-0.86；95% CI，-1.44 至 -0.28；P = .004；第 28 天的 AN2898：SMD，-0.68；P = .03；各项研究之间的异质性并不显着。结论和相关性 这项荟萃分析表明，局部 PDE4 抑制剂是治疗轻度至中度 AD 的安全有效的方法。目前的证据支持使用 crisaborole 或 AN2898 作为轻至中度 AD 的维持或序贯治疗的选择。
Importance Topical medication is the central treatment for patients with atopic dermatitis (AD), but the options are limited. Phosphodiesterase 4 (PDE4) inhibitors are a new candidate for AD therapy. Objective To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD. Data Sources Clinical trials were identified from MEDLINE, Embase, Cochrane Controlled Register of Trials, Chinese medical databases (Wanfang, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database), ClinicalTrials.gov, and other trial registries from inception to August 15, 2018. No restrictions on languages were placed. Study Selection Only double-blind randomized clinical trials with topical PDE4 inhibitors vs topical vehicle treatment for patients with mild to moderate AD were included. Data Extraction and Synthesis Two reviewers independently extracted study features, intervention details, and outcomes. A meta-analysis was performed using the random-effects model. The Cochrane Collaboration’s risk of bias assessment tool was used to assess the risk of bias. Funnel plots and Egger tests were used to assess the publication bias. Main Outcomes and Measures Changes from baseline in target lesion score were expressed in terms of standardized mean differences (SMDs) with 95% CIs. Outcomes of investigators’ assessment and safety were expressed in terms of relative risk with 95% CIs. Results Seven studies were identified, which included 1869 patients with mild to moderate AD. Overall, compared with the topical vehicle control, topical application of PDE4 inhibitors was associated with a significant decrease in target lesion score (SMD −0.40; 95% CI, −0.61 to −0.18; P < .001) and a higher response rate in investigators’ assessment of clear or almost clear skin (relative risk, 1.50; 95% CI, 1.33-1.70; P < .001). There was no difference in treatment-related adverse events or in adverse events that required discontinuation of therapy. Subgroup analyses indicated that after 14 and 28 days of therapy with PDE4 inhibitors, target lesion score was significantly decreased. However, these beneficial effects were displayed only for the PDE4 inhibitors crisaborole and AN2898 (crisaborole at day 14: SMD, −0.59; 95% CI, −1.15 to −0.02; P = .04; AN2898 at day 14: SMD, −0.76; 95% CI, −1.38 to −0.13; P = .02; crisaborole at day 28: SMD, −0.86; 95% CI, −1.44 to −0.28; P = .004; AN2898 at day 28: SMD, −0.68; 95% CI, −1.30 to −0.05; P = .03). Heterogeneity was not significant across studies. Conclusions and Relevance This meta-analysis suggests that topical PDE4 inhibitors are a safe and effective treatment for mild to moderate AD. Current evidence supports the use of crisaborole or AN2898 as the choice of maintenance or sequential therapy for mild to moderate AD.