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Are topical phosphodiesterase 4 inhibitors safe and effective as treatment of mild to moderate atopic dermatitis?
In this meta-analysis, 7 double-blind randomized clinical trials of topical phosphodiesterase 4 inhibitors vs vehicle treatment for 1869 patients with mild to moderate atopic dermatitis were included. Topical application of phosphodiesterase 4 inhibitors was associated with a statistically significant improvement in both target lesion score and investigators’ assessment of atopic dermatitis compared with the control vehicles.
Topical phosphodiesterase 4 inhibitors represent a new option for the management of atopic dermatitis.
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.
To evaluate the efficacy and safety of topical PDE4 inhibitors in mild to moderate AD.
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.
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.
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.
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Accepted for Publication: December 31, 2018.
Published Online: March 27, 2019. doi:10.1001/jamadermatol.2019.0008
Correction: This article was corrected on May 22, 2019, to fix an error in the description of a study that was included in the meta-anlaysis.
Open Access: This article is published under the JN-OA license and is free to read on the day of publication.
Corresponding Authors: Hua Wang, MD, PhD (firstname.lastname@example.org), and Xiao-yan Luo, MD, PhD, Department of Dermatology, Children’s Hospital, Chongqing Medical University, Chongqing 400014, China (email@example.com).
Author Contributions: Drs Wang and Luo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Yang and J. Wang contributed equally to this work.
Concept and design: X. Zhang, H. Wang, Luo.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Yang, H. Wang, Luo.
Critical revision of the manuscript for important intellectual content: J. Wang, X. Zhang, Y. Zhang, Qin, H. Wang, Luo.
Statistical analysis: Yang, J. Wang, X. Zhang, Y. Zhang, Qin, Luo.
Administrative, technical, or material support: Yang, J. Wang, X. Zhang, H. Wang, Luo.
Supervision: Yang, H. Wang, Luo.
Conflict of Interest Disclosures: None reported.
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