Safety Profile and Tolerability of Topical Phosphodiesterase 4 Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis
A. Martín‐Santiago, Susana Puig, Daniel Arumí, Francisco José Rebollo Laserna
Abstract
: Evaluate safety profile and tolerability of topical phosphodiesterase 4 (PDE4) inhibitors versus vehicle as treatment for atopic dermatitis in published studies. : Search was performed in Medline/PubMed, Web of Science, and Cochrane Library databases on September 27, 2021 by one evaluator, without restrictions on publication dates or languages. Terms such atopic dermatitis, phosphodiesterase 4 inhibitors, calcineurin inhibitors and randomized controlled trials were included. The database searches were carried out by one evaluator. The titles and abstracts were reviewed for the identification and evaluation of potentially eligible studies. Study selection was made by two reviewers, with no intra-examiner statistic at step. The full-text articles were reviewed to determine whether they would be included in the systematic review. Global analyses, which included studies with both unclear and low risk of bias and sub-analyses of studies with a low risk of bias were performed. : Out of 237 identified articles, 14 clinical trials were included in the meta-analysis. In global analyses of studies with low and unclear risk of bias, topical treatment with PDE4 inhibitors did not differ from vehicle treatment in global treatment emergent adverse events (TEAEs) (RR=0.99; 95%CI:0.87-1.14, p=0.94) or in serious emergent adverse events (SEAEs) appearance (RR=0.92; 95%CI:0.39-2.20, p=0.86). In sub-analyses of studies with a low risk of bias, a reduced rate of atopic dermatitis exacerbation was observed in PDE4 inhibitors compared to the vehicle (RR=0.62; 95%CI:0.39-0.98, p=0.04) and a risk of pain at the application site was confirmed (RR=2.59; 95%CI:1.27-5.28; p=0.01). : PDE4 inhibitors did not show differences from vehicle treatment in TEAE or SEAE incidence. In studies with low risk of bias, PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis exacerbation.