Topical Phosphodiesterase 4 Inhibitors Successful in Atopic Dermatitis

Atopic dermatitis on arm
Researchers sought to investigate the safety and tolerability of topical PDE4 inhibitors vs vehicle in treating atopic dermatitis.

Topical phosphodiesterase 4 (PDE4) inhibitors vs vehicle as treatment for atopic dermatitis show no differences in emergent adverse events or the occurrence of serious emergent adverse events, according to data from a review and meta-analysis published in Current Therapeutic Research, Clinical and Experimental. PDE4 inhibitors showed a statistically significant reduced occurrence of exacerbation in atopic dermatitis and a significant risk for producing pain in studies with a low risk for bias.

Researchers sought to investigate the safety and tolerability of topical PDE4 inhibitors vs vehicle in treating atopic dermatitis. Crisaborole, cipamfylline and investigational drugs including difamilast were included in the study.

They conducted a systematic review and meta-analysis of Medline/PubMed, Web of Science, and Cochrane Library databases on September 27, 2021 (with no language restriction) that revealed 14 clinical trials that met analysis criteria. The majority of studies included pediatric and adult patients (age range, 2-79 years) with mild to moderate atopic dermatitis. Analysis revealed that topical treatment with PDE4 inhibitors showed no difference from vehicle treatment in global treatment emergent adverse events (TEAEs) (relative risk [RR] =0.99; 95% CI, 0.87-1.14; P =.94) or in serious emergent adverse events occurrence (RR = 0.92; 95% CI, 0.39-2.20; P =.86).

In studies with low risk of bias, PDE4 inhibitors compared with the vehicle showed a reduced rate of atopic dermatitis exacerbation (RR =0.62; 95% CI, 0.39-0.98; P =.04), and a significant risk for pain at the site of application (RR =2.59; 95% CI, 1.27-5.28; P =.01). There were no statistically significant differences noted in the occurrence of TEAEs related to pruritus, or skin and subcutaneous tissue disorders.

Study limitations include a shortage of randomized controlled trials and failure to perform clinical trial selection according to accepted principles for systematic reviews.

Researchers concluded that, “PDE4 inhibitors did not show differences from vehicle treatment in treatment emergent adverse events or serious emergent adverse events incidence.” In studies with low risk for bias, they affirmed that, “PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis exacerbation.”

Editor’s Note: This article was updated on August 10, 2022.

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Martín-Santiago A, Puig S, Arumi D, Rebollo Laserna FJ. Safety profile and tolerability of topical phosphodiesterase 4 inhibitors for the treatment of atopic dermatitis: a systematic review and meta-analysis. Curr Ther Res Clin Exp. Published online June 23, 2022. doi:10.1016/j.curtheres.2022.100679