» Articles » PMID: 35846836

Safety Profile and Tolerability of Topical Phosphodiesterase 4 Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis

Overview
Specialty Pharmacology
Date 2022 Jul 18
PMID 35846836
Authors
Affiliations
Soon will be listed here.
Abstract

Objective: Evaluate the safety profile and tolerability of topical phosphodiesterase 4 (PDE4) inhibitors versus vehicle as treatment for atopic dermatitis in published studies.

Methods: A search was performed in Medline/PubMed, Web of Science, and Cochrane Library databases on September 27, 2021, by 1 evaluator, without restrictions on publication dates or languages. Terms such as , and were included. The database searches were carried out by 1 evaluator. The titles and abstracts were reviewed for the identification and evaluation of potentially eligible studies. Study selection was made by two reviewers, so there was no intra-examiner statistic at the study selection step. The full-text articles were reviewed to determine whether or not they would be included in the systematic review. Global analyses, which included studies with both unclear and low risk of bias and subanalyses of studies with a low risk of bias were performed.

Results: 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 (relative risk = 0.99; 95% CI, 0.87-1.14;  = 0.94) or in serious emergent adverse events appearance (relative risk = 0.92; 95% CI, 0.39-2.20;  = 0.86). In subanalyses of studies with a low risk of bias, a reduced rate of atopic dermatitis exacerbation was observed in PDE4 inhibitors compared with the vehicle (relative risk = 0.62; 95% CI, 0.39-0.98;  = 0.04) and risk of pain at the application site was confirmed (relative risk = 2.59; 95% CI, 1.27-5.28;  = 0.01).

Conclusions: 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 of bias, PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis exacerbation.

Citing Articles

The role of aryl hydrocarbon receptor agonists in the treatment of vitiligo.

Bitterman D, Kabakova M, Wang J, Collins A, Patel P, Gupta N Arch Dermatol Res. 2024; 316(9):659.

PMID: 39369105 DOI: 10.1007/s00403-024-03405-2.


Topical anti-inflammatory treatments for eczema: network meta-analysis.

Lax S, Van Vogt E, Candy B, Steele L, Reynolds C, Stuart B Cochrane Database Syst Rev. 2024; 8():CD015064.

PMID: 39105474 PMC: 11301992. DOI: 10.1002/14651858.CD015064.pub2.


A Comprehensive Review of Phototherapy in Atopic Dermatitis: Mechanisms, Modalities, and Clinical Efficacy.

Molla A Cureus. 2024; 16(3):e56890.

PMID: 38665759 PMC: 11043791. DOI: 10.7759/cureus.56890.


Advancing Treatment in Atopic Dermatitis: A Comprehensive Review of Clinical Efficacy, Safety, and Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, and Phosphodiesterase-4 Inhibitors as Topical Therapies.

Hernandez T, Aleman S, Bao-Loc-Trung M, Forte M, Brandt W, Armstrong C Cureus. 2024; 16(3):e55393.

PMID: 38562326 PMC: 10982833. DOI: 10.7759/cureus.55393.


The immunological and structural epidermal barrier dysfunction and skin microbiome in atopic dermatitis-an update.

Cetinarslan T, Kumper L, Folster-Holst R Front Mol Biosci. 2023; 10:1159404.

PMID: 37654796 PMC: 10467310. DOI: 10.3389/fmolb.2023.1159404.


References
1.
Abedz N, Pawliczak R . Efficacy and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis: meta-analysis of randomized clinical trials. Postepy Dermatol Alergol. 2020; 36(6):752-759. PMC: 6986278. DOI: 10.5114/ada.2019.91425. View

2.
Schmitt J, von Kobyletzki L, Svensson A, Apfelbacher C . Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol. 2010; 164(2):415-28. DOI: 10.1111/j.1365-2133.2010.10030.x. View

3.
Ring J, Mohrenschlager M, Henkel V . The US FDA 'black box' warning for topical calcineurin inhibitors: an ongoing controversy. Drug Saf. 2008; 31(3):185-98. DOI: 10.2165/00002018-200831030-00001. View

4.
Kucharekova M, Hornix M, Ashikaga T, Tkint S, de Jongh G, Schalkwijk J . The effect of the PDE-4 inhibitor (cipamfylline) in two human models of irritant contact dermatitis. Arch Dermatol Res. 2003; 295(1):29-32. DOI: 10.1007/s00403-003-0389-4. View

5.
Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Esp Cardiol (Engl Ed). 2021; 74(9):790-799. DOI: 10.1016/j.rec.2021.07.010. View