Postępy Dermatologii i Alergologii

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3/2026 vol. 43
Review paper

Efficacy and safety of PDE4 inhibitor monotherapy in adult patients with atopic dermatitis: a systematic review and meta-analysis

Boyang Zhou 1
,
Liyuan Sun 1
,
Jiannan Xu 1
,
Xiaoyang Wang 1

  1. Department of Dermatology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

Adv Dermatol Allergol 2026; XLIII (3): 246–252

DOI: https://doi.org/10.5114/ada.2026.162759
Data publikacji online: 2026/07/19
Article files
PDIA Efficacy.pdf Efficacy and safety of PDE4 Supplementary Table S2.pdf Efficacy and safety of PDE4 Supplementary Table S1.pdf Efficacy and safety of PDE4 Supplementary material. Search strategies.pdf Efficacy and safety of PDE4 Supplemental Figures.pdf
  1. Liu D, Hu BD, Glickman J, et al. Artificial intelligence in atopic dermatitis: a narrative review. J Allergy Clin Immunol 2025; 156: 889-98.
  2. Yang G, Seok JK, Kang HC, et al. Skin barrier abnormalities and immune dysfunction in atopic dermatitis. Int J Mol Sci 2020; 21: 2867.
  3. Nakayama T, Hirahara K, Onodera A, et al. Th2 cells in health and disease. Annu Rev Immunol 2017; 35: 53-84.
  4. Olsson A, Steel K, Cooper R, et al. Methotrexate and ciclosporin both reduce levels of circulating IL-4 and IL-13 expressing CD4+ memory T-cells in childhood atopic dermatitis. Clin Exp Dermatol 2025; 50: 2249-54.
  5. Paes D, Schepers M, Rombaut B, et al. The molecular biology of phosphodiesterase 4 enzymes as pharmacological targets: an interplay of isoforms, conformational states, and inhibitors. Pharmacol Rev 2021; 73: 1016-49.
  6. Du B, Luo M, Ren C, Zhang J. PDE4 inhibitors for disease therapy: advances and future perspective. Future Med Chem 2023; 15: 1185-207.
  7. Takahashi K, Miyake K, Ito J, et al. Topical application of a PDE4 inhibitor ameliorates atopic dermatitis through inhibition of basophil IL-4 production. J Invest Dermatol 2024; 144: 1048-57.e8.
  8. Kim M, Del Duca E, Cheng J, et al. Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin. J Am Acad Dermatol 2023; 89: 283-92.
  9. Tsuji G, Hashimoto-Hachiya A, Yumine A, et al. PDE4 inhibition by difamilast regulates filaggrin and loricrin expression via keratinocyte proline-rich protein in human keratinocytes. J Dermatol Sci 2023; 110: 61-8.
  10. Saeki H, Ito K, Yokota D, Tsubouchi H. Difamilast ointment in adult patients with atopic dermatitis: a phase 3 randomized, double-blind, vehicle-controlled trial. J Am Acad Dermatol 2022; 86: 607-14.
  11. Saeki H, Baba N, Ito K, et al. Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial. Br J Dermatol 2022; 186: 40-9.
  12. Saeki H, Imamura T, Yokota D, Tsubouchi H. Difamilast ointment in Japanese adult and pediatric patients with atopic dermatitis: a phase III, long-term, open-label study. Dermatol Ther 2022; 12: 1589-601.
  13. Martín-Santiago A, Puig S, Arumi D, Laserna FJR. 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 2022; 96: 100679.
  14. Zhou B, Chen M, Shang S, Zhao J. Association of CTLA-4 gene polymorphisms and alopecia areata: a systematic review and meta-analysis. Biomarkers 2022; 27: 338-48.
  15. Zhou X, Li YZ. Clinical efficacy and safety analysis of sequential topical treatment with crisaborole ointment and fluticasone propionate cream for mild to moderate atopic dermatitis in the elderly. Chin J Med 2024; 59: 1033-5.
  16. Furue M, Kitahara Y, Akama H, et al. Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial. J Dermatol 2014; 41: 577-85.
  17. Ohba F, Matsuki S, Imayama S, et al. Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: an investigator-blinded, vehicle-controlled study. J Dermatolog Treat 2016; 27: 467-72.
  18. Samrao A, Berry TM, Goreshi R, Simpson EL. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol 2012; 148: 890-7.
  19. Simpson EL, Imafuku S, Poulin Y, et al. A phase 2 randomized trial of apremilast in patients with atopic dermatitis. J Invest Dermatol 2019; 139: 1063-72.
  20. Liu Z, Liu M, Cao Z, et al. Phosphodiesterase‑4 inhibitors: a review of current developments (2013-2021). Expert Opin Ther Pat 2022; 32: 261-78.
  21. Yang H, Wang J, Zhang X, et al. Application of topical phosphodiesterase 4 inhibitors in mild to moderate atopic dermatitis: a systematic review and meta-analysis. JAMA Dermatol 2019; 155: 585-93.
  22. Eichenfield LF, Serrao R, Prajapati VH, et al. Efficacy and safety of once-daily roflumilast cream 0.05% in pediatric patients aged 2-5 years with mild-to-moderate atopic dermatitis (INTEGUMENT-PED): a phase 3 randomized controlled trial. Pediatr Dermatol 2025; 42: 296-304.
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