Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review

• Published in: Dermatology and therapy Vol. 13; no. 12; pp. 3031 - 3042
• Main Authors: Blauvelt, Andrew, Langley, Richard G., Gordon, Kenneth B., Silverberg, Jonathan I., Eyerich, Kilian, Sommer, Morten O. A., Felding, Jakob, Warren, Richard B.
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.12.2023; Springer; Adis, Springer Healthcare
• Subjects: Atopic dermatitis; B cells; Biological products; Biotechnology industry; Care and treatment; Dermatology; Drug therapy; Inflammation; Internal Medicine; Medical colleges; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Nerandomilast; Oral and Maxillofacial Surgery; Orismilast; PDE4 inhibitors; PDE4B; PDE4D; PF-07038124; Pharmaceutical industry; Plastic Surgery; Psoriasis; Quality of Life Research; Review; Roflumilast; Skin; United States; France; Switzerland; Germany; PDE4 inhibitors; PDE4D; Zatolmilast; PDE4B; PF-07038124; Orismilast; Nerandomilast
• ISSN: 2193-8210; 2190-9172
• DOI: 10.1007/s13555-023-01054-3

For decades, topical corticosteroids have been the mainstay of treatment for mild-to-moderate inflammatory skin diseases, even though only short-term use is approved for these agents and systemic inflammation is not addressed. Increased understanding of the immunopathogenesis of these conditions, especially for psoriasis and atopic dermatitis, has facilitated the development of antibody-based drugs that neutralize single key cytokines or their associated receptors, such as interleukin (IL)-17A/F, IL-23, and IL-17RA in psoriasis and IL-13 and IL-4Rα in atopic dermatitis. However, oral therapy is still preferred by many patients owing to the ease of use and needle-free administration. Phosphodiesterase 4 (PDE4) inhibitors have been approved for both oral and topical use for inflammatory skin diseases. In this review, we present a summary of an emerging class of selective PDE4B/D inhibitors under clinical development and compare the differences in selectivity of this new generation of PDE4 inhibitors with the less selective currently approved PDE4 inhibitors.