Phosphodiesterases (PDEs) are enzymes that degrade the second messengers cAMP and cGMP, influencing processes like cell proliferation, apoptosis, inflammation, and immune response. With 11 isoenzyme groups and 50 isoforms, PDEs regulate intracellular signaling and are involved in diseases such as COPD, depression, diabetes, and inflammatory conditions like inflammatory bowel diseases (IBD) and psoriatic arthritis (PsA). IBD and PsA share immune dysregulation and the IL-23/IL-17 axis, often overlapping with enteropathic spondyloarthritis (eSpA), which connects gut and joint diseases. This has led to multidisciplinary approaches to improve diagnosis and treatment.

Apremilast, an oral PDE4 inhibitor, effectively treats PsA by modulating inflammatory mediators like TNF, IL-17, and IFN-γ, while promoting regulatory cytokines like IL-10. It has a good safety profile in clinical trials and real-life settings. Apremilast has also shown clinical and endoscopic improvements in patients with ulcerative colitis, though clinical remission was not fully achieved. In PsA, it significantly improved disease markers such as ACR20, ACR50, and ACR70, with long-term benefits. Apremilast has also been effective in treating skin manifestations and extra-articular symptoms like enthesitis and dactylitis in PsA, making it a valuable option for managing both PsA and eSpA.

Reference: Picchianti-Diamanti A, Spinelli FR, Rosado MM, Conti F, Laganà B. Inhibition of Phosphodiesterase-4 in Psoriatic Arthritis and Inflammatory Bowel Diseases. Int J Mol Sci. 2021 Mar 5;22(5):2638. doi: 10.3390/ijms22052638. PMID: 33807944; PMCID: PMC7961737.