Abstract
Background. In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets. The novel Phosphodiesterase 4 (PDE4) inhibitors have been recently introduced as new modulators of intracellular signals and gene transcription for the treatment of IBD. Aim. To discuss and describe the state of the art of this new class of compounds in the IBD field, with particular attention to apremilast. Methods. Published articles selected from PubMed were comprehensively reviewed, with key words including apremilast, inflammatory disease, IBD, psoriasis, psoriatic arthritis, pathogenesis, therapies, and treatment. Results. PDE4 inhibitors generate elevated intracellular levels of cyclic Adenosine Monophosphate (cAMP), that consequently down-regulate the release of pro-inflammatory cytokines in the mucosa of IBD patients. The newly developed apremilast is one of these drugs and has already been approved for the treatment of dermatologic/rheumatologic inflammatory conditions; studies in psoriasis and psoriatic arthritis have in fact demonstrated its clinical activity. However, no clinical trials have yet been published on the use of apremilast in IBD. Conclusion. In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy also in IBD.
Highlights
Inflammatory Bowel Diseases (IBD) are chronic, progressive, and relapsing disorders involving the human gut
This review aims to analyze the mechanisms of action of Phosphodiesterase 4 (PDE4) inhibitors and to describe the state of the art of apremilast and its similar compounds for the treatment of various inflammatory conditions; we will focus our attention on apremilast and on how its clinical efficacy in patients with Psoriasis and Psoriatic Arthritis (PsA), may be translated in IBD
Elevated intracellular cyclic Adenosine Monophosphate (cAMP) levels generated by PDE4 inhibitors lead to downregulation of the inflammatory response by modulating the expression of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB), Tumor Necrosis Factor (TNF)-α, IL-1β, IL-17, and other pro-inflammatory molecules found to be released in the mucosa of patients with IBD
Summary
Inflammatory Bowel Diseases (IBD) are chronic, progressive, and relapsing disorders involving the human gut. In spite of a wider spectrum of biological drugs, a significant proportion of patients are unaffected by or lose their response to these molecules [5,6,7,8,9,10,11], along with increased risks of infections and malignancies [12,13] For these reasons there is an urgent need to look for new pharmacological targets. In spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy in IBD
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