Analysis of the mechanism and principle of action of Apremilast (Otelor) in the treatment of psoriasis

Apremilast is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor, which is widely used in the treatment of moderate to severe psoriasis and psoriatic arthritis. Its mechanism of action is based on the regulation of inflammatory signaling pathways. It regulates intracellular cyclic adenosine monophosphate (cAMP) levels by inhibiting PDE4 activity, thereby exerting anti-inflammatory and immunoregulatory effects. PDE4 is the main cAMP degrading enzyme in inflammatory cells and plays an important role in the immunopathological process of psoriasis. It is especially highly expressed in T cells, monocytes and dendritic cells.

Apremilast increases intracellular cAMP levels by inhibiting the activity of PDE4 . cAMP is an important secondary messenger that can regulate protein kinase A (PKA ) activity and inhibit nuclear factor through the PKA pathway Activation of the κB (NF-κB) signaling pathway. NF-κB is a pro-inflammatory cytokine in psoriatic skin lesions such as TNF-α, IL-23, IL-17, IL-6 and other important regulators of expression. By inhibiting the activation of NF-κB , apremilast can significantly reduce the secretion of pro-inflammatory cytokines, thereby alleviating the excessive proliferation and inflammatory response of keratinocytes.

In addition, apremilast can also upregulate the expression of anti-inflammatory cytokines such as IL-10 through cAMP signaling. IL-10 It has the effect of inhibiting immune response and reducing inflammatory damage, and plays a negative regulatory role in the pathological mechanism of psoriasis. By increasing IL-10 levels, apremilast not only inhibits the excessive release of inflammatory mediators, but also helps restore skin immune homeostasis and improve clinical manifestations such as erythema, scale, and thickening of psoriatic plaques. At the same time, apremilast also has a certain inhibitory effect on the activation of dendritic cells, thereby reducing the impact on T Abnormal stimulation of cells reduces skin inflammation levels.

At the system level, the mechanism of apremilast is reflected in the two-way regulation of Th1 and Th17 immune responses. The activity of Th17 cells in patients with psoriasis is significantly enhanced, secreting IL-17, IL-22 and other pro-inflammatory factors, leading to abnormal proliferation of keratinocytes. Apremilast inhibits the activation and secretion function of Th17 cells by increasing cAMP and inhibiting the release of IFN-γ by Th1 cells, thereby overall reducing the inflammatory load of the skin. Its oral small molecule properties also enable the drug to be evenly distributed in the body, and also have a certain regulatory effect on systemic inflammatory responses.

Clinical data further confirmed the consistency of apremilast's mechanism of action and efficacy. Patients can see a reduction in rashes, itching, and scaling within weeks of treatment, and results are maintained and quality of life improved with long-term use. Compared with traditional immunosuppressants, apremilast does not require frequent monitoring of hematology or liver and kidney functions, is better tolerated, and is patient compliance-friendly. This also shows that its mechanism of accurately regulating inflammatory signals is operable and safe in clinical practice.

In summary, apremilast selectively inhibits PDE4, increases intracellular cAMP levels, and regulates NF-κB Signaling and pro-inflammatory /The balance of anti-inflammatory cytokines enables precise intervention in the immune and inflammatory pathways of psoriasis. Its principle of action covers signal regulation at the cellular level, suppression of immune cell activity, and reduction of systemic inflammatory load, allowing patients to relieve skin symptoms while maintaining good long-term safety. This mechanism of apremilast not only provides a scientific basis for the oral treatment of psoriasis, but also provides an important reference for future drug development for immune inflammatory diseases.

Reference materials:https://www.ema.europa.eu/en/homepage